Article

Geidd JN. Structural magnetic resonance imaging of the adolescent brain. Ann N Y Acad Sci 1021: 77-85

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Abstract

Magnetic resonance imaging (MRI) provides accurate anatomical brain images without the use of ionizing radiation, allowing longitudinal studies of brain morphometry during adolescent development. Results from an ongoing brain imaging project being conducted at the Child Psychiatry Branch of the National Institute of Mental Health indicate dynamic changes in brain anatomy throughout adolescence. White matter increases in a roughly linear pattern, with minor differences in slope in the four major lobes (frontal, parietal, temporal, occipital). Cortical gray matter follows an inverted U-shape developmental course with greater regional variation than white matter. For instance, frontal gray matter volume peaks at about age 11.0 years in girls and 12.1 years in boys, whereas temporal gray matter volume peaks at about age at 16.7 years in girls and 16.2 years in boys. The dorsal lateral prefrontal cortex, important for controlling impulses, is among the latest brain regions to mature without reaching adult dimensions until the early 20s. The details of the relationships between anatomical changes and behavioral changes, and the forces that influence brain development, have not been well established and remain a prominent goal of ongoing investigations.

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... However, little is known about how aperiodic activity changes during the adolescent period, a developmental period during which we know that subdivisions of the brain undergo substantial structural refinement, most notably protracted maturation trajectories in prefrontal cortical regions relative to cortical and subcortical limbic and striatal regions associated with affect and motivated states (Blakemore, 2012;Blakemore and Choudhury, 2006;Casey et al., 2000;Cao et al., 2017;Dosenbach et al., 2010;Goddings et al., 2014;Mills et al., 2016;Paus, 2005;Segalowitz et al., 2010). Sexual dimorphism in human brain development is also well documented, with girls showing earlier brain maturation patterns when compared to boys of similar age (Blakemore, 2012;Dennison et al., 2013;Giedd, 2004;Giedd et al., 1996;Lenroot et al., 2007;Neufang et al., 2008;Sowell et al., 2001). However, to the best of our knowledge, no longitudinal study has investigated how developmental trajectories in aperiodic activity may differ between male and female participants during early adolescence. ...
... We also hypothesized that male participants would show greater offset and exponent magnitudes when compared to female participants. This hypothesis is based on prior research showing sexual dimorphism in human brain development (Blakemore, 2012;Dennison et al., 2013;Giedd, 2004;Giedd et al., 1996;Lenroot et al., 2007;Neufang et al., 2008;Sowell et al., 2001). As an additional exploratory step, we also investigated whether a measure of pubertal development explained any interactions found between sex and age. ...
... Therefore, it is possible that maturational changes in the aperiodic offset as measured in scalp EEG may well reflect underlying morphological change, with such changes in cortical thickness/volume occurring during early-to mid-adolescence. In fact, total cerebral grey matter volume appears to decline from its maximal level between approximately 7-12 years of age (Giedd et al., 1999;Mills et al., 2016;Sowell et al., 2001) and continues to decrease post-puberty into late adolescence and young adulthood (Giedd et al., 1999;Giedd, 2004;Gogtay et al., 2004;Lenroot et al., 2007;Paus, 2005). ...
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Aperiodic activity contains important and meaningful physiological information that has been shown to dynamically change with age. However, no longitudinal studies have examined its development during early-to-mid adolescence. The current study closes this gap by investigating age- and sex-related longitudinal change in aperiodic activity across early-to-mid adolescence (N = 186; 54.3% female). Participants completed a resting state task and a Flanker task while EEG was record at age 13 years and again at age 15 years. Across different tasks and two time points, we observed significant age-related reductions in aperiodic offset and exponent. In addition, we observed significant sex-related differences in the aperiodic offset and exponent over time. We did not find any significant correlation between aperiodic activity and behavioral measures, nor did we find any significant condition-dependent change in aperiodic activity during the Flanker task. However, we did observe significant correlations between aperiodic activity across tasks and over time, suggesting that aperiodic activity may demonstrate stable trait-like characteristic. Collectively, these results may suggest a developmental parallelism between decreases in aperiodic components alongside adolescent brain development during this period; changes to cortical and subcortical brain structure and organization during early adolescence may have been responsible for the observed sex-related effects.
... The human brain undergoes profound changes over the entire life span [1]. Starting from childhood, gray matter volume declines [2], in part reflecting synaptic pruning [3], while white matter volume increases, contributing to efficient neural signaling and transmission [2]. The marked morphological development, along with the maturation in microstructural fiber pathways [4], gives rise to the remodeling of functional brain circuits, supporting the capacity for high-level cognition [5]. ...
... The human brain undergoes profound changes over the entire life span [1]. Starting from childhood, gray matter volume declines [2], in part reflecting synaptic pruning [3], while white matter volume increases, contributing to efficient neural signaling and transmission [2]. The marked morphological development, along with the maturation in microstructural fiber pathways [4], gives rise to the remodeling of functional brain circuits, supporting the capacity for high-level cognition [5]. ...
... Now, we define the canonical variables p x and p y as being linked to a single factor α k if τ x and τ y are orthogonal to all components except for u k and v k , such that p x = τ x ⊤ x = τ x ⊤ Uα = τ x ⊤ u k α k ∝ α k , and likewise, p y ∝ α k . (2) In practice, the above condition cannot be guaranteed in the CCA setting as α cannot be uniquely determined. In fact, for any orthogonal transformation R, one can re-define the generative procedure with respect to α′ = Rα as x = Uα = UR ⊤ Rα = U′α′, and likewise, y = V ′α′ . ...
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Starting from childhood, the human brain restructures and rewires throughout life. Characterizing such complex brain development requires effective analysis of longitudinal and multi-modal neuroimaging data. Here, we propose such an analysis approach named Longitudinal Correlation Analysis (LCA). LCA couples the data of two modalities by first reducing the input from each modality to a latent representation based on autoencoders. A self-supervised strategy then relates the two latent spaces by jointly disentangling two directions, one in each space, such that the longitudinal changes in latent representations along those directions are maximally correlated between modalities. We applied LCA to analyze the longitudinal T1-weighted and diffusion-weighted MRIs of 679 youths from the National Consortium on Alcohol and Neurodevelopment in Adolescence. Unlike existing approaches that focus on either cross-sectional or single-modal modeling, LCA successfully unraveled coupled macrostructural and microstructural brain development from morphological and diffusivity features extracted from the data. A retesting of LCA on raw 3D image volumes of those subjects successfully replicated the findings from the feature-based analysis. Lastly, the developmental effects revealed by LCA were inline with the current understanding of maturational patterns of the adolescent brain.
... Adolescence is a period of critical development of the brain, characterized by changes in both structure (1)(2)(3)(4) and function (5,6) that coincide with changes in cognition and behavior (7). It is also a time of increasing incidence of many psychiatric disorders, including depression, which occurs more frequently in females than males (8,9). ...
... A total of 520 analyzable fMRI scans were available for N = 298 healthy participants, aged 14 to 26 years, each scanned one to three times as part of an accelerated longitudinal study of adolescent brain development [Neuroscience in Psychiatry Network (NSPN); see the "Data" section in Supplementary Text] (1,2,6,14,38). Participants self-identified their sex as either male or female. ...
Article
Sexual differences in human brain development could be relevant to sex differences in the incidence of depression during adolescence. We tested for sex differences in parameters of normative brain network development using fMRI data on N = 298 healthy adolescents, aged 14 to 26 years, each scanned one to three times. Sexually divergent development of functional connectivity was located in the default mode network, limbic cortex, and subcortical nuclei. Females had a more “disruptive” pattern of development, where weak functional connectivity at age 14 became stronger during adolescence. This fMRI-derived map of sexually divergent brain network development was robustly colocated with i prior loci of reward-related brain activation ii a map of functional dysconnectivity in major depressive disorder (MDD), and iii an adult brain gene transcriptional pattern enriched for genes on the X chromosome, neurodevelopmental genes, and risk genes for MDD. We found normative sexual divergence in adolescent development of a cortico-subcortical brain functional network that is relevant to depression.
... Adolescents may respond differently to cannabis exposure compared to adults. Adolescence is an important period of neurodevelopment, during which neural connections are selectively pruned and strengthened in an experience-driven manner [4,5]. The endocannabinoid system, the primary neurobiological target of cannabis, is thought to play a central role in this development, and is itself an important target of neuromaturation during adolescence [6]. ...
... Therefore, many researchers have suggested that adolescence is a sensitive period for the potentially adverse effects of cannabis and other drugs [7][8][9]. Brain maturation during adolescence coincides temporally with key milestones in cognitive development [4,10]. Anatomical differences between adult and adolescent samples are pronounced in frontal and striatal regions, which are important to reward and motivation [11]. ...
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Chronic use of drugs may alter the brain’s reward system, though the extant literature concerning long-term cannabis use and neural correlates of reward processing has shown mixed results. Adolescents may be more vulnerable to the adverse effects of cannabis than adults; however, this has not been investigated for reward processing. As part of the ‘CannTeen’ study, in the largest functional magnetic resonance imaging study of reward processing and cannabis use to date, we investigated reward anticipation and feedback in 125 adult (26–29 years) and adolescent (16–17 years) cannabis users (1–7 days/week cannabis use) and gender- and age-matched controls, using the Monetary Incentive Delay task. Blood-oxygen-level-dependent responses were examined using region of interest (ROI) analyses in the bilateral ventral striatum for reward anticipation and right ventral striatum and left ventromedial prefrontal cortex for feedback, and exploratory whole-brain analyses. Results showed no User-Group or User-Group × Age-Group effects during reward anticipation or feedback in pre-defined ROIs. These null findings were supported by post hoc Bayesian analyses. However, in the whole-brain analysis, cannabis users had greater feedback activity in the prefrontal and inferior parietal cortex compared to controls. In conclusion, cannabis users and controls had similar neural responses during reward anticipation and in hypothesised reward-related regions during reward feedback. The whole-brain analysis revealed tentative evidence of greater fronto-parietal activity in cannabis users during feedback. Adolescents showed no increased vulnerability compared with adults. Overall, reward anticipation and feedback processing appear spared in adolescent and adult cannabis users, but future longitudinal studies are needed to corroborate this.
... De manière parallèle, le volume de matière blanche continue d'augmenter avec l'âge (voir Tau & Peterson, 2010, pour revue), sa production croissant considérablement pendant l'adolescence (Lu & Sowell, 2009) (cf. Figure 6). La myélinisation permet l'accélération et l'amplification de la transmission de l'information sur de longues distances (Giedd, 2004(Giedd, , 2008Gogtay et al., 2004;Tomas Paus et al., 1999). ...
... L'une des questions critiques est de savoir si les modifications cérébrales engendrées par un entraînement et décrites ci-dessus sont similaires à tous les âges. Nous avons vu dans le précédent chapitre que le volume de matière grise diminuait naturellement durant la fin de l'enfance et l'adolescence (Giedd, 2004;Gogtay et al., 2004;Sowell, Thompson, Tessner, & Toga, 2001;Sowell et al., 2003). En revanche, les études sur l'entrainement ont mis en évidence une augmentation de la matière grise lorsque des adultes apprenaient à jongler , lorsqu'ils étudiaient pour un examen (Draganski et al., 2006) ou bien lorsqu'ils apprenaient la lecture en miroir (Ilg et al., 2008). ...
Thesis
Les fonctions exécutives (FE), et en particulier le Contrôle Inhibiteur (CI), jouent un rôle très important dans la réussite académique et professionnelle ainsi que dans la physiopathologie de nombreux troubles psychiatriques. L'adolescence est une période critique du développement du CI, ce dernier étant sous-tendu en particulier par la maturation tardive du cortex préfrontal jusqu’au début de l'âge adulte. Le premier objectif de cette thèse a été de cartographier les bases neurales du CI durant le développement et d'en évaluer leurs spécificités en les comparant avec celles de la mémoire de travail (MdT), une autre composante clef des FE. À partir d'une méta-analyse des études en IRMf du CI et de la MdT incluant 845 enfants, 1377 adolescents et 10235 adultes, nous avons identifié des modifications de l'activité fonctionnelle, à savoir le passage d'un réseau diffus à un réseau focal plus spécialisé avec l'âge, en accord avec un modèle dynamique du développement cérébral. Un large recouvrement de régions fronto-pariétales pour le CI et la MdT a également été détecté, ce qui soulève la question de la spécificité des processus et des tâches de ces deux FE. Par la suite, nous avons analysé l'effet à long terme du neuro-développement précoce sur le CI à partir de l'étude de la morphologie sulcale, un paramètre anatomique du cerveau déterminé lors de la vie fœtale. Dans un premier temps, nous avons montré, d'après une analyse longitudinale de 243 IRM, la stabilité du motif des sillons durant le développement. Nous avons par la suite établi que les polymorphismes sulcaux du cortex cingulaire antérieur et du sillon frontal inférieur contribuaient, de manière complémentaire, à l'efficience du CI chez l'enfant et également chez l'adulte. Enfin, nous nous sommes intéressés à l’entraînement cognitif au CI à l'adolescence, une période de très grande plasticité cérébrale et de sensibilité à l'environnement. Nous avons étudié chez 49 adolescents de 16-17 ans l'effet d'un entraînement intensif sur tablette tactile (25 sessions de 15 minutes par jour) au CI versus Contrôle Actif aux niveaux cognitif et cérébral (IRMf : tâches de stop-signal, de matrice de points, du réseau attentionnel et de gratification retardée). Nous avons en particulier évalué l'effet des facteurs neurodéveloppementaux précoces sur la réceptivité à l’entraînement au CI. Ces travaux s'inscrivent dans un nouveau champ de recherche interdisciplinaire à l'interface entre les neurosciences et la psychologie. Dans une perspective translationnelle éducative et thérapeutique, il vise à évaluer le plus finement possible, grâce à l'imagerie cérébrale anatomique et fonctionnelle, quelles interventions pédagogiques et thérapeutiques sont susceptibles d'aider au mieux le cerveau à surmonter des difficultés d'ordre cognitif.
... Adolescence, the period of ∼12-20 years old in humans and from weaning [postnatal day (PND) 21] to ∼8 weeks in rodents, is characterized by high levels of playful social interactions, cognitive development, and increased risk-taking behaviors (Spear, 2000). During this period, brain volume and white matter increase linearly with age (Giedd et al., 1999;Sowell et al., 2002;Giedd, 2004) until age 20 (Pfefferbaum et al., 1994). In the prefrontal cortex (PFC), neurons also undergo dramatic structural reorganization and synaptic remodeling (Giedd, 2004). ...
... During this period, brain volume and white matter increase linearly with age (Giedd et al., 1999;Sowell et al., 2002;Giedd, 2004) until age 20 (Pfefferbaum et al., 1994). In the prefrontal cortex (PFC), neurons also undergo dramatic structural reorganization and synaptic remodeling (Giedd, 2004). In the prefrontal and orbitofrontal cortexes, up to 50% of spines are pruned from early to mid-adolescence (Bourgeois et al., 1994;Huttenlocher and Dabholkar, 1997;Shapiro et al., 2017). ...
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Adolescence is a critical developmental period characterized by enhanced social interactions, ongoing development of the frontal cortex and maturation of synaptic connections throughout the brain. Adolescents spend more time interacting with peers than any other age group and display heightened reward sensitivity, impulsivity and diminished inhibitory self-control, which contribute to increased risky behaviors, including the initiation and progression of alcohol use. Compared to adults, adolescents are less susceptible to the negative effects of ethanol, but are more susceptible to the negative effects of stress, particularly social stress. Juvenile exposure to social isolation or binge ethanol disrupts synaptic connections, dendritic spine morphology, and myelin remodeling in the frontal cortex. These structural effects may underlie the behavioral and cognitive deficits seen later in life, including social and memory deficits, increased anxiety-like behavior and risk for alcohol use disorders (AUD). Although the alcohol and social stress fields are actively investigating the mechanisms through which these effects occur, significant gaps in our understanding exist, particularly in the intersection of the two fields. This review will highlight the areas of convergence and divergence in the fields of adolescent social stress and ethanol exposure. We will focus on how ethanol exposure or social isolation stress can impact the development of the frontal cortex and lead to lasting behavioral changes in adulthood. We call attention to the need for more mechanistic studies and the inclusion of the evaluation of sex differences in these molecular, structural, and behavioral responses.
... The induced current signal is received by the radiofrequency receiving coil and recorded, and eventually the image can be reconstructed by signal processing and image reconstruction algorithms. Fine-tuning the parameters (e.g. the flip angle or the pulse interval) lead to a variety of MRI sequences, such as T1w, T2w, and T2w-FLAIR MRI, and each sequence highlights different tissues of the brain, such as gray matter or white matter (Giedd, 2004). Specifically, T1w MRI maps the anatomical structure of the brain; T2w MRI captures the aberrant zone in the white matter; T2w-FLAIR MRI provides high contrasts between the gray matter and cerebrospinal fluid (CSF). ...
... The polynomial kernel is popular in image processing. Many extensions and variants of SVMs have been proposed for the versatility of SVMs, such as, one-class SVM (OC-SVM) (Schölkopf et al., 1999), least square SVM (LS-SVM) (Suykens and Vandewalle, 2004;Suykens et al., 2002;Liu et al., 2016), fuzzy SVM (Lin and Wang, 2002, 2004, weighted SVM (Yang et al., 2005), transductive SVM (Cevikalp and Franc, 2017), and twin SVM (Jayadeva et al., 2007). They significantly facilitate the classification of neuroimaging. ...
Article
Machine learning is playing an increasingly important role in medical image analysis, spawning new advances in the clinical application of neuroimaging. There have been some reviews on machine learning and epilepsy before, and they mainly focused on electrophysiological signals such as electroencephalography (EEG) and stereo electroencephalography (SEEG), while neglecting the potential of neuroimaging in epilepsy research. Neuroimaging has its important advantages in confirming the range of the epileptic region, which is essential in presurgical evaluation and assessment after surgery. However, it is difficult for EEG to locate the accurate epilepsy lesion region in the brain. In this review, we emphasize the interaction between neuroimaging and machine learning in the context of epilepsy diagnosis and prognosis. We start with an overview of epilepsy and typical neuroimaging modalities used in epilepsy clinics, MRI, DWI, fMRI, and PET. Then, we elaborate two approaches in applying machine learning methods to neuroimaging data: i) the conventional machine learning approach combining manual feature engineering and classifiers, ii) the deep learning approach, such as the convolutional neural networks and autoencoders. Subsequently, the application of machine learning on epilepsy neuroimaging, such as segmentation, localization, and lateralization tasks, as well as tasks directly related to diagnosis and prognosis are looked into in detail. Finally, we discuss the current achievements, challenges, and potential future directions in this field, hoping to pave the way for computer-aided diagnosis and prognosis of epilepsy.
... Adolescence is a critical time of neurodevelopment. The adolescent brain undergoes periods of rapid growth, structural reorganization, and neurogenesis/neuronal pruning [11]. Alcohol (and other drugs of abuse) alters the normal neuronal developmental processes. ...
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A consistent preclinical finding is that exposure to alcohol during adolescence produces a persistent hyperdopaminergic state during adulthood. The current experiments determine that effects of Adolescent Intermittent Ethanol (AIE) on the adult neurochemical response to EtOH administered directly into the mesolimbic dopamine system, alterations in dendritic spine and gene expression within the nucleus accumbens shell (AcbSh), and if treatment with the HDACII inhibitor TSA could normalize the consequences of AIE. Rats were exposed to the AIE (4 g/kg ig; 3 days a week) or water (CON) during adolescence, and all testing occurred during adulthood. CON and AIE rats were microinjected with EtOH directly into the posterior VTA and dopamine and glutamate levels were recorded in the AcbSh. Separate groups of AIE and CON rats were sacrificed during adulthood and Taqman arrays and dendritic spine morphology assessments were performed. The data indicated that exposure to AIE resulted in a significant leftward and upward shift in the dose-response curve for an increase in dopamine in the AcbSh following EtOH microinjection into the posterior VTA. Taqman array indicated that AIE exposure affected the expression of target genes (Chrna7, Impact, Chrna5). The data indicated no alterations in dendritic spine morphology in the AcbSh or any alteration in AIE effects by TSA administration. Binge-like EtOH exposure during adolescence enhances the response to acute ethanol challenge in adulthood, demonstrating that AIE produces a hyperdopaminergic mesolimbic system in both male and female Wistar rats. The neuroadaptations induced by AIE in the AcbSh could be part of the biological basis of the observed negative consequences of adolescent binge-like alcohol exposure on adult drug self-administration behaviors.
... Neuroimaging studies examining the effects of lifetime co-use on GM integrity are a point of contention as studies suggest cannabis may protect against the detrimental effects of alcohol use. Prior research has shown that GM volume typically increases in early childhood followed by post-adolescent decreases [51,52]; however, longitudinal work found that adolescent alcohol users show substantial, problematic decreases in GM surface area in the orbital frontal cortex compared to lifetime co-users [40•]. Damage to this region in the frontal lobes is associated with greater impulsivity and risk-taking behavior [53] and decreases in GM surface area among alcohol users may place them at greater risk for associated outcomes. ...
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Purpose of Review Given increases in the rates of alcohol and cannabis co-use among adolescents and young adults, this review aims to summarize literature on the effects of alcohol and cannabis co-use on neurocognitive functioning, brain structure, and brain function. Recent Findings The limited existing studies examining concurrent, recent, and lifetime alcohol and cannabis co-use suggest effects on the brain are likely multifaceted. The majority of studies report that co-use is associated with negative outcomes such as impaired cognitive function and significant alterations in key structural and functional regions of the brain, while others report null effects of co-use compared to non-substance using control and single-substance use groups. Summary Current studies lack a general consensus on methodology, definitions of concurrent and simultaneous use, and neuroimaging approaches, which makes it challenging to draw strong conclusions about the effects of co-use. More studies are needed to explore the effects of co-use in the context of simultaneous alcohol and cannabis use.
... Structural MRI (s-MRI) scans are used to examine anatomy and neurology of the brain. s-MRI scans are also employed to measure the volume of brain, i.e. regional gray matter (GM), white matter (WM) and cerebrospinal fluid (CSF) (Giedd 2004), and volume of its sub-regions and to identify localized lesions (Budman, Hoyt, and Friedman 1992). Functional MRI (f-MRI) scans are used to visualize the activated brain regions associated with brain function. ...
Article
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Autism Spectrum Disorder (ASD) is linked with abridged ability in social behavior. Scientists working in the broader domain of cognitive sciences have done a lot of research to discover the root cause of ASD, but its biomarkers are still unknown. Some studies from the domain of neuroscience have highlighted the fact that corpus callosum and intracranial brain volume hold significant information for the detection of ASD. Taking inspiration from such findings, in this article, we have proposed a machine learning based framework for automatic detection of ASD using features extracted from corpus callosum and intracranial brain volume. Our proposed framework has not only achieved good recognition accuracy but has also reduced the complexity of training machine learning model by selecting features that are most significant in terms of discriminative capabilities for classification of ASD. Second, for benchmarking and to verify potential of deep learning on analyzing neuroimaging data, in this article, we have presented results achieved by using the transfer learning approach. For this purpose, we have used the pre-trained VGG16 model for the classification of ASD.
... Although it is well known that frontal brain regions continue to develop during adolescence (Blakemore, 2008;Casey et al., 2008;Giedd, 2004) and that these processes underpin the development of social and cognitive skills that are often impaired in psychosis, there are also important brain changes that occur during early and middle childhood, as well as changes in early adolescence that are often associated with hormonal differences between boys and girls (Blakemore et al., 2010;Gogtay et al., 2004;Peper & Dahl, 2013). Given that various brain regions show differential trajectories of development that may also be sex-dependent, this review has highlighted potentially critical biases toward the inclusion of older participants (i.e., late adolescence and early adulthood), with little attention to potential sex differences, in existing studies of the neural correlates of schizotypy. ...
Article
Schizotypy refers to a multidimensional construct that spans a range of cognitive, behavioral, and personality features, representing liability to psychosis on a continuum between health and illness. Schizotypy has been associated with functional and structural brain alterations as potential intermediate phenotypes on the developmental path to psychosis. We scanned the literature between February 2019 and August 1, 2020 using PubMed, Medline, APA PsycINFO, and ProQuest. We identified eligible articles conducted on participants assessed with psychometric schizotypy across the health-illness spectrum and reporting a direct statistic between schizotypy and a structural, task-related, or functional magnetic resonance imaging brain measure. Articles not peer-reviewed and not written in English were excluded. We systematically reviewed 84 studies that determined the changes in gray matter, brain activation, and connectivity associated with schizotypy in both healthy and clinical cohorts. Morphological and functional changes in the default and the frontoparietal networks, specifically frontal and temporal cortices, were most frequently associated with schizotypy. Yet, we were unable to identify consistent patterns of morphological or functional brain aberration associated with schizotypy, due to methodological differences between studies in the conceptualization and measurement of schizotypy. Efforts toward greater methodological concordance in future neuroimaging research of schizotypy are needed to improve the identification of brain-based endophenotypes for schizophrenia.
... There is no validated youth head model; therefore, the GHBMC model was scaled to linear dimensions of 95.83% (88% of the volume), representing a 13year-old female 48 and was determined from head volume differences between sexes. 19,[48][49][50][51][52][53] Specific details are presented in the primary GHBMC description. 47 A commercially available software (LS-DYNA; Livermore Software Technology Co., Livermore, CA) was used to run the simulations with an 8-core processer. ...
Article
Head impacts in soccer have been associated with both short- and long-term neurological consequences. Youth players' brains are especially vulnerable given that their brains are still developing, and females are at an increased risk of traumatic brain injury (TBI) compared to males. Approximately 90% of head impacts in soccer occur from purposeful heading. Accordingly, this study assessed the relationship between kinematic variables and brain strain during purposeful headers in female youth soccer players. A convenience sample of 36 youth female soccer players (13.4 [0.9] years of age) from three elite youth soccer teams wore wireless sensors to quantify head impact magnitudes during games. Purposeful heading events were categorized by game scenario (e.g., throw-in, goal kick) for 60 regular season games (20 games per team). A total of 434 purposeful headers were identified. Finite element model simulations were performed to calculate average peak maximum principal strain (APMPS) in the corpus callosum, thalamus, and brainstem on a subset of 110 representative head impacts. Rotational velocity was strongly associated with APMPS in these three regions of the brain (r = 0.83-0.87). Linear acceleration was weakly associated with APMPS (r = 0.13-0.31). Game scenario did not predict APMPS during soccer games (p > 0.05). Results demonstrated considerable APMPS in the corpus callosum (mean = 0.102) and thalamus (mean = 0.083). In addition, the results support the notion that rotational velocity is a better predictor of brain strain than linear acceleration and may be a potential indicator of changes to the brain.
... Vulnerability is also significant in limbic system (Peper et al. 2011). Neurotransmission and synaptic plasticity in adolescence can be influenced also by nutrition, substance abuse and neurochemical stressors that can be produced during diseases, particularly psychiatric diseases (Giedd 2004). Abnormal neurotransmission can trigger an excess in pruning of synaptic contacts in adolescence, which can lead to reduction in GM (Uhlhaas 2011, Gogtay et al. 2011, while the late manifestation of schizophrenia can be the consequence of excessive synaptic elimination during adolescence (Peter 1979). ...
Article
Background: Brain maturation is considered completed around the age of 25, when prefrontal cortex maturation has been achieved. The aim of our study was to investigate the alterations of grey matter (GM) in patients with the onset of schizophrenia before and after the completion of brain maturation. Subjects and methods: The study group included 100 schizophrenia patients, while the control group comprised 50 healthy individuals. Brain magnetic resonance imaging was acquired on a 1.5 T scanner. Voxel-based morphometry (VBM) analyses were performed between groups. Results: GM of the schizophrenic patients is reduced in many regions (p<0.005 FDR corrected). Most widespread reduction is detected in frontal cortex and cerebellum, the other regions being limbic cortex, insula, cuneus, precuneus, superior temporal gyrus and motor cortex. The decrease of grey matter volume (GMV) increases with the increase in number of psychotic episodes and is more pronounced in the patients with earlier onset of the disease. Conclusions: The age of the onset of the disease is important for both total and relative loss of GMV. Earlier onset of schizophrenia, prior to full brain maturation results in significant reduction of GM in comparison with healthy subjects and patients with later, post full brain maturation onset of the disease.
... The null result we observed may be related to the fact that our sample of adults was fairly young, with over half being less than 25 years of age. Structures in the PFC responsible for cognitive control and executive function continue maturing for several years after age 18 (Cohen et al., 2016;Giedd, 2004). By contrast, it is also possible that developmental differences in threat/safety discrimination during extinction recall occur earlier in middle childhood (Glenn et al., 2012;Michalska et al., 2016;Schiele et al., 2016), in which case, our sample of mostly early adolescents may have been too old to detect age differences. ...
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Few studies have examined threat generalization across development and no developmental studies have compared the generalization of social versus nonsocial threat, making it difficult to identify contextual factors that contribute to threat learning across development. The present study assessed youth and adults’ multivoxel neural representations of social versus nonsocial threat stimuli. Twenty adults (Mage = 25.7 ± 4.9) and 16 youth (Mage = 14.1 ± 1.7) completed two conditioning and extinction recall paradigms: one social and one nonsocial paradigm. Three weeks after conditioning, participants underwent a functional magnetic resonance imaging extinction recall task that presented the extinguished threat cue (CS+), a safety cue (CS−), and generalization stimuli (GS) consisting of CS−/CS+ blends. Across age groups, neural activity patterns and self‐reported fear and memory ratings followed a linear generalization gradient for social threat stimuli and a quadratic generalization gradient for nonsocial threat stimuli, indicating enhanced threat/safety discrimination for social relative to nonsocial threat stimuli. The amygdala and ventromedial prefrontal cortex displayed the greatest neural pattern differentiation between the CS+ and GS/CS−, reinforcing their role in threat learning and extinction recall. Contrary to predictions, age did not influence threat representations. These findings highlight the importance of the social relevance of threat on generalization across development.
... Second, the patients were adolescents. During this AOS= adolescent-onset schizophrenia, GFC= global-brain functional connectivity period, the synaptic pruning, white matter increasing and specific axonal pathways experiencing further growing and branching would result in enhanced FC performance (Giedd, 2004;Miguel-Hidalgo, 2013). Finally, the measures of MRI (for example, ROI-based MRI analysis) could influence the findings. ...
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Abnormal functional connectivity (FC) has been reported in drug-naive first-episode adolescent-onset schizophrenia (AOS) with inconsistent results due to differently selected regions of interest. The voxel-wise global-brain functional connectivity (GFC) analysis can help explore abnormal FC in an unbiased way in AOS. A total of 48 drug-naive first-episode AOS as well as 31 sex-, age- and education-matched healthy controls were collected. Data were subjected to GFC, correlation analysis and support vector machine analyses. Compared with healthy controls, the AOS group exhibited increased GFC in the right middle frontal gyrus (MFG), and decreased GFC in the right inferior temporal gyrus, left superior temporal gyrus (STG)/precentral gyrus/postcentral gyrus, right posterior cingulate cortex /precuneus and bilateral cuneus. After the Benjamini-Hochberg correction, significantly negative correlations between GFC in the bilateral cuneus and Trail-Making Test: Part A (TMT-A) scores (r=-0.285, p=0.049), between GFC in the left STG/precentral gyrus/postcentral gyrus and TMT-A scores (r=-0.384, p=0.007), and between GFC in the right MFG and the fluency scores (r=-0.335, p=0.020) in the patients. GFC in the left STG/precentral gyrus/postcentral gyrus has a satisfactory accuracy (up to 86.08%) in classifying patients from controls. AOS shows abnormal GFC in the brain areas of multiple networks, which bears cognitive significance. These findings suggest potential abnormalities in processing self-monitoring and sensory prediction, which further elucidate the pathophysiology of AOS.
... The hippocampus matures within the first three years of life yet changes in microstructure as a result of synaptic pruning continue to occur into adulthood (Gogtay et al. 2006). Development of prefrontal cortex is even more protracted, with substantial changes in cortical thickness occurring through adolescence (Giedd 2004, Ofen et al. 2007). Increased engagement of prefrontal cortex in episodic memory tasks occurs from childhood through adolescence, correlated with performance (Wendelken et al. 2011). ...
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The ability to prioritize valuable information is critical for the efficient use of memory in daily life. When information is important, we engage more effective encoding mechanisms that can better support retrieval. Here, we describe a dual-mechanism framework of value-directed remembering in which both strategic and automatic processes lead to differential encoding of valuable information. Strategic processes rely on metacognitive awareness of effective deep encoding strategies that allow younger and healthy older adults to selectively remember important information. In contrast, some high-value information may also be encoded automatically in the absence of intention to remember, but this may be more impaired in older age. These different mechanisms are subserved by different neural substrates, with left-hemisphere semantic processing regions active during the strategic encoding of high-value items, and automatic enhancement of encoding of high-value items may be supported by activation of midbrain dopaminergic projections to the hippocampal region. Expected final online publication date for the Annual Review of Psychology, Volume 73 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
... Throughout adolescence and young adulthood, brain areas related to higher level functions (e.g., prefrontal cortex) continue to mature and therefore, so do the cognitive faculties which rely on these structures (e.g., working memory, inhibitory control, attention) [11][12][13]. Moreover, research indicates that the brain is not fully developed until about age 25, particularly in males [14][15][16]. Coincidentally, for many teens, it is during this critical period of structural brain and cognitive development when they first begin practicing to drive. Simply put, teens are faced with learning a highly complex behavior (i.e., driving) which relies heavily on their immature cognitive faculties, and if not carried out safely, is a behavior that has real life or death consequences for them as well as others (i.e., their passengers, other drivers/passengers/ motorcyclist/pedalcyclists/pedestrians). ...
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Background The proportion of motor vehicle crash fatalities involving alcohol-impaired drivers declined substantially between 1982 and 1997, but progress stopped after 1997. The systemic complexity of alcohol-impaired driving contributes to the persistence of this problem. This study aims to identify and map key feedback mechanisms that affect alcohol-impaired driving among adolescents and young adults in the U.S. Methods We apply the system dynamics approach to the problem of alcohol-impaired driving and bring a feedback perspective for understanding drivers and inhibitors of the problem. The causal loop diagram (i.e., map of dynamic hypotheses about the structure of the system producing observed behaviors over time) developed in this study is based on the output of two group model building sessions conducted with multidisciplinary subject-matter experts bolstered with extensive literature review. Results The causal loop diagram depicts diverse influences on youth impaired driving including parents, peers, policies, law enforcement, and the alcohol industry. Embedded in these feedback loops are the physical flow of youth between the categories of abstainers, drinkers who do not drive after drinking, and drinkers who drive after drinking. We identify key inertial factors, discuss how delay and feedback processes affect observed behaviors over time, and suggest strategies to reduce youth impaired driving. Conclusion This review presents the first causal loop diagram of alcohol-impaired driving among adolescents and it is a vital first step toward quantitative simulation modeling of the problem. Through continued research, this model could provide a powerful tool for understanding the systemic complexity of impaired driving among adolescents, and identifying effective prevention practices and policies to reduce youth impaired driving.
... Occipital bunning is clearly related to brain development and size increase (Caspari, 2006;Trinkaus & LeMay, 1982). However, the brain reaches 90% of its adult size by age 6 years, with only a minor size increase in adolescents (Giedd, 2004;Giedd et al., 1996). Further, a recent study of human brain development showed that, although occipital lobe gray matter increases into adult stages, this amounts to only a ≈ 5 cc increase between ≈12 and 22 years in males, with females reaching the maximum amount of gray matter in the occipital lobe by ≈16 years (Giedd et al., 1999). ...
Article
This article provides an ontogenetically based comparative description of two immature occipital fragments from Baume Moula‐Guercy (MIS 5e) and examines their affinities to European and Middle Eastern Middle‐to‐Late Pleistocene (≈MIS 14–MIS ≈ 1) Homo. Description of the M‐S‐41 and M‐S‐61 occipital fragments (≈6–8 years) is based on observations of original fossils, casts, CT scans, literature descriptions, and virtual ectocranial and endocranial reconstructions. Our ontogenetically based sample represents a Preneanderthal‐Neanderthal group and a Homo sapiens group. These groups are subdivided into (1) Preneanderthals (≈MIS 14–9), Early Neanderthals (MIS 7–5e), and Late Neanderthals (MIS 5d‐3), and (2) Middle (MIS 5), Upper (MIS 3–1), and Late (MIS ≈ 1) Paleolithic H. sapiens. Measurements and developmental age determinations follow standard techniques. Based on the M‐S‐41/M‐S‐61 composite, the strongly convex upper occipital scale flattens into the vertical suprainiac fossa, as in immature Early Neanderthals. A doubled suprainiac fossa expressing a weakly developed bounding torus and pocking of the central region is typical of immature Neanderthals. The transverse torus is thickened medially, lacks significant lateral development, has a laterally placed protuberance, and is concave medially. A linear (triangular) tubercle, as opposed to an external occipital protuberance, is present. An occipital bun is absent. The occipital remains from Moula‐Guercy make a substantial contribution to the record of Neanderthal cranial evolution because immature Early Neanderthal occipitals are rare, fragmentary, and likely represent only two paleodemes (Krapina, La Chaise‐de‐Vouthon). The Moula‐Guercy occipital possesses characteristics well‐established in European Neanderthals by MIS 7, and it is most similar to the occipitals of other Early Neanderthals.
... The deficit in cognitive memory seen in the adulthood indicates that altered brain function at adolescent has a profound effect on the function of adult brain. The findings of this study were strengthened by the earlier reports of Nestle and Malenka (2004), Giedd (2004), Winters (2008), and Olawepo et al. (2017), that shows that drug abuse in adolescent enhances progression of neurodegenerative disorders at adulthood. Surprisingly our finding shows that the spatial memory was not affected in the treated animal when compared to the control. ...
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Adolescence is a critical period of development in mammals characterized by risk-taking and adventures. The study was designed to evaluate the effects of exposure to hyoscyamine fraction of Daturastramonium seeds at adolescence on the hippocampus of adult Wistar rats. Fresh seeds of D.stramonium were procured, macerated and fractionated using high-performance liquid chromatography (HPLC). Twelve (12) adolescent Wistar rats with an average weight of 150±0.02 grams of equal gender were used for the study. Equivalent body weight of normal saline and 800 mg/kgbwt of hyoscyamine fraction of D.stramonium were orally administered for three weeks, from postnatal days (PND) 21-42. At adulthood, the animals were tested for memory test using Morris water maze (MWM) and Novel object recognition test (NORT) paradigms. The data acquired were Effects of Exposure of Hippocampus in Adult Wistar Rats (Rattusnorvegicus) to hyoscyamine Fraction of Daturastramonium Seeds at Adolescence I. A. Tela, S. A. Musa, I. A. Iliya J. O. Nzalak, DUJOPAS 6 (3): 224-236, 2020 225 expressed as mean ± SEM. Student's-t-test and repeated measures ANOVA with Fisher's multiple comparisons post-hoc tests were used to obtain mean differences using Minitab 17 (LLC., U.K.) statistical package software. P< 0.05 were considered statistically significant. Significant difference in the exploration time (p = 0.047), but nostatistically significant difference was observed (p = 0.648) in the Morris water maze test between groups. The CA1 region of the treated group showed significant cytoplasmic vacuolations, hyperchromasia and necrosis. In conclusion, adolescent exposure to hyoscyamine fraction of D. stramonium induces impairment of hippocampal cognitive function which may predisposes progression of neurodegenerative diseases at adulthood.
... In fact, the remodeling of brain structures that are dependent on androgens (MacLusky et al., 2006) or estrogens (Galea et al., 2006) during puberty includes mechanisms of neurogenesis, apoptosis, sprouting, and axonal projections, together with an increase or reduction in the degree of dendritic arborization (Rakic et al., 1994) and changes in the myelination of nerve pathways. These actions can generate changes in the volume of the gray matter and white matter in the cortex cerebral, temporal lobe, dorsolateral prefrontal cortex, striatum, and other subcortical structures, as well as changes in ventricular volume in the brain (Giedd, 2004;Giedd and col., 1999;Gogtay and col., 2004;Sowell and col., 2002). ...
... Evidence suggests that in adolescents with multiple high-risk behaviours or those enrolled in addiction treatment, cooccurring substance and non-substance related psychiatric comorbidities are "the rule rather than the exception" (Adair, 2009). The period of rapid brain development during adolescence represents a particularly vulnerable developmental stage for the onset of both mental illness and substance use disorders, with each type of disorder having the potential to exacerbate the other (Giedd, 2004). For instance, multiple childhood-onset psychiatric disorders, including depression, anxiety and disruptive behaviour disorders have been shown to increase the risk of adolescent-onset substance use disorders (Burke et al., 1994, White et al., 2001, Bukstein, 2000. ...
... The primary limitation is that the T1w/T2w ratio is not a direct measure of intracortical myelin content but rather a proxy that has been shown to successfully map the myeloarchitectonic properties in adults and typically developing children. Other factors can also contribute to the T1w/T2w measure such as iron content, which affects MRI signal contrast (Fukunaga et al., 2010), head motion affecting image quality which can indirectly affect the accurate placement of the cortical surface, as well as maturation of the local white matter (e.g., Giedd, 2004). Given the rigorous quality assurance of all structural images and exclusion of scans with major motion artifacts or surface placement inaccuracies, and the use of gray/white CNR as a measure of the overall image quality (which did not account for significant variance in any of the analyses), head motion is unlikely to be a major contributor for the current results. ...
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Intracortical myelin is thought to play a significant role in the development of neural circuits and functional networks, with consistent evidence of atypical network connectivity in children with autism spectrum disorders (ASD). However, little is known about the development of intracortical myelin in the first years of life in ASD, during the critical neurodevelopmental period when autism symptoms first emerge. Using T1-weighted (T1w) and T2-weighted (T2w) structural magnetic resonance imaging (MRI) in 21 young children with ASD and 16 typically developing (TD) children, ages 1.5 to 5.5 years, we demonstrate the feasibility of estimating intracortical myelin in vivo using the T1w/T2w ratio as a proxy. The resultant T1w/T2w maps were largely comparable with those reported in prior T1w/T2w studies in typically developing children and adults, and revealed no group differences between TD children and those with ASD. However, differential associations between T1w/T2w and age were identified in several early myelinated regions (e.g., visual, posterior cingulate, precuneus cortices) in the ASD and TD groups, with age-related increase in estimated myelin content across the toddler and preschool years detected in TD children, but not in children with ASD. The atypical age-related effects in intracortical myelin, suggesting a disrupted myelination in the first years of life in ASD, may be related to the aberrant brain network connectivity reported in young children with ASD in some of the same cortical regions and circuits. This article is protected by copyright. All rights reserved.
... Cannabis use has been associated with greater impulsivity (Clark, Roiser, Robbins, & Sahakian, 2009), and a systematic review by Pacheco-Colón, Limia, and Gonzalez (2018) found some evidence for a causal link between cannabis use and reduced motivation. Adolescents may be particularly vulnerable to the harmful effects of cannabis, including disrupted reward processing, due to the important frontal and limbic neuromaturation occurring during this time (Bossong & Niesink, 2010;Giedd, 2004;Giedd et al., 1999;Lubman, Cheetham, & Yücel, 2015;Schneider, 2008). Indeed, in another review, Pacheco-Colón, Ramirez, and Gonzalez (2019) found that adolescent cannabis use was strongly associated with academic outcomes and depression, but there was insufficient evidence to conclude whether cannabis use negatively impacted motivation in this age group. ...
Article
Cannabis use has historically been thought to cause amotivation, but the relationship between cannabis and apathy, anhedonia, and reward processing remains poorly characterised. In this systematic review, we evaluated whether cannabis exposure acutely and/or non-acutely was associated with altered reward processing using questionnaire, behavioural, or functional neuroimaging measures. Questionnaire studies demonstrated greater anhedonia in adolescent cannabis users, and some indication of greater apathy in young adult cannabis users. Behavioural studies yielded some evidence of reduced reward learning in adolescent cannabis users, though there were too few studies in this category for reliable conclusions. Finally, longitudinal and acute functional neuroimaging studies showed an association between cannabis and blunted neural responses to reward, which did not emerge consistently in cross-sectional studies. The current results suggest that cannabis use is associated with specific impairments in reward and motivation. Future large-scale, longitudinal studies which use multiple behavioural and neuroimaging measures of reward processing may further clarify the impact of cannabis use on motivational and reward processes, and neural networks.
... During pregnancy and the post-partum period, young mothers can have mixed emotions, including joy and worry, about their new responsibility and may feel alone and isolated, which exacerbates their feelings of vulnerability and low self-esteem [8]. At the same time, cognitive and neurophysiological development in adolescent mothers still has to be completed [9]. Such immaturity may influence adolescent mothers, making them less cognitively competent with regard to taking on their parental role (cognitive readiness to parent) and to knowledge about the abilities of the child in the different stages of development [10]. ...
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This study examined the psychopathological and psychosocial risk profile and the quality of mother–infant interaction in 98 adolescent and young mother–infant dyads. At their infant’s age of 3 months, mothers filled in a socio-demographic form and completed a test battery: EPDS for depression, STAY-I for anxiety, PSI-SF for parenting stress, MPSS for social support, AAI for maternal attachment and reflective functioning, CECA for adverse childhood experiences, Care-Index and Mind-mindedness coding system for mother–infant interaction. Results showed that motherhood in adolescence was associated with several psychosocial risk factors. Adolescent and young mothers have depression (25%), anxiety (29%) and insecure attachment (65%), with low reflective functioning, of whom 18% have disorganized attachment. A total of 54% of the mothers had at least one adverse childhood experience. Furthermore, adolescent mothers had low sensitivity and mind-mindedness and high intrusiveness, and their infant had low responsiveness and high passive behaviors. Mothers under 18 have experienced more sexual abuse, are more likely to be single and have been followed by child social services more than mothers aged 18–21. Adolescent mothers have a high-risk psychopathological and psychosocial profile that affects their ability to mentalize and build an adequate relationship with the child. It appears to be important to support the adolescent mother–child relationship.
... However, impact of early unilateral deprivation/ stimulation and delayed bilateral restoration on bilateral processing, and whether unilaterally driven reorganizations can be reversed in adolescence, remains unknown. Although adolescence is a later phase of life occurring after the close of early auditory sensitive periods, it is wide-spanning (10-24 years, Sawyer et al., 2018) and known as an extended period of dynamic and individually variable cortical change (Foulkes & Blakemore, 2018;Giedd, 2004;Giedd et al., 1999;Steen et al., 1997). ...
Article
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Unilateral auditory deprivation in early childhood can lead to cortical strengthening of inputs from the stimulated side, yet the impact of this on bilateral processing when inputs are later restored beyond an early sensitive period is unknown. To address this, we conducted a longitudinal study with 13 bilaterally profoundly deaf adolescents who received unilateral access to sound via a cochlear implant (CI) in their right ear in early childhood before receiving bilateral access to sound a decade later via a second CI in their left ear. Auditory-evoked cortical responses to unilateral and bilateral stimulation were measured repeatedly using electroencephalogram from 1 week to 14 months after activation of their second CI. Early cortical responses from the newly implanted ear and bilateral stimulation were atypically lateralized to the left ipsilateral auditory cortex. Duration of unilateral deafness predicted an unexpectedly stronger representation of inputs from the newly implanted, compared to the first implanted ear, in left auditory cortex. Significant initial reductions in responses were observed, yet a left-hemisphere bias and unequal weighting of inputs favoring the long-term deaf ear did not converge to a balanced state observed in the binaurally developed system. Bilateral response enhancement was significantly reduced in left auditory cortex suggesting deficits in ipsilateral response inhibition of new, dominant, inputs during bilateral processing. These findings paradoxically demonstrate the adaptive capacity of the adolescent auditory system beyond an early sensitive period for bilateral input, as well as restrictions on its potential to fully reverse cortical imbalances driven by long-term unilateral deafness.
... The adolescence phase is characterized by increased reward-seeking behavior. The brain undergoes significant neurodevelopmental changes occurring between the childhood phase and young adulthood period, which continues until the age of 25 (Pfefferbaum et al., 1994;Giedd, 2004). Human and animal studies both have suggested differential developmental trajectories of limbic reward systems relative to top-down prefrontal control systems during adolescence, with limbic systems developing earlier than prefrontal control regions. ...
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Evidence in the literature suggests that sleep deprivation during early-life developmental stages, by impacting important processes such as the reward circuit maturation, may increase the vulnerability for alcohol and substance use. The mechanisms involved are not fully understood. In this study, utilizing our previously established model, we examined the impact of early-life sleep deprivation on alcohol consumption in adolescent rats. Male Sprague Dawley rats served as either the control (CON) or sleep-deprived (SD) group. Sleep deprivation was induced using a Pinnacle automated sleep deprivation apparatus. The SD group of rats was sleep deprived for 6–8 h/day for 14 days from postnatal day (PND)19 to PND32. At PND33, anxiety- and depression-like behaviors were assessed in rats using elevated plus maze and sucrose splash test, respectively. At PND39, alcohol consumption was assessed in rats for five consecutive days using the two-bottle choice paradigm, water versus 5% ethanol. SD rats exhibited significant anxiety- and depression-like behaviors as compared to CON rats. Interestingly, SD rats consumed a larger volume of alcohol when compared to CON rats, which was significantly higher at day 5 (mean of alcohol consumption (ml) ± SD; CON = 6.67 ± 3.42; SD = 19.00 ± 6.05, p = 0.0126). SD rats also showed high preference for alcohol over water, which was significantly higher at day 5 (mean of alcohol preference (%) ± SD; CON = 26.85 ± 14.97; SD = 57.69 ± 5.61, p = 0.014). Our data suggest that early-life sleep deprivation enhanced alcohol consumption in adolescent rats.
... The precuneus has been characterized by increasing functional segregation from the frontoparietal network between 8 and 26 years of age 17 . In addition to the late maturation of frontal lobe functions characterized by the well-known back-to-front maturational pattern of the brain [2][3][4]18 , the precuneus is also a subject of significant developmental changes in adolescence. ...
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Current theories of human neural development emphasize the posterior-to-anterior pattern of brain maturation. However, this scenario leaves out significant brain areas not directly involved with sensory input and behavioral control. Suggesting the relevance of cortical activity unrelated to sensory stimulation, such as sleep, we investigated adolescent transformations in the topography of sleep spindles. Sleep spindles are known to be involved in neural plasticity and in adults have a bimodal topography: slow spindles are frontally dominant, while fast spindles have a parietal/precuneal origin. The late functional segregation of the precuneus from the frontoparietal network during adolescence suggests that spindle topography might approach the adult state relatively late in development, and it may not be a result of the posterior-to-anterior maturational pattern. We analyzed the topographical distribution of spindle parameters in HD-EEG polysomnographic sleep recordings of adolescents and found that slow spindle duration maxima traveled from central to anterior brain regions, while fast spindle density, amplitude and frequency peaks traveled from central to more posterior brain regions. These results provide evidence for the gradual posteriorization of the anatomical localization of fast sleep spindles during adolescence and indicate the existence of an anterior-to-posterior pattern of human brain maturation.
... The limbic system matures earlier than the prefrontal cortex (PFC) and could be one reason for increased reward sensitivity resulting in increased sensation-seeking in adolescence (15)(16)(17)(18). It is argued that the delayed maturation of the PFC may represent increasing, but still incomplete, frontal control over behavior during adolescence (19,20), gradually facilitating cognitive capacities for risk assessment (14,(21)(22)(23)(24). Whereas the mechanisms by which self-regulatory and affective brain networks interact remain unclear, converging evidence suggests that the insular cortex is critical for emotion regulation, cognitive control, and ultimately flexible behavior (25)(26)(27)(28)(29). Therefore, the tendency of adolescents to engage in risky behavior may also be due to their inability to engage harm avoidance circuitry including the anterior insular cortex (AIC) during decision making (30). Within this perspective, extensive review of the literature suggests that the key role of the AIC is in the integration of top-down cognitive predictions and bottom-up interoceptive signals for emotional awareness (31), contributing critically to the cognitive control network implicated in the coordination of thoughts and actions (32). ...
Article
Significance Clinical evidence suggests that adolescents engage in dangerous activities despite understanding the risks involved, questioning the theory of decreased top-down control of the immature prefrontal cortex promoting adolescent disinhibited behaviors. In the present study, we report that adolescent rats show a much higher degree of inflexible behavior when making decisions under conflict compared to adults. Unexpectedly, we identified a lower excitability of layer 5 pyramidal neurons in the anterior insular cortex (AIC) of adolescent rats and smaller synaptic glutamatergic inputs to these cells but no difference in layer 5 prefrontal cortex pyramidal neurons. Chemogenetic activation of AIC neurons reduced persistent reward-seeking despite punishment, suggesting that the delayed maturation of the insula may promote inflexible reward-related behaviors in adolescent rats.
... Hence, age-related increases in these cognitive skills may help children better determine when it is adaptive to engage proactive control across different contexts. Moreover, based on the DMC theory, proactive control is subserved by sustained activation of the lateral prefrontal cortex (Braver et al., 2009), which develops rapidly during the primary school period (Giedd, 2004). It is possible that the neurobiological maturation of the lateral prefrontal cortex promotes the consistent use of proactive control across tasks. ...
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Proactive control, the ability to maintain task-relevant information in preparation for upcoming targets, has been shown to critically depend on working memory. The present study aimed to investigate the development of proactive control and its relationship with working memory in school-age children. A total of 135 Chinese school-age children were recruited. Among them, 122 children (7-year-olds: 41; 9-year-olds: 41; 11-year-olds: 40) contributed useable data for both proactive control and working memory. The results showed that proactive control efficiency on an inhibition task improved significantly from the 7-year-olds to both the 9- and 11-year-olds, while proactive control efficiency on a switching task improved significantly from both the 7- and 9-year-olds to the 11-year-olds. Besides, proactive control indices correlated significantly between the inhibition and switching tasks for the 11-year-olds but not for the 7- or 9-year-olds, suggesting that consistency in proactive control engagement across tasks may be low at early primary school years but increases at later periods. Furthermore, working memory was positively correlated with proactive control efficiency for the 7-year-olds but not for the 9- or 11-year-olds, suggesting that the relationship between proactive control and working memory may decrease with age. These results were replicated in an independent sample. Altogether, the present study advances our understanding of the development of proactive control as well as its relationship with working memory in school-age children.
... Females typically mature earlier than males, where females start the adolescent period around 10-11 years, and males at around 11.5 years old (Malina and Bouchard, 1992). The difference in timing of maturation is also visible in brain maturation, more specifically, in the increase in frontal gray matter that reaches its peak at different ages for both sexes (11.0 years for females and 12.1 years for males) (Giedd, 2004). ...
Article
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The development of executive functions (EF) has been widely investigated and is associated with various domains of expertise, such as academic achievement and sports performance. Multiple factors are assumed to influence the development of EF, among them biological maturation. Currently the effect of biological maturation on EF performance is largely unexplored, in contrast to other domains like physical development or sports performance. Therefore, this study aimed (a) to explore the effect of chronological age on EF performance and (b) to investigate to what extent age-related changes found in EF are affected by biological maturation on both sexes. To this end, EF performance and degree of maturity, indexed by percentage of predicted adult height (%PAH), of 90 adolescents (11–16 years old, 54% males) were measured on three occasions in a time frame of 12 months. A Generalized Estimating Equation (GEE) approach was used to examine the association between chronological age and %PAH and the weighted sum scores for each EF component (i.e., inhibition, planning, working memory, shifting). All models were run separately for both sexes. The males’ results indicated that EF performance improved with age and degree of maturity on all four components. Interaction effects between age and %PAH on inhibition showed that at a younger age, males with a higher %PAH had a lower chance of performing well on inhibition, whereas at later ages, males with a higher %PAH had a higher chance to have a good inhibition performance. For working memory, it seems that there is no maturity effect at a younger age, while at later ages, a disadvantage for later maturing peers compared to on-time and earlier maturing male adolescents emerged. Females showed slightly different results. Here, age positively influenced EF performance, whereas maturity only influenced inhibition. Interaction effects emerged for working memory only, with opposite results from the males. At younger ages, females with lower %PAH values seem to be scoring higher, whereas at later ages, no maturity effect is observed. This study is one of the first to investigate the effect of biological maturation on EF performance, and shows that distinct components of EF are influenced by maturational status, although the effects are different in both sexes. Further research is warranted to unravel the implications for maturation-driven effects on EF that might significantly affect domains of human functioning like academic achievement and social development.
... Sur le plan neurobiologique, durant l'adolescence et le début de l'âge adulte, le cerveau connaît un remodelage intense : la myélinisation des axones qui renforce la communication cérébrale entraîne une augmentation du volume de la substance blanche et à l'inverse, l'élimination des connexions inutiles, ou peu actives, entre neurones (élagage synaptique, ou « pruning ») se traduit par une diminution du volume de la substance grise (Giedd 2004). Cette période est souvent qualifiée de « fenêtre de vulnérabilité » pendant laquelle le cerveau va être particulièrement sensible à la toxicité de l'alcool (Spear 2018). ...
Thesis
Le comportement de binge drinking (BD), défini comme la répétition d'épisodes de consommation rapide et massive d'alcool (éthanol), est très répandu chez les adolescents et jeunes adultes et peut conduire à des déficits de mémoire à long terme. Cependant, les mécanismes neurobiologiques de l'éthanol lors des premiers épisodes de BD, qui pourraient révéler les éléments de base de la réponse à l'alcool, restent méconnus. Dans un premier travail, notre laboratoire avait mis en évidence que deux épisodes de BD chez le rat adolescent (EtOH 3g/kg i.p.; éthanolémie 2g/L) suffisaient à induire des déficits d'apprentissage après 48h, associés sur le plan cellulaire à une abolition de la dépression à long terme et à une augmentation de la potentialisation à long terme – deux types de plasticité qui correspondent aux mécanismes cellulaires de la mémoire – enregistrées ex vivo dans l'aire CA1 de l'hippocampe, et à une augmentation de la fonctionnalité des sous-unités GluN2B du récepteur au glutamate de type NMDA. Tout l'enjeu de ce travail de thèse a été de déterminer comment ces effets apparaissaient, en envisageant l'implication de mécanismes épigénétiques et/ou neuroinflammatoires. En combinant des approches comportementales, électrophysiologiques sur tranches d'hippocampe, pharmacologiques et biochimiques, nous démontrons que 48h après l'éthanol, l'expression de l'histone déacétylase de type 2 (HDAC2) est augmentée dans l'aire CA1 et que l'administration préalable de butyrate de sodium (un inhibiteur des HDAC) prévient l'ensemble des effets de l'éthanol. De plus, nos résultats indiquent une sous-expression neuronale du récepteur TLR4 dans CA1 48h après les deux épisodes de BD et l'administration de substances anti-inflammatoires telles que la minocycline, l'indométhacine ou l'antagoniste du TLR4, le TAK-242, préviennent également les perturbations induites par l'éthanol. Nous concluons ainsi que dès les premières expositions, le BD déclenche des processus neuroinflammatoires qui semblent intervenir précocement, mais également des processus épigénétiques qui interviennent peut-être plus tardivement et qui perturbent la plasticité synaptique dans l'hippocampe et par conséquent, l'apprentissage. Bloquer la mise en place de tels processus ouvre des perspectives intéressantes dans la prévention des déficits mnésiques chez les binge drinkers
Article
We examined bidirectional, temporal associations between daily sleep and affect under naturally restricted (school) and unrestricted (vacation) sleep opportunities, while incorporating valence (positive/negative) and arousal (high/low) dimensions of affect. Sleep and affect were measured over 2 weeks of school and 2 weeks of vacation in 205 adolescents (54.1% females, Mage = 16.9 years), providing 5,231 days of data. Total sleep time and sleep efficiency were measured using actigraphy and sleep diary. High‐ and low‐arousal positive and negative affect were self‐reported each afternoon. Between‐ and within‐person sleep–affect associations were tested using cross‐lagged, multilevel models. Lagged outcome, day of the week, study day and socio‐demographics were controlled. Bidirectional associations between self‐report sleep and affect were found between‐persons: longer self‐report total sleep time associated with lower high‐ and low‐arousal negative affect. Higher high‐arousal positive affect associated with longer actigraphy total sleep time between‐persons, but predicted shorter same‐night actigraphy total sleep time within‐persons. Results did not differ between school and vacation. Significant within‐person random effects demonstrate individual differences in daily sleep–affect associations. Associations differed based on sleep measurement and affect dimensions, highlighting the complex sleep–affect relationship. Strong between‐person associations between self‐report sleep and affect suggest improving either sleep or mood may benefit the other; alternatively, addressing a common cause may lead to changes in both sleep and affect. Although overall high‐arousal positive affect was protective of sleep duration, on a day‐to‐day basis, higher‐than‐usual high‐arousal positive affect may reduce sleep duration on nights it is experienced. Further research needs to identify causes of individual differences in sleep–affect associations.
Article
Adolescence, the period from 11 to 21 years of age, bridges the chasm between childhood and adulthood. Adolescence can be challenging as bodies, cognition, and personality go through major transformations, but it is also a time of great joy as confident adults with a clear identity develop. Dentists need to be knowledgeable about the developmental characteristics of this group because some of the cognitive and emotional changes make adolescents vulnerable to new fears. Dentists must tailor behavior guidance to this developing psyche in a way that respects independence and promotes confidence to foster lifelong positive views of dentistry.
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Alcohol is one of the most widely used recreational substances worldwide, with drinking frequently initiated during adolescence. The developmental state of the adolescent brain makes it vulnerable to initiating alcohol use, often in high doses, and particularly susceptible to alcohol-induced brain changes. Microglia, the brain parenchymal macrophages, have been implicated in mediating some of these effects, though the role that these cells play in the progression from alcohol drinking to dependence remains unclear. Microglia are uniquely positioned to sense and respond to central nervous system insult, and are now understood to exhibit innate immune memory, or “priming,” altering their future functional responses based on prior exposures. In alcohol use disorders (AUDs), the role of microglia is debated. Whereas microglial activation can be pathogenic, contributing to neuroinflammation, tissue damage, and behavioral changes, or protective, it can also engage protective functions, providing support and mediating the resolution of damage. Understanding the role of microglia in adolescent AUDs is complicated by the fact that microglia are thought to be involved in developmental processes such as synaptic refinement and myelination, which underlie the functional maturation of multiple brain systems in adolescence. Thus, the role microglia play in the impact of alcohol use in adolescence is likely multifaceted. Long-term sequelae may be due to a failure to recover from EtOH-induced tissue damage, altered neurodevelopmental trajectories, and/or persistent changes to microglial responsivity and function. Here, we review critically the literature surrounding the effects of alcohol on microglia in models of adolescent alcohol misuse. We attempt to disentangle what is known about microglia from other neuroimmune effectors, to which we apply recent discoveries on the role of microglia in development and plasticity. Considered altogether, these studies challenge assumptions that proinflammatory microglia drive addiction. Alcohol priming microglia and there by perturbing their homeostatic roles in neurodevelopment, especially during critical periods of plasticity such as adolescence, may have more serious implications for the neuropathogenesis of AUDs in adolescents.
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Cognitive theories of depression contend that biased cognitive information processing plays a causal role in the development of depression. Extensive research shows that deeper processing of negative and/or shallower processing of positive self-descriptors (i.e., negative and positive self-schemas ) predicts current and future depression in adults and children. However, the neural correlates of the development of self-referent encoding are poorly understood. We examined children's self-referential processing using the self-referent encoding task (SRET) collected from 74 children at ages 6, 9, and 12; around age 10, these children also contributed structural magnetic resonance imaging data. From age 6 to age 12, both positive and negative self-referential processing showed mean-level growth, with positive self-schemas increasing relatively faster than negative ones. Further, voxel-based morphometry showed that slower growth in positive self-schemas was associated with lower regional gray matter volume (GMV) in ventrolateral prefrontal cortex (vlPFC). Our results suggest that smaller regional GMV within vlPFC, a critical region for regulatory control in affective processing and emotion development, may have implications for the development of depressogenic self-referential processing in mid-to-late childhood.
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Nicotine addiction develops predominantly during human adolescence through smoking. Self-administration experiments in rodents verify this biological preponderance to adolescence, suggesting evolutionary-conserved and age-defined mechanisms which influence the susceptibility to nicotine addiction. The hippocampus, a brain region linked to drug-related memory storage, undergoes major morpho-functional restructuring during adolescence and is strongly affected by nicotine stimulation. However, the signaling mechanisms shaping the effects of nicotine in young vs. adult brains remain unclear. MicroRNAs (miRNAs) emerged recently as modulators of brain neuroplasticity, learning and memory, and addiction. Nevertheless, the age-dependent interplay between miRNAs regulation and hippocampal nicotinergic signaling remains poorly explored. We here combined biophysical and pharmacological methods to examine the impact of miRNA-132/212 gene-deletion (miRNA-132/212−/−) and nicotine stimulation on synaptic functions in adolescent and mature adult mice at two hippocampal synaptic circuits: the medial perforant pathway (MPP) to dentate yrus (DG) synapses (MPP-DG) and CA3 Schaffer collaterals to CA1 synapses (CA3–CA1). Basal synaptic transmission and short-term (paired-pulse-induced) synaptic plasticity was unaltered in adolescent and adult miRNA-132/212−/− mice hippocampi, compared with wild-type controls. However, nicotine stimulation promoted CA3–CA1 synaptic potentiation in mature adult (not adolescent) wild-type and suppressed MPP-DG synaptic potentiation in miRNA-132/212−/− mice. Altered levels of CREB, Phospho-CREB, and acetylcholinesterase (AChE) expression were further detected in adult miRNA-132/212−/− mice hippocampi. These observations propose miRNAs as age-sensitive bimodal regulators of hippocampal nicotinergic signaling and, given the relevance of the hippocampus for drug-related memory storage, encourage further research on the influence of miRNAs 132 and 212 in nicotine addiction in the young and the adult brain.
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Although negative early life experiences are associated with an increased risk of developing psychopathology, some individuals exposed to childhood adversity demonstrate psychological resilience. Little is known about the neural correlates of resilience, especially in young people. To address this gap, we conducted a systematic review of neuroimaging studies of resilience in youth. The PubMed, Web of Science, Scopus, and PsycINFO databases were searched; 5,482 studies were identified. Following title/abstract screening, and full reading of the remaining articles, 22 studies based on 19 unique datasets were included. We found preliminary evidence that resilience is associated with structural, functional, and connectivity differences in young people, as assessed using structural and functional MRI and diffusion tensor imaging methods. Despite heterogeneity in definitions/assessment of resilience and a limited number of studies, the neuroimaging literature suggests some convergence across modalities regarding brain regions linked to resilience (especially the prefrontal cortex). Future studies would benefit from adopting longitudinal designs, broader conceptualisations of resilience that capture the impact of adversity exposure, and a dimensional approach to psychopathology.
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Socialization happens so regularly in humans that it can be perceived as an effortless activity. However, it reflects a sophisticated behavior, pervaded by anticipation and emotion. The fast-paced social interplay, strongly mediated by facial expressions, can be considered one of the most frequent high-order motor acts within the human behavioral repertoire. The ability to adequately process social feedback is critical for appropriate socialization and affects well-being. The social difficulties often observed in psychiatric patients highlight the link between mental health and successful socialization and the importance of characterizing the behavioral and neural mechanisms of social interaction. This chapter will present some cross-species evidence on the cortical regions engaged during social interactions including facial expressions, and the impact of induced or perceived social stress on the experience of social interactions.
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The Synaptotagmin-1 encoding gene ( SYT1 ) is a key regulator of neurotransmitter release and is associated with cognitive and psychiatric phenotypes in GWAS, and with ADHD in single-gene studies, raising the need for dissecting possible cross-trait effects on clinical and brain phenotypes. Inferences about white matter microstructure can be made by diffusion-tensor imaging (DTI), which makes this method a promising tool in the understanding of biological changes that underpin cognitive functions and brain disorders. Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder that affects multiple functioning domains, highly overlapping with other psychiatric disorders, and known to involve white matter abnormalities and neurotransmission dysfunction. Using a set-based analysis, the present study investigates how genetic variants within SYT1 might affect brain white matter at a cellular level using DTI in adults with ADHD (n = 85). The combined effect of all measured variations in the gene (i.e., 468 variants) was evaluated concerning specific white matter tracts. Set-based analysis was performed in PLINK software and followed by in silico analysis of all variants included in the study. SYT1 gene was nominally associated with white matter changes in two important tracts: forceps major and inferior fronto-occipital fasciculus. In addition, two regions within the SYT1 have more consistent associations with different white matter tracts. These findings endorse the involvement of SYT1 on psychiatric phenotypes and suggest that white matter tracts underlie this complex relationship.
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The adolescent brain undergoes tremendous structural and functional changes throughout puberty. Previous research has demonstrated that pubertal hormones can modulate sexually dimorphic changes in cortical development, as well as age‐related maturation of the neural activity underlying cognitive processes. However, the precise impact of pubertal hormones on these functional changes in the developing human brain remains poorly understood. In the current study, we quantified the neural oscillatory activity serving visuospatial processing using magnetoencephalography, and utilized measures of dehydroepiandrosterone (DHEA) as an index of development during the transition from childhood to adolescence (i.e., puberty). Within a sample of typically developing youth (ages 9–15), a novel association between pubertal DHEA and theta oscillatory activity indicated that less mature children exhibited stronger neural responses in higher‐order prefrontal cortices during the visuospatial task. Theta coherence between bilateral prefrontal regions also increased with increasing DHEA, such that network‐level theta activity became more distributed with more maturity. Additionally, significant DHEA‐by‐sex interactions in the gamma range were centered on cortical regions relevant for attention processing. These findings suggest that pubertal DHEA may modulate the development of neural oscillatory activity serving visuospatial processing and attention functions during the pubertal period.
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Adolescent pregnancy (AP) is a significant public health issue. Child maltreatment (CM) represents an established risk factor, yet little is known about the explanatory mechanisms linking the phenomena. Informed by developmental theory, this study prospectively tested seven multi-level, indirect pathways that could plausibly explain the relationship between CM and AP: (1) substance use (polysubstance use and frequency); (2) sexual risk behavior; (3) depressive symptoms; (4) posttraumatic stress disorder symptoms; (5) cognitive dysregulation; (6) pregnancy desire and difficulty expectancies; and (7) age at menarche. Data came from a prospective, longitudinal cohort study of 469 ethnically diverse, nulliparous adolescent females, designed to examine the impact of substantiated CM on reproductive outcomes such as pregnancy and childbirth (265 maltreated and 204 demographically matched comparison adolescents). A multiple-mediator structural equation model was conducted to simultaneously test multiple indirect effects while accounting for confounding variables. Maltreatment had an indirect effect on pregnancy via substance use and higher pregnancy desire/lower perceived difficulty. Findings represent a step towards elucidating pathways linking CM with AP. Recommendations are offered to prevent pregnancy by addressing the pregnancy-specific mechanisms that are part of the maltreatment sequelae.
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The numerous multistable phenomena in vision, hearing and touch attest that the inner workings of perception are prone to instability. We investigated a visual example—binocular rivalry—with an accurate no-report paradigm, and uncovered developmental and maturational lifespan trajectories that were specific for age and sex. To interpret these trajectories, we hypothesized that conflicting objectives of visual perception—such as stability of appearance, sensitivity to visual detail, and exploration of fundamental alternatives—change in relative importance over the lifespan. Computational modelling of our empirical results allowed us to estimate this putative development of stability, sensitivity, and exploration over the lifespan. Our results confirmed prior findings of developmental psychology and appear to quantify important aspects of neurocognitive phenotype. Additionally, we report atypical function of binocular rivalry in autism spectrum disorder and borderline personality disorder. Our computational approach offers new ways of quantifying neurocognitive phenotypes both in development and in dysfunction.
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We sought to elucidate the acute effects of high-intensity interval training (HIIT) among college students with and without attention-deficit/hyperactivity disorder (ADHD). Participants were age- and sex-matched across ADHD (n = 18) and non-ADHD groups (n = 18) and both groups completed baseline (non-HIIT) and experimental sessions (HIIT). We examined within- and between-subject effects on a continuous performance task (CPT) and self-reported ADHD and internalizing symptomatology. We found that the degree of improvement on ADHD and depressive symptomatology, as well as processing speed and response variability following HIIT was significantly greater for the ADHD group than the comparison group. Further investigations such as randomized controlled trials focusing on the chronic effects of sustained HIIT interventions are needed to substantiate the potential feasibility and efficacy of HIIT as an intervention. HIIT may be a useful adjunct to psychosocial and/or pharmacological treatments for college students with ADHD because it: (a) yields immediate, acute improvements in executive functioning, ADHD, and mood; (b) promotes improved physical and mental health; (c) poses a relatively low risk of deleterious effects in apparently healthy college students. Even with the need for additional research, current data suggest a single, brief, high-intensity bout of aerobic exercise can yield immediate significant short-term improvements. These improvements may enhance functioning and improve outcomes for college students with ADHD.
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The mismatch between teenagers’ late sleep phase and early school start times results in acute and chronic sleep reductions. This is not only harmful for learning but may reduce career prospects and widen social inequalities. Delaying school start times has been shown to improve sleep at least short-term but whether this translates to better achievement is unresolved. Here, we studied whether 0.5–1.5 years of exposure to a flexible school start system, with the daily choice of an 8 AM or 8:50 AM-start, allowed secondary school students (n = 63–157, 14–21 years) to improve their quarterly school grades in a 4-year longitudinal pre-post design. We investigated whether sleep, changes in sleep or frequency of later starts predicted grade improvements. Mixed model regressions with 5111–16,724 official grades as outcomes did not indicate grade improvements in the flexible system per se or with observed sleep variables nor their changes—the covariates academic quarter, discipline and grade level had a greater effect in our sample. Importantly, our finding that intermittent sleep benefits did not translate into detectable grade changes does not preclude improvements in learning and cognition in our sample. However, it highlights that grades are likely suboptimal to evaluate timetabling interventions despite their importance for future success.
Chapter
An understanding of executive functioning begins with knowing the underlying neural substrates and integrated circuitry involved in higher‐order cognitive processing. Working memory and attention are acknowledged as fundamental aspects of executive functioning, and evaluating working memory and attention is seen as a critical component of assessing executive functions. Regardless of which direct and indirect measures are chosen, the neuropsychological assessment of children in general, and executive functioning specifically, is extremely complex. The Delis‐Kaplan Executive Function System (D‐KEFS) was one of the first instruments specifically designed to evaluate executive functioning. Trail‐making tests have been a popular procedure with both children and adults and have been incorporated into many neuropsychological batteries such as the D‐KEFS. Despite the challenges inherent to the accurate assessment of executive functions in children and adolescents, it is crucial to provide the foundation for effective intervention strategies.
Thesis
Les adolescents vivant avec le VIH (AVVIH) doivent faire face aux défis de la prise en charge (PEC) globale du VIH incluant l'annonce du statut, l'accès et l'observance au traitement antirétroviral, et leur santé sexuelle et reproductive (SSR). L'objectif global de cette thèse visait à améliorer les connaissances sur le rôle déterminant de l'annonce du statut d'infection par le VIH dans la prise en charge et le devenir des adolescents vivant avec le VIH en Afrique de l'Ouest pour améliorer leur prise en charge globale, incluant les questions de SSR. Nous avons étudié l'annonce du diagnoistic, ses facteurs associés et ses conséquences sur le devenir des AVVIH dans une cohorte pilote multicentrique en Côte d'Ivoire et au Togo. Nous rapportons également le vécu qualitatif de l'annonce du diagnostic VIH, chez les AVVIH. Nous avons analysé l'association entre annonce du diagnostic VIH, santé mentale et succès virologique. Ensuite nous avons analysé l'offre de services en SSR dédiée aux AVVIH dans les services pédiatriques de PEC du VIH. Enfin, nous avons synthétisé les données disponibles sur l'efficacité des interventions en SSR ciblant les AVVIH en Afrique Sub-Saharienne. Nos travaux montrent que malgré les progrès réalisés, l'annonce reste trop tardive, souvent réalisée à un stade avancé de la maladie. Nos travaux suggèrent l'importance d'associer aussi bien les professionnels de santé que les parents et les pairs dans ce processus d'annonce. Nos travaux soulignent le rôle déterminant de l'annonce dans de bonnes conditions pour améliorer la santé mentale des AVVIH, leur prise en charge et leur devenir. Enfin, les programmes pédiatriques de PEC du VIH à Abidjan intégraient peu de services de SSR et les interventions de soutien psychologique et des thérapies cognitives comportementales répétées, impliquant les professionnels et las pairs améliorent la SSR des AVVIH et pouraient être mises en Œuvre en Afrique de l'Ouest.
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Individuals exhibit variability in the degree of correspondence between autonomic and subjective indicators of emotional experience. The current study examined whether convergence between autonomic arousal and negative emotions during emotion-inducing story vignettes is associated with internalizing symptoms in school-aged children. A diverse sample of 97 children aged 8 to 12 years participated in this study in which they reported on their anxiety and depression. Children’s electrodermal activity was assessed while they read vignettes depicting children experiencing sadness and fear. Participants also reported on their emotional reaction to the vignettes. Children’s anxiety and electrodermal activity to fear vignettes were associated only at high levels, but not mean or low levels, of self-reported negative emotions to fear vignettes. These findings suggest that hyperawareness, in which self-reported negative emotionality is high when physiological reactivity is also high, is associated with greater risk for anxiety, but not depression, during middle childhood.
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We present here results from analysis of the formation of brain bioelectrical activity in children and adolescents living in the northern region of Russia based on evaluation of integral multichannel EEG parameters. A total of 33 boys and 32 girls aged 7–18 years studying at rural schools took part in the study. The study was run in two stages, each of which consisted of autumn and spring sessions. EEG recordings were made and used to build the structure function and compute the generalized spectrum, along with integral parameters characterizing the temporal (0 ≤ Pt ≤ 1) and spatial (0 ≤ Ps ≤ 1) connectivity of EEG processes. The limiting values of these parameters (0, 1) correspond to the cases of the spatial or temporal organization of the EEG being either completely ordered or completely random. Decreases in Ps were found with increasing age, evidencing increases in spatial connectivity of EEG processes in students from younger to older grades. Conversely, Pt increased with age, characterizing a decrease in the time scale of connectivity and the inertia of EEG processes, and could reflect an increase in the level of functional mobility (lability) of the CNS with increasing age. Assessments of the age-related dynamics of integral EEG parameters in northern schoolchildren were found to depend on season (autumn–spring) and the contingent of subjects selected.
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Recent findings indicate that stress exposure during adolescence contributes to the development of both nicotine use and affective disorders, suggesting a potential shared biological pathway. One key system that may mediate the association between adolescent stress and nicotine or affective outcomes is the hypothalamic-pituitary-adrenal (HPA) axis. Here we reviewed evidence regarding the effects of adolescent stress on nicotine responses and affective phenotypes, and the role of the HPA-axis in these relationships. Literature indicates that stress, possibly via HPA-axis dysfunction, is a risk factor for both nicotine use and affective disorders. In rodent models, adolescent stress modulates behavioral responses to nicotine and increases the likelihood of affective disorders. The exact role that the HPA-axis plays in altering nicotine sensitivity and affective disorder development after adolescent stress remains unclear. However, it appears likely that adolescent stress-induced nicotine use and affective disorders are precipitated by repetitive activation of a hyperactive HPA-axis. Together, these preclinical studies indicate that adolescent stress is a risk factor for nicotine use and anxiety/depression phenotypes. The findings summarized here suggest that the HPA-axis mediates this relationship. Future studies that pharmacologically manipulate the HPA-axis during and after adolescent stress are critical to elucidate the exact role that the HPA-axis plays in the development of nicotine use and affective disorders following adolescent stress.
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Although behavioral evidence provides support for the notion that attention deficit-hyperactivity disorder (ADHD) is related to central nervous system dysfunction, there is little direct evidence to reveal which neurometabolic systems or brain structures are involved. Recent magnetic resonance imaging (MRI) studies suggest that, compared to nondisabled controls, ADHD children may have a smaller right frontal region. Morphometric analysis of MRI scans was used in this exploratory study to determine whether correlated regional variation might exist in the corpus callosum of children with ADHD. While all MRI scans were judged to be clinically normal, morphometric analysis revealed that, compared to nondisabled controls, ADHD children had a smaller corpus callosum, particularly in the region of the genu and splenium, and in the area just anterior to the splenium. Interhemispheric fibers in these regions interconnect the left and right frontal, occipital, parietal, and posterior temporal regions. These results suggest that subtle differences may exist in the brains of children with ADHD and that deviations in normal corticogenesis may underlie the behavioral manifestations of this disorder.
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Gonadal steroids are known to influence hippocampal physiology in adulthood. It is presently unknown whether gonadal steroids influence the morphology of hippocampal neurons in the adult intact rat brain. In order to determine whether female sex hormones influence hippocampal morphology in the intact adult, we performed Golgi impregnation on brains from ovariectomized rats and ovariectomized rats which received estradiol or estradiol and progesterone replacement. Removal of circulating gonadal steroids by ovariectomy of adult female rats resulted in a profound decrease in dendritic spine density in CA1 pyramidal cells of the hippocampus. Estradiol replacement prevented the observed decrease in dendritic spine density; progesterone augmented the effect of estradiol within a short time period (5 hr). Ovariectomy or gonadal steroid replacement did not affect spine density of CA3 pyramidal cells or granule cells of the dentate gyrus. These results demonstrate that gonadal steroids are necessary for the maintenance of normal adult CA1 hippocampal pyramidal cell structure. The short time course required to observe these effects (3 d for the estradiol effect and 5 hr for the progesterone effect) implies that CA1 pyramidal cell dendritic spine density may fluctuate during the normal (4-5 d) rat estrous cycle.
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To model in vivo the dynamic interrelations of head size, gray matter, white matter, and cerebrospinal fluid (CSF) volumes from infancy to old age using magnetic resonance imaging (MRI). Cross-sectional, between-subjects using an age-regression model. A Veterans Affairs medical center and community hospitals. There were 88 male and female subjects aged 3 months to 30 years whose clinical MRI film had been read as normal and 73 healthy male volunteers aged 21 to 70 years who had an MRI performed specifically for this study. These MRI data were quantified using a semiautomated computer technique for segmenting images into gray matter, white matter, and CSF compartments. The cortex was defined geometrically as the outer 45% on each analyzed slice, and the volumes of cortical white matter, gray matter, and CSF were computed. Subcortical (ventricular) CSF volume was computed for the inner 55% of each analyzed slice. In the younger sample, intracranial volume increased by about 300 mL from 3 months to 10 years. The same patterns of change in volume of each compartment across the age range were seen in both sexes: cortical gray matter volume peaked around age 4 years and decreased thereafter; cortical white matter volume increased steadily until about age 20 years; cortical and ventricular CSF volumes remained constant. In the older sample, brain volumes were statistically adjusted for normal variation in head size through a regression procedure and revealed the following pattern: cortical gray matter volume decreased curvilin-early, showing an average volume loss of 0.7 mL/y, while cortical white matter volume remained constant during the five decades; complementary to the cortical gray matter decrease, cortical CSF volume increased by 0.6 mL/y and ventricular volumes increased by 0.3 mL/y. These patterns of growth and change seen in vivo with MRI are largely consistent with neuropathological studies, as well as animal models of development, and may reflect neuronal progressive and regressive processes, including cell growth, myelination, cell death, and atrophy.
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A previous study demonstrated that myelination of the superior medullary lamina along the surface of the parahippocampal gyrus is occurring in human brain during adolescence. To further investigate whether postnatal increases of myelination may continue during the second decade and possibly even longer, the extent of myelination in this region has been analyzed in 164 psychiatrically normal individuals aged newborn to 76 years. Cross sections of the hippocampal formation with adjoining hippocampal gyrus were analyzed on a blinded basis using either a global rating scale or measurements of the area of myelin staining. A curvilinear increase in the extent of myelination between the first and sixth decades of life (r = .71 and r = .67, respectively) was observed. When the area of myelination was expressed relative to brain weight, there was a twofold increase between the first and second decades and an additional increase of 60% between the fourth and sixth decades. Female subjects showed a significantly greater degree of myelin staining than did male subjects during the interval of ages 6 to 29 years; however, after the third decade, there were no gender differences in the area of myelin staining. The increased staining of myelin during the first and second decades principally occurred in the subicular region and adjacent portions of the presubiculum. During the fourth through sixth decades, however, it extended to progressively more lateral locations along the surface of the presubiculum. The precise origin(s) of the axons showing progressive myelination is unknown; however, the axons in the subiculum may include some perforant path fibers, while those found in the presubiculum may include cingulum bundle projections. Overall, our data are consistent with the idea that both early and late postnatal increases of myelination occur in a key corticolimbic relay area of the human brain and underscore the importance of applying a neurodevelopmental perspective to the study of psychopathology during childhood, adolescence, and even adulthood.
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Brain magnetic resonance images (MRI) of 104 healthy children and adolescents, age 4-18, showed significant effects of age and gender on brain morphometry. Males had larger cerebral (9%) and cerebellar (8%) volumes (P < 0.0001 and P = 0.008, respectively), which remained significant even after correction for height and weight. After adjusting for cerebral size, the putamen and globus pallidus remained larger in males, while relative caudate size was larger in females. Neither cerebral nor cerebellar volume changed significantly across this age range. Lateral ventricular volume increased significantly in males (trend for females), with males showing an increase in slope after age 11. In males only, caudate and putamen decrease with age (P = 0.007 and 0.05, respectively). The left lateral ventricles and putamen were significantly greater than the right (P = 0.01 and 0.001, respectively). In contrast, the cerebral hemispheres and caudate showed a highly consistent right-greater-than-left asymmetry (P < 0.0001 for both). All volumes demonstrated a high degree of variability. These findings highlight gender-specific maturational changes of the developing brain and the need for large gender-matched samples in pediatric neuropsychiatric studies.
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To determine whether a quantitative MR imaging method to map spin-lattice relaxation time (T1) can be used to characterize maturational changes in the normal human brain. An inversion-recovery technique was used to map T1 transversely at the level of the basal ganglia in a study population of 19 healthy children (4 to 10 years old) and 31 healthy adolescents (10 to 20 years old), and in a normative population of 20 healthy adults (20 to 30 years old). Nonparametric analysis of variance showed that T1 decreases with age in the genu, frontal white matter, caudate, putamen, anterior thalamus, pulvinar nucleus, optic radiation, cortical gray matter (all P < .0001), and occipital white matter. There was a significant reduction in T1 between childhood (mean age, 7.1 +/- 1.4) and adolescence (mean age, 13.5 +/- 2.6) in all brain structures, but there was also a significant reduction in T1 between adolescence (mean age, 13.5 +/- 2.6) and adulthood (mean age, 26.5 +/- 3.4) in all brain structures except occipital white matter. Regression shows that T1 declines to within the range (mean +/- 2 SD) of young adult T1 values by about 2 years in the occipital white matter, by about 4 years in the genu, by 11 years in the cortical gray matter, by 11 years in the frontal white matter, and by 13 years in the thalamus. Brain structures mature at strikingly different rates, yet the ratio of gray matter T1 to white matter T1 does not change significantly with age. Thus, conventional MR imaging methods based on inherent contrast are insensitive to these changes. Age-related changes tend to reach completion sooner in white matter than in gray matter tracts. Such normative data are essential for studies of specific pediatric disorders and may be useful for assessing brain maturation in cases of developmental delay.
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Structural maturation of fiber tracts in the human brain, including an increase in the diameter and myelination of axons, may play a role in cognitive development during childhood and adolescence. A computational analysis of structural magnetic resonance images obtained in 111 children and adolescents revealed age-related increases in white matter density in fiber tracts constituting putative corticospinal and frontotemporal pathways. The maturation of the corticospinal tract was bilateral, whereas that of the frontotemporal pathway was found predominantly in the left (speech-dominant) hemisphere. These findings provide evidence for a gradual maturation, during late childhood and adolescence, of fiber pathways presumably supporting motor and speech functions.
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Pediatric neuroimaging studies1, 2, 3, 4, 5, up to now exclusively cross sectional, identify linear decreases in cortical gray matter and increases in white matter across ages 4 to 20. In this large-scale longitudinal pediatric neuroimaging study, we confirmed linear increases in white matter, but demonstrated nonlinear changes in cortical gray matter, with a preadolescent increase followed by a postadolescent decrease. These changes in cortical gray matter were regionally specific, with developmental curves for the frontal and parietal lobe peaking at about age 12 and for the temporal lobe at about age 16, whereas cortical gray matter continued to increase in the occipital lobe through age 20.
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The dynamic nature of growth and degenerative disease processes requires the design of sensitive strategies to detect, track and quantify structural change in the brain in its full spatial and temporal complexity. Although volumes of brain substructures are known to change during development, detailed maps of these dynamic growth processes have been unavailable. Here we report the creation of spatially complex, four-dimensional quantitative maps of growth patterns in the developing human brain, detected using a tensor mapping strategy with greater spatial detail and sensitivity than previously obtainable. By repeatedly scanning children (aged 3-15 years) across time spans of up to four years, a rostro-caudal wave of growth was detected at the corpus callosum, a fibre system that relays information between brain hemispheres. Peak growth rates, in fibres innervating association and language cortices, were attenuated after puberty, and contrasted sharply with a severe, spatially localized loss of subcortical grey matter. Conversely, at ages 3-6 years, the fastest growth rates occurred in frontal networks that regulate the planning of new actions. Local rates, profiles, and principal directions of growth were visualized in each individual child.
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Modern brain imaging techniques have now made it possible to study the neural sites and mechanisms underlying crossmodal processing in the human brain. This paper reviews positron emission tomography, functional magnetic resonance imaging (fMRI), event-related potential and magnetoencephalographic studies of crossmodal matching, the crossmodal integration of content and spatial information, and crossmodal learning. These investigations are beginning to produce some consistent findings regarding the neuronal networks involved in these distinct crossmodal operations. Increasingly, specific roles are being defined for the superior temporal sulcus, the inferior parietal sulcus, regions of frontal cortex, the insula cortex and claustrum. The precise network of brain areas implicated in any one study, however, seems to be heavily dependent on the experimental paradigms used, the nature of the information being combined and the particular combination of modalities under investigation. The different analytic strategies adopted by different groups may also be a significant factor contributing to the variability in findings. In this paper, we demonstrate the impact of computing intersections, conjunctions and interaction effects on the identification of audiovisual integration sites using existing fMRI data from our own laboratory. This exercise highlights the potential value of using statistical interaction effects to model electrophysiological responses to crossmodal stimuli in order to identify possible sites of multisensory integration in the human brain.
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Previous in vivo morphometric studies of human brain maturation between childhood and young adulthood have revealed a spatial and temporal pattern of progressive brain changes that is consistent with the post mortem cytoarchitectonic and cognitive developmental literatures. In this study, we mapped age differences in structural asymmetries at the cortical surface in groups of normally developing children (7-11 years), adolescents (12-16 years) and young adults (23-30 years) using novel surface-based mesh modeling image analytic methods. We also assessed relationships between cortical surface sulcal asymmetry and the local density of the underlying cortical gray matter. Results from this study reveal that perisylvian sulcal asymmetries are much more prominent in the adults than in the children studied. The superior posterior extent of the Sylvian fissure in the right hemisphere is approximately 7 mm more superior in the average adult than in the average child studied, whereas little difference is observed during this age range in the location of this anatomical structure in the left hemisphere. Age-related differences in Sylvian fissure asymmetry were significant (P = 0.0129, permutation test), showing increased asymmetry with increasing age. We also show age-related increases in local gray matter proportion bilaterally in the temporo-parietal cortices that are anatomically and temporally related to the sulcal asymmetries. Results from this cross-sectional study imply that asymmetries in the Sylvian fissure are dynamically changing into young adulthood and show that variability in brain tissue density is related to asymmetry in this region. These morphological differences may be related to changing cognitive abilities and are relevant in interpreting results from studies of abnormal brain development where perisylvian brain regions are implicated.
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We report the dynamic anatomical sequence of human cortical gray matter development between the age of 4-21 years using quantitative four-dimensional maps and time-lapse sequences. Thirteen healthy children for whom anatomic brain MRI scans were obtained every 2 years, for 8-10 years, were studied. By using models of the cortical surface and sulcal landmarks and a statistical model for gray matter density, human cortical development could be visualized across the age range in a spatiotemporally detailed time-lapse sequence. The resulting time-lapse "movies" reveal that (i) higher-order association cortices mature only after lower-order somatosensory and visual cortices, the functions of which they integrate, are developed, and (ii) phylogenetically older brain areas mature earlier than newer ones. Direct comparison with normal cortical development may help understanding of some neurodevelopmental disorders such as childhood-onset schizophrenia or autism.
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Non-conscious processes involved in the formulation, organization, and expression of thought and consciousness are examined. It is argued that non-organized impulses and imageless non-linguistic knowledge exist prior to and result in the organization recognized as consciousness and thought. Hence consciousness is viewed as the developmental endpoint of a unitary process originating as non-activated sensations and knowledge, i.e., awareness. Because one can be aware of and have knowledge of “things” prior to being conscious of them, it is possible to know, yet not know, or rather not think about certain objectionable feelings or tacit ideas. These imageless, non-linguistic forms of knowledge are not unconscious; rather they are non-labeled and non-descriptive. Within this framework the Freudian conception of unconscious processes is examined and shown to support a model of self-deception, defined as a conscious refusal to attend to unstructured tacit knowledge of which one is simultaneously aware.
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Describes the earth's physical characteristics, discussing interactions of climate, geology, and ecology.
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The volume of the temporal lobe, superior temporal gyrus, amygdala, and hippocampus was quantified from magnetic images of the brains of 99 healthy children and adolescents aged 4–18 years. Variability in volume was high for all structures examined. When adjusted for a 9% larger total cerebral volume in males, there were no significant volume differences between sexes. However, sex-specific maturational changes were noted in the volumes of medial temporal structures, with the left amygdala increasing significantly only in males and with the right hippocampus increasing significantly only in females. Right-greater-than-left laterality effects were found for temporal lobe, superior temporal gyrus, amygdala, and hippocampal volumes. These results are consistent with previous preclinical and human studies that have indicated hormonal responsivity of these structures and extend quantitative morphologic findings from the adult literature. In addition to highlighting the need for large samples and sex-matched controls in pediatric neuroimaging studies, the information from this understudied age group may be of use in evaluating developmental hypotheses of neuropsychiatric disorders. © 1996 Wiley-Liss, Inc.†
Article
Total midsagittal area and seven subdivisions of the corpus callosum were measured on magnetic resonance images of 114 healthy boys and girls, aged 4 to 18. Striking variability of size was noted for all measures. Total midsagittal corpus callosum area increased in a robust and linear fashion from ages 4 to 18 (slope = 13.1 mm2/year, P = 0.0001 and slope = 11.1 mm2/year, P = 0.0001 for females and males, respectively). Posterior and mid regions demonstrated greater age-related changes than anterior regions with the rostrum and genu (anterior regions) having reached adult sizes in the youngest of our subjects. There were no significant effects of sex for any measures. These findings support anatomical studies indicating ongoing myelination of higher association areas throughout adolescence, but raise intriguing questions about anterior-posterior gradients of interhemispheric myelination.
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Segmentation of the intracranial cavity in medical images is valuable in several research areas such as the quantitative analysis of normal and abnormal brain tissues, the registration of different imaging modalities (MRI, PET, CT) based on surface models of the brain, and the rendering of volume data. Because the manual delineation of the brain contour in the images can be demanding and error prone, an automatic procedure to perform this task is desirable. We have developed and tested a robust method that permits the automatic detection of the intracranial contour in transverse MR images. The method is described and its performance evaluated.
Article
Previous experiments found that concurrently maintaining verbal information in memory influences visual laterality patterns. The present article reviews existing studies and reports 5 additional experiments (434 undergraduate Ss) designed to identify the mechanisms responsible for such effects. Exp I demonstrated that laterality patterns were not influenced by a concurrent memory task that did not require verbal processing. (The verbal nature of the concurrent task was an important aspect of previous experiments.) Exps II and III were designed to determine whether concurrent verbal memory primarily influences early visuospatial processes or later processes such as those involved in visuospatial memory. Results suggest that concurrent verbal memory influences stages of processing beyond the initial registration of visuospatial information. Exps IV and V examined the influence of concurrent verbal memory on verbal laterality tasks. Results show that concurrent verbal memory influences processing stages beyond those that are common to the form-pair and letter-pair tasks. Neither directness-of-pathway nor attention-gradient laterality models can explain the entire pattern of results from the present experiments. Results suggest that the left hemisphere functions as a typical limited-capacity information processing system that can be influenced somewhat separately from the right hemisphere system. (65 ref) (PsycINFO Database Record (c) 2006 APA, all rights reserved).
Article
The long-term effects of cerebral commissurotomy on motor co-ordination and dyspraxia were investigated in 8 patients who had undergone complete or partial commissurotomy 5-10 yr previously. Performance on a series of standardized motor co-ordination and manual dexterity tests was compared with the established norms. Although qualitative performance appeared essentially unimpaired on most tests the scores for speed were consistently below normal and also inferior to those reported for patients with various unilateral brain lesions. In certain bimanual tasks requiring rapid alternating motion and interdependent control severe qualitative and quantitative impairments were present. In addition, marked dysgraphia and mild ideomotor-type dyspraxia on the left side, and moderate dyscopia on the right were present up to 10 yr after surgery in patients with complete commissurotomy. It would appear from the results that interhemispheric communication becomes particularly important for motor output to the extent that the tasks involve complex intermanual coordination or hemispheric specialization with ipsilateral control.
Article
In this report, earlier findings of age-related changes in brain morphology on magnetic resonance (MR) images are extended to include measurements of individual cerebral grey matter structures and an index of white matter degeneration. Volumes of caudate, lenticular, and diencephalic structures are estimated, as are grey matter volumes in eight separate cortical regions. Results suggest that between 30 and 79 years significant decreases occur in the volume of the caudate nucleus, in anterior diencephalic structures, and in the grey matter of most cortical regions. The data suggest that the volumes of the thalamus and the anterior cingulate cortex may be unchanged. Among those cortical regions found to be affected in aging, some evidence is present for greater change in association cortices and mesial temporal lobe structures. There are also dramatic age-related changes in the white matter, manifest as lengthened T2 values on MR images.
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Fossil, comparative anatomic and ontogenic data suggest that several systems of functionally and anatomically related brain regions underwent selective expansion or differentiation during primate evolution, according to the principle of 'integrated phylogeny'. This process was closely tied to expansion of the neocortex, particularly of its association areas. System I regions include the association neocortices as well as the nucleus basalis of Meynert, the entorhinal cortex, and subdivisions of the septum, hippocampal formation and amygdaloid complex. This system undergoes degeneration in Alzheimer's and Pick's diseases and Down syndrome. System II includes segregated circuits involving parts of the frontal cortex, basal ganglia, thalamus, and substantia nigra, and can become defective in obsessive-compulsive disorder, Huntington's and Parkinson's diseases. Certain nuclei in the mesencephalon and brainstem, which co-evolved with System I and II regions, also demonstrate pathology in diseases affecting these systems. Integrated phylogeny of each of these systems during primate evolution likely was promoted by regulatory mutations, gene duplications or chromosomal rearrangements. Thus, understanding the genetic basis of integrated phylogeny of systems of brain regions during primate evolution may elucidate the pathogenesis of the human diseases which affect these regions.
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This study examined the specificity of deviations in patterns of normal brain asymmetry on the magnetic resonance imaging scans of 10 dyslexic, 10 attention deficit disorder/hyperactivity (ADD/H), and 10 normal age- and sex-matched control children. Reliabilities of region of interest measurements for left and right anterior and posterior width and area, length of the bilateral insular region, and length of the bilateral planum temporale were excellent. Both the dyslexic and ADD/H children had significantly smaller right anterior-width measurements than did normal subjects. The dyslexics also had a bilaterally smaller insular region and significantly smaller left planum temporale than did the normal subjects. Seventy percent of the normal and ADD/H children had the expected left greater than right pattern of plana asymmetry, while only 10% of the dyslexic children did. The very significant increase in the incidence of plana symmetry or reversed asymmetry seems unique to dyslexia and may be related to deviations in normal patterns of corticogenesis. Although significantly more dyslexic children were left-handed than were the normal and ADD/H children, no significant relationship emerged between left-handedness, incidence of allergies or familial autoimmune disease, and variability in indexes of brain morphologic findings.
Article
Estrogen receptor (ER) levels were measured in brain tissue cytosol from fetal male and female rhesus monkeys at Days 70, 100 and 160 postconception. The brain regions which were examined included medial basal hypothalamus (MBH), amygdala (AMG), cerebral cortex (CTX) and cerebellum (CB). For comparison, brain tissues were also obtained from an adult female, and muscle (MUS) and genital tract (GEN, ovaries + uterus) ER values were measured in several Day 70 fetuses. Tissues were dissected and homogenized as previously described. Cytosol was passed through a microcolumn of Lipidex 1000 to remove interfering lipids and incubated with [3H]Moxestrol (4 nM) in the presence or absence of 500 nM Moxestrol. Incubations were carried out for 24 h at 4 degrees C, and free and bound ligand separated by Sephadex LH-20 gel filtration. In one case (Day 160 male fetus), saturation analysis yielded an estimate of apparent Kd of 0.46 x 10(-9) M and indicated that maximal specific binding was achieved at a ligand concentration of 1-2 nM. There was no sex difference at any stage of development (ANOVA). A significant age effect (P less than 0.002) was noted for the MBH and CB but not for any of the other tissues examined. In the MBH the significance of this effect was due to a progressive increase in ER levels with fetal age and into adulthood. In contrast, CB levels exhibited a progressive decline with age. These studies revealed that the ER is present during brain development. Thus any estrogens derived from the aromatization of circulating fetal androgens could potentially exert an influence upon brain development.(ABSTRACT TRUNCATED AT 250 WORDS)
Article
The influence of gonadal steroids on the maturation of the cerebral cortex and their possible influence on cortical function are not well understood. The present study examines androgen binding and metabolism in regions of the cerebral cortex and several subcortical structures at different time points during the development of the rhesus monkey. Androgen binding and metabolism were assessed in selected cortical and subcortical regions from neonatal, juvenile, and adult rhesus monkeys. Specific high affinity androgen-binding sites (apparent equilibrium dissociation constants for [3H]R1881, 0.04-0.3 nM) were observed in many areas of the rhesus monkey brain. These areas included (but were not limited to) the hypothalamus, amygdala, dorsolateral prefrontal cortex, orbital prefrontal cortex, visual and somatosensory cortex, and corpus callosum. Although the highest level of androgen binding was observed in the hypothalamus (8-20 fmol/mg protein), cortical samples also had measurable levels of binding (1-5 fmol/mg protein). No apparent regional or developmental differences in the number or affinity of androgen-binding sites were detected in animals ranging from 1 week to 8 yr in age. Androgen metabolism via aromatization and 5 alpha-reduction was observed in all regions of the neocortex examined, although at lower levels than in the hypothalamus and amygdala. Overall production of estrogens and 5 alpha-reduced androgens declined approximately 10-fold from prenatal to early postnatal life in both cortical and subcortical structures. The presence of androgen binding and metabolism in the monkey cerebral cortex indicates that steroid hormones may have considerable impact on cortical function in primates at postnatal as well as prenatal ages.
Article
Young adult Sprague-Dawley rats of either sex were randomly assigned to be gonadectomized or left intact. Capsules containing either testosterone or estrogen were implanted in animals in both categories. Fifteen days after removal of the entorhinal cortex, the brains were analyzed for changes in reactive outgrowth of the commissural-associational afferent fibers in the hippocampal dentate gyrus. Both male and female control subjects showed identical sprouting responses. Only female subjects were significantly affected by gonadectomy, resulting in significant decreases in reactive fiber outgrowth. Hormone replacement therapy resulted in a return to control values in castrated females but had no affect on castrated males. The results suggest that sex hormones may regulate axon sprouting in the mature central nervous system.
Article
In fifteen awake, chronic cats single-unit recordings were obtained from 316 fibres isolated in the rostral portion of the corpus callosum (CC). Altogether, 304 units were reactive to peripheral stimuli. They were fired by hair bending, light touch or light pressure (S units; 79.3%) or by gentle rotation of joints and/or by pressure on muscle bellies or tendons (D units; 20.7%). All the reactive units were endowed with small and unilateral receptive fields (RFs) located in trigeminal (49.7%) or segmental (50.3%) regions. Trigeminal and forepaw units had the smallest RFs. All the trigeminal units were of the S type. Their RFs were located in either the ophthalmic, maxillar, and mandibular face districts or in the oral vestible. The vast majority of segmental units (146 out 153 fibres) had RFs in the forelimb. Very few units were fired by stimulation of the trunk (6 fibres), and only one had its RF in the tail. Almost half of the forelimb units (69 fibres) were fired by stimulation of the most proximal parts of the forelimb and of the shoulder; about one third (57 fibres) exhibited RFs located in the forepaw; the remaining units (20 fibres) had their RFs in the intermediate region of the forelimb. Neither the trigeminal nor segmental RFs ever extended across the midline. The distribution of the fibres within the CC conformed to a somatotopic pattern. The representations of the trigeminal and segmental regions were largely coextensive. Along the rostro-caudal axis of the CC, units with RFs in the mandibular, maxillar and ophthalmic divisions of the trigeminal region tended to lie in this order in the rostralmost 4 mm.(ABSTRACT TRUNCATED AT 250 WORDS)
Article
Ten commissurotomy patients (8 with complete and 2 with partial section of the forebrain commissures) obtained subnormal scores on a battery of 6 standardized tests for assessment of memory. Although the observed memory impairment is presumed to have been amplified by extracommissural brain damage in most of the cases, it is concluded that the loss of the cerebral commissures is mainly responsible and that these commissures serve selective mnestic functions. In particular the data suggest that processes mediating the initial encoding of engrams and the retrieval and read out of contralateral engram elements involve hemispheric cooperation and depend upon the function of the interhemispheric commissures.
Article
Summary 1. In the rostral part of the corpus callosum (somesthetic callosal region, SCR) fibres were identified, through which the callosally-projecting cells of the somatosensory areas transmit to the other hemisphere signals originated in the body surface. 2. With seriate macroelectrode penetrations it was found that, to some extent, the body surface is represented somatotopically in the rostrocaudal extent of the SCR. The strongest mass potentials to trigeminal, fore- and hindlimb stimulation were recorded from the rostral, middle and caudal portions of the SCR. The whisker region and the forelimb (both paws and proximal segments) appeared to have the widest callosal representation. 3. Ablation experiments showed that callosal somesthetic fibres originate in both SI and SII areas and that only impulses set up in the contralateral hemibody are relayed in these areas. Direct stimulation of the latter evoked within the SCR mass potentials whose rostrocaudal distribution parallels that of the peripherally evoked responses. 4. Exploring the SCR with microelectrodes, 43 spontaneously active fibres were isolated, all reactive to electrical and physiological stimulation of the related peripheral receptive fields. These were located in trigeminal (31 fibres), segmental (10 fibres) or both in trigeminal and segmental regions (2 fibres). The extent of the receptive fields and the reactivity characteristics of almost all the fibres sampled were lemniscal in type, and similar to those of the somatotopic neurones of cortical somatosensory areas.