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Intolerance of Uncertainty Predicts Increased Striatal Volume
Abstract
Oversensitivity to uncertain future threat is usefully conceptualized as intolerance of uncertainty (IU). Neuroimaging studies of IU to date have largely focused on its relationship with brain function, but few studies have documented the association between IU and the quantitative properties of brain structure. Here, we examined potential gray and white-matter brain structural correlates of IU from 61 healthy participants. Voxel-based morphometric analysis highlighted a robust positive correlation between IU and striatal volume, particularly the putamen. Conversely, tract-based spatial statistical analysis showed no evidence for a relationship between IU and the structural integrity of white-matter fiber tracts. Current results converge upon findings from individuals with anxiety disorders such as obsessive-compulsive disorder (OCD) or generalized anxiety disorder (GAD), where abnormally increased IU and striatal volume are consistently reported. They also converge with neurobehavioral data implicating the putamen in predictive coding. Most notably, the relationship between IU and striatal volume is observed at a preclinical level, suggesting that the volumetric properties of the striatum reflect the processing of uncertainty per se as it relates to this dimensional personality characteristic. Such a relationship could then potentially contribute to the onset of OCD or GAD, rather than being unique to their pathophysiology. (PsycINFO Database Record
... In their study towards sports sciences students, Sarı et al. found that age variable was not a significant difference in terms of need for relationship [24]. Recently in a study of Kim published in Emotion by APA Publishing, it was detected that people who struggled with the potential uncertainness of future and its lexical blur (or people felt he/she had to overcome) and saw this uncertainness of future as a threat had an extremely big stratum area [25]. This brain area called stratum was known for its relation with general anxiety and anxiety disorder according to the previous studies and data. ...
... This brain area called stratum was known for its relation with general anxiety and anxiety disorder according to the previous studies and data. In the study published by American Psychological Association, Kim revealed that there was a connection between individual's overcoming of uncertainness of future / not seeing this as a problem and the intensity of gray matter in a certain area of the brain [25]. Fear of failure is a part of the domination struggle on our important issues, and it is inevitable and innate [26]. ...
Purpose: This research was carried out in order to analyze elite athletes’ aim orientation, basic psychological needs and fear of failure in perspective of several variables, and to reveal the differences among these variables. Material and Methods: Sample of the research consisted of elite athletes from different branches who had been in different regions of Turkey in 2016-2017. Number of elite athletes in this research was (n=521) in total, 378 of whom were males and 173 of whom were females. These elite athletes had been chosen by random sampling. As data collection tools, Basic Psychological Needs Scale, which was adapted to Turkish by Kesici et al (2003), Fear of Failure Scale which was adapted to Turkish by Kahraman and Sungur (2016), Scale of Task and Ego Orientation in Sports that was adapted to Turkish by Toros (2004) were used in the study. Results. It was concluded that females had lower fear of “unclear future” and “experiencing shame and embarrassment” than males. It was revealed that as the age of the participants went up, their needs for relationship, fear of unclear future, fear of experiencing shame and embarrassment, and task orientation increase. It was found out that participants who had direct branches had higher “need for relationship” and “fear of unclear future” in comparison with the ones who had indirect branches. Conclusion: According to the results of the study, it was found that there was meaningful difference in sub-dimensional fear of failure in terms of gender variable, in sub-dimensional fear of failure, in basic psychological needs and in aim orientation with regards to age variable, in sub-dimensional basic psychological needs and in fear of failure in terms of branch variation (direct - indirect) variable.
... They found that Cluster C personality disorder symptoms were related to larger striatal surface area localized to the caudate tail, reduced ventral striatum volumes, and larger cortical thickness in the right prefrontal cortex compared to healthy comparison subjects whereas both Cluster B and C personality disorder symptoms were associated with trends to larger posterior caudate volumes and orbitofrontal surface area abnormalities, concluding that morphological abnormalities could be extensively contributing to Cluster C personality disorder symptoms. Kim et al. [9] studied potential gray and white matter brain structural correlates of intolerance of uncertainty, which is an important clinical characteristic of patients with OCPD, in sixty one healthy subjects. They examined them by using voxel-based morphometric analysis and revelaed a clear positive correlation between intolerance of uncertainty and striatal volume, especially the putamen, considering that the volumetric properties of the striatum might reflect the processing of uncertainty per se. ...
... They found that Cluster C personality disorder symptoms were associated with larger striatal surface area localized to the caudate tail, reduced ventral striatum volumes, and larger cortical thickness in the right prefrontal cortex compared to healthy comparison subjects whereas both Cluster B and C personality disorder symptoms were related to trends to larger posterior caudate volumes and orbitofrontal surface area abnormalities, indicating that morphological abnormalities could be extensively contributing to Cluster C personality disorder symptoms. By the way, Kim et al. [9] investigated potential gray and white matter brain structural correlates of intolerance of uncertainty, which is an important clinical characteristic of patients with OCPD, and found a clear positive correlation between intolerance of uncertainty and striatal volume, especially the putamen, considering that the volumetric properties of the striatum might reflect the processing of uncertainty per se. All studies on patients with OCPD are limited to those mentioned above. ...
Objectives
Obsessive compulsive personality disorder (OCPD) is currently thought to bear a close relationship with obsessive-compulsive disorder (OCD), and other compulsive disorders such as eating disorder and autistic spectrum disorder, as well as with the personality disorders, focusing on some important dimensions like phenomenology, heritability, environmental risk factors, comorbidity, course of illness, neurocognitive endophenotypes, and treatment response. In the present study, when we have taken into consideration the knowledge aforementioned, we aimed to examine OFC and thalamus volumes in patients with OCPD.
Methods
We comparatively measured orbito-frontal cortex (OFC) and thalamus volumes of patients with OCPD and healthy control subjects.
Results
Patients with OCPD had considerably smaller left and right OFC volumes compared to those of healthy control subjects. We also found that thalamus volumes of patients were statistically significantly greater than those of healthy comparisons for both sides of region of interest.
Conclusions
We consider that volumetric alterations determined in the present study may be involved in the pathophysiology of the OCPD, considering that OCPD might be related to OCD spectrum disorders neuroanatomically.
... One explanation for this discrepancy is that reductions in reward processing could be a result of prolonged stress and behavioral dysfunctions leading to reductions in perceived control similar to that observed in depression; whereas increased striatal activation and volume could reflect an increased desire for control in aversive or ambiguous contexts. For instance, increased striatal activation and volume in relation to anxiety could be associated with increased vigilance for threat, or an intolerance for uncertainty (Ly et al., 2013;Kim et al., 2017). One clinical feature that is more uniquely related to anxiety is the fear of losing control. ...
... One clinical feature that is more uniquely related to anxiety is the fear of losing control. An intolerance for uncertainty and disrupted contingency learning in a dynamic environment in relation to anxiety (Browning et al., 2015;Kim et al., 2017;Piray et al., 2018), might together explain this fear of losing control as well as the subsequent maladaptive forms of control-seeking behavior, such as avoidance and compulsive behavior. ...
Perceived control can be broadly defined as the belief in one’s ability to exert control over situations or events. It has long been known that perceived control is a major contributor toward mental and physical health as well as a strong predictor of achievements in life. However, one issue that limits a mechanistic understanding of perceived control is the heterogeneity of how the term is defined in models in psychology and neuroscience, and used in experimental settings across a wide spectrum of studies. Here, we propose a framework for studying perceived control by integrating the ideas from traditionally separate work on perceived control. Specifically, we discuss key properties of perceived control from a reward-based framework, including choice opportunity, instrumental contingency, and success/reward rate. We argue that these separate reward-related processes are integral to fostering an enhanced perception of control and influencing an individual’s behavior and well-being. We draw on select studies to elucidate how these reward-related elements are implicated separately and collectively in the investigation of perceived control. We highlight the role of dopamine within corticostriatal pathways shared by reward-related processes and perceived control. Finally, through the lens of this reward-based framework of perceived control, we consider the implications of perceived control in clinical deficits and how these insights could help us better understand psychopathology and treatment options.
... Additionally, Hilbert et al. (2015) found that IU and gray matter volume in the striatum were positively correlated. Although the correlation did not survive a conservative correction for multiple comparisons, recent findings from Kim et al. (2017) have also documented a positive correlation between gray matter volume in the striatum-particularly the putamen-and IU. Given that the striatum is involved in encoding how predictable and expected outcomes are, the authors suggest that higher striatal volume associated with IU may reflect a neuroanatomical correlate of heightened desire for predictability (Kim et al., 2017). ...
... Although the correlation did not survive a conservative correction for multiple comparisons, recent findings from Kim et al. (2017) have also documented a positive correlation between gray matter volume in the striatum-particularly the putamen-and IU. Given that the striatum is involved in encoding how predictable and expected outcomes are, the authors suggest that higher striatal volume associated with IU may reflect a neuroanatomical correlate of heightened desire for predictability (Kim et al., 2017). ...
Intolerance of uncertainty (IU) reflects the perception of uncertainty as threatening, regardless of the true probability of threat. IU is elevated in various forms of psychopathology, uniquely associated with anxiety and depression symptoms after controlling for related constructs, and prospectively predicts symptoms. Given the ubiquity of uncertainty in daily life and the clinical implications of IU, recent work has begun to investigate the neural and psychophysiological correlates of IU. This review summarizes the existing literature and integrates findings within a mechanistic neural model of responding to uncertainty. IU is associated with heightened reactivity to uncertainty reflected in greater activity of the anterior insula and amygdala, alterations in neural responses to rewards and errors evident in event-related potentials, a mixed pattern of startle responses to uncertain threat, and deficiencies in safety learning indexed by startle and skin conductance responding. These findings provide evidence of disruptions in several domains of responding to uncertainty, threat, and reward associated with IU that may confer risk for the development of psychopathology. Significant attention is devoted to recommendations for future research, including consideration of the complex interplay of IU with emotion regulation, cognitive control, and reward processing.
... The putamen is part of the dorsal striatum and has been related to anxiety disorders and anxiety symptoms [150,151]. For example, a previous VBM study indicated a positive relationship between intolerance of uncertainty, a psychological construct related to anxiety, and bilateral striatal volume, in particular the putamen [152]. In contrast, some evidence suggests a negative correlation between putamen volume and the severity of PD symptoms [67]. ...
Internalizing disorders encompass anxiety, fear and depressive disorders, which exhibit overlap at both conceptual and symptom levels. Given that a neurobiological evaluation is lacking, we conducted a Seed-based D-Mapping comparative meta-analysis including coordinates as well as original statistical maps to determine common and disorder-specific gray matter volume alterations in generalized anxiety disorder (GAD), fear-related anxiety disorders (FAD, i.e., social anxiety disorder, specific phobias, panic disorder) and major depressive disorder (MDD). Results showed that GAD exhibited disorder-specific altered volumes relative to FAD including decreased volumes in left insula and lateral/medial prefrontal cortex as well as increased right putamen volume. Both GAD and MDD showed decreased prefrontal volumes compared to controls and FAD. While FAD showed less robust alterations in lingual gyrus compared to controls, this group presented intact frontal integrity. No shared structural abnormalities were found. Our study is the first to provide meta-analytic evidence for distinct neuroanatomical abnormalities underlying the pathophysiology of anxiety-, fear-related and depressive disorders. These findings may have implications for determining promising target regions for disorder-specific neuromodulation interventions (e.g. transcranial magnetic stimulation or neurofeedback).
... In their recent review Levy and Schiller (2021) showed that the striatum is not only associated with avoidance, but also with decision making and uncertainty. Similarly, Justin Kim et al. (2017) provided evidence that grey matter volume in the bilateral putamen is correlated with IU scores. Our findings about Table 3 Group comparisons (low vs. high IU/TA) of fMRI BOLD activation during reinstatement test phase and re-extinction phase. ...
It is hypothesized that the ability to discriminate between threat and safety is impaired in individuals with high dispositional negativity, resulting in maladaptive behavior. A large body of research investigated differential learning during fear conditioning and extinction protocols depending on individual differences in intolerance of uncertainty (IU) and trait anxiety (TA), two closely-related dimensions of dispositional negativity, with heterogenous results. These might be due to varying degrees of induced threat/safety uncertainty. Here, we compared two groups with high vs. low IU/TA during periods of low (instructed fear acquisition) and high levels of uncertainty (delayed non-instructed extinction training and reinstatement). Dependent variables comprised subjective (US expectancy, valence, arousal), psychophysiological (skin conductance response, SCR, and startle blink), and neural (fMRI BOLD) measures of threat responding. During fear acquisition we found strong threat/safety discrimination for both groups. During early extinction (high uncertainty), the low IU/TA group showed an increased physiological response to the safety signal, resulting in a lack of CS discrimination. In contrast, the high IU/TA group showed strong initial threat/safety discrimination in physiology, lacking discriminative learning on startle, and reduced neural activation in regions linked to threat/safety processing throughout extinction training indicating sustained but non-adaptive and rigid responding. Similar neural patterns were found after the reinstatement test. Taken together, we provide evidence that high dispositional negativity, as indicated here by IU and TA, is associated with greater responding to threat cues during the beginning of delayed extinction, and, thus, demonstrates altered learning patterns under changing environments.
... We know that individuals differ in their attitudes towards uncertainty and that this affects behavioural and physiological markers of anxiety, but how does this shape their neural responses? The few structural studies that have examined this have observed increased grey matter volume in the right superior temporal pole in high IUS individuals (Hilbert et al., 2015) and a positive correlation between striatal volume, especially in the putamen specifically and IUS (Kim et al., 2017), although further research is needed to determine the relationship between this region and others that show functional differences. Further studies have highlighted differences in functional neural activity in high IUS individuals. ...
Anxiety disorders are the most common mental health disorders and comprise a large number of years lost to disability. The work in this thesis is oriented towards understanding anxiety using a computational approach, focusing on uncertainty estimation as a key process. Chapter 1 introduces the role of uncertainty within anxiety and motivates the subsequent experimental chapters. Chapter 2 is a review of the computational role of the amygdala in humans, a key area for uncertainty computation. Chapter 3 is an experimental chapter which aimed to address gaps in the literature highlighted in the preceding chapters, namely the link between sensory uncertainty processing and anxiety and the role of the amygdala in this process. This chapter focuses on the development of a novel computational hierarchical Bayesian model to quantify sensory uncertainty and its application to neuroimaging data, with intolerance of uncertainty relating to greater neural activation in the insula but not amygdala. Chapter 4 targets the computational mechanisms underlying the negative self-bias observed in subclinical social anxiety. Again, this chapter focuses on the development of novel computational belief-update models which explicitly model uncertainty. Here, we see that a reduced trait self-positivity underpins this negative social evaluation process. The final experimental chapter presented in Chapter 5 investigates the link between different computational mechanisms, such as uncertainty, and a range of mood and anxiety symptomatology. This study revealed cognitive, social and somatic computational profiles that share a threat bias mechanism but have distinct negative-self bias and aversive learning signatures. Contrary to expectations, none of the uncertainty measures showed any associations with anxiety symptom subtypes. Finally, chapter 6 brings together the work in this thesis and alongside limitations of the work, discusses how these experiments contribute to our understanding of anxiety and the role of uncertainty across the anxiety spectrum.
... In their recent review Levy and Schiller (2021) showed that the striatum is not only associated with avoidance, but also with decision making and uncertainty. Similarly, Justin Kim et al. (2017) provided evidence that grey matter volume in the bilateral putamen is correlated with IU scores. Our findings about Table 3 Group comparisons (low vs. high IU/TA) of fMRI BOLD activation during reinstatement test phase and re-extinction phase. ...
It is hypothesized that the ability to discriminate between threat and safety is impaired in individuals with high dispositional negativity, resulting in maladaptive behavior. A large body of research investigated differential learning during fear conditioning and extinction protocols depending on individual differences in intolerance of uncertainty (IU) and trait anxiety (TA), two closely-related dimensions of dispositional negativity, with heterogenous results. These might be due to varying degrees of induced threat/safety uncertainty. Here, we compared two groups with high vs. low IU/TA during periods of low (instructed fear acquisition) and high levels of uncertainty (delayed non-instructed extinction training and reinstatement). Dependent variables comprised subjective (US expectancy, valence, arousal), psychophysiological (skin conductance response, SCR, and startle blink), and neural (fMRI BOLD) measures of threat responding. During fear acquisition we found strong threat/safety discrimination for both groups. During early extinction (high uncertainty), the low IU/TA group showed an increased physiological response to the safety signal, resulting in a lack of CS discrimination. In contrast, the high IU/TA group showed strong initial threat/safety discrimination in physiology, lacking discriminative learning on startle, and reduced neural activation in regions linked to threat/safety processing throughout extinction training indicating sustained but non-adaptive and rigid responding. Similar neural patterns were found after the reinstatement test. Taken together, we provide evidence that high dispositional negativity, as indicated here by IU and TA, is associated with greater responding to threat cues during the beginning of delayed extinction, and, thus, demonstrates altered learning patterns under changing environments.
... This retrieval technology based on image features overcomes the defects of text-based retrieval methods, greatly improves the retrieval rate and efficiency, and gradually becomes a hot spot in the field of image retrieval. In recent years, extensive research has been conducted on image detection based on striation characteristics, and its methods are mainly summarized as the statistical method, model method, signal processing method, and structure method [4]. Literature [5] puts forward the concept of the cooccurrence matrix in image space. ...
A new document image retrieval algorithm is proposed in view of the inefficient retrieval of information resources in a digital library. First of all, in order to accurately characterize the texture and enhance the ability of image differentiation, this paper proposes the statistical feature method of the double-tree complex wavelet. Secondly, according to the statistical characteristic method, combined with the visual characteristics of the human eye, the edge information in the document image is extracted. On this basis, we construct the meaningful texture features and use texture features to define the characteristic descriptors of document images. Taking the descriptor as the clue, the content characteristics of the document image are combined organically, and appropriate similarity measurement criteria are used for efficient retrieval. Experimental results show that the algorithm not only has high retrieval efficiency but also reduces the complexity of the traditional document image retrieval algorithm.
... We consider two such models. The first, which we term the quantitative model, stems from how valence variability is treated in Mattek et al.'s (2017) original analysis of emotional ambiguity. There, the authors relied on the intuitive idea that when subjects rate items' valence, the uncer-tainty of the ratings is inversely related to their intensity. ...
The emotional ambiguity hypothesis introduced the principle that uncertainty about items' valence determines how emotional content affects memory and other psychological processes. It was formulated to explain why correlations between the perceived valence and arousal of memory items range from weak to unreliable, but it also makes novel predictions. Although data are consistent with those predictions, the hypothesis does not provide a process model of how valence ambiguity causes the valence-arousal relation to fluctuate. We tested 2 such models-a quantitative one, which assumes that increasing ambiguity lowers the reliability of valence judgments, and a categorical/quantitative one, which assumes that increasing ambiguity restricts the range of valence judgments. These models predict different mathematical relations between measures of ambiguity and intensity for valence and other semantic attributes (e.g., arousal, concreteness, familiarity, imagery, meaningfulness). In Experiments 1-3, tests of those predictions favored the categorical/quantitative model-showing that ambiguity is an inverted-U function for valence and other attributes. Experiments 4 and 5 were designed to investigate whether the memory effects of valence ambiguity are similar to the known effects of valence intensity. In both experiments, recall improved when ambiguity was increased, as well as when intensity was increased. A mathematical model revealed that increases in ambiguity produced large increases in items' familiarity, whereas increases in intensity produced smaller increases in both recollection and familiarity. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
... Notably, the role of the striatum has-until recently-received limited attention in these models (97). Although often thought of in relation to its role in reward systems, it also links to several anxiety processes (e.g., attention bias, fear conditioning, motivation, intolerance of uncertainty) (97,98). The striatum is functionally linked to components of fear circuitry, particularly in the context of stress reactivity (99), and has strong interactive effects with the amygdala (100). ...
Avoidant behavior is a defining feature of pediatric anxiety disorders. Although prior research has examined it from the perspective of early information processing events, there has been relatively less consideration of the processes by which anxious youth make avoidant decisions and how these choices are reinforced over time. Studies of risk taking are valuable in this regard as they consider how individuals identify the pros and cons of their choices, how they weight potential gains and losses and estimate their respective probabilities, and how they tolerate the uncertainty intrinsic to any decision. In this review, we place risk taking within existing models of information processing in pediatric anxiety disorders and highlight the particular value of this construct for informing models of developmental psychopathology and individual differences in outcome over time. We review existing behavioral and neurobiological studies of risk taking in anxious youth and conclude by identifying directions for future research.
... Смугасте тіло, що складається з хвостатого ядра та лушпини, відповідає за прийняття рішень, на основі оцінки очікуваної винагороди. Так як смугасте тіло відповідає за прагнення до передбачуваності [4], послуговуючись індуктивним методом можна спрогнозувати, що виборці із збільшеним об'ємом стріатуму надаватимуть перевагу політичним силам консервативного спрямування. Передбачуваність є еволюційним наступником інстинкту самозбереження або філософської категорії «турботи». ...
Актуальні проблеми політології
... While future work is needed to examine whether this association holds in juvenile rats, the striatum has also been linked to anxiety in humans; anxious youth show greater striatal response to lowrather than high-valued outcomes, perhaps due to the relative level of potential risk associated with each option, in addition to demonstrating increased VS activity during feedback anticipation . Furthermore, an intolerance of uncertainty-a common feature of anxiety (Dekkers et al., 2017;Osmanağaoğlu et al., 2018)-has been positively associated with striatal volume (Kim et al., 2017). ...
Anxiety is common in adolescence and has been linked to a plethora of negative outcomes across development. While previous studies of anxiety have focused on threat sensitivity, less work has considered the concurrent development of threat- and reward-related neural circuitry and how these circuits interact and compete during puberty to influence typical adolescent behaviors such as increased risk taking and exploration. The current review integrates relevant findings from clinical and developmental neuroimaging studies to paint a multidimensional picture of adolescent-onset anxiety against the backdrop of typical adolescent development. Ultimately, this paper argues that longitudinal neuroimaging studies tracking approach and avoidance motivations across development are needed to fully understand the mechanisms underlying the development of anxiety in adolescence and to identify and provide effective interventions for at-risk youth.
... Activation in the dorsal striatum (head and tail of the caudate nucleus, putamen) has been implicated in the formation of stimulus-action-reward associations [9], motivation and arousal [46]. Dorsal striatum was associated to Interneuron depletion in SAD [10], increased activation as incentive magnitude increased in the social phobia group [47], altered functional connectivity [48] and putamen volume correlated with intolerance of uncertainty [49]. Finally, Bas-Hoogendam et al., (2017), in their international multi-center mega-analysis on the largest database (n=174) of SAD to date, identified putamen as the only region where higher gray matter (GM) volume was observed. ...
Social Anxiety Disorder (SAD) is characterized by emotional and attentional biases as well as distorted negative self-beliefs. According this, we proposed to identify the brain structures and hub genes involved in SAD. An analysis in Pubmed and TRANSFAC was conducted and 72 genes were identified. Using Microarray data from Allen Human Brain Atlas it was possible to identify three modules of co-expressed genes from our gene set (R package WGCNA). Higher mean gene expression was found in cortico-medial group, basomedial nucleus, ATZ in amygdala and in head and tail of the caudate nucleus, nucleus accumbens and putamen in striatum. Our enrichment analysis identified the followed hub genes: DRD2, HTR1A, JUN, SP1 and HDAC4. We suggest that SAD is explained by delayed extinction of circuitry for conditioned fear caused by reduced activation of the dopaminergic and serotonergic systems due diminished expectation of reward during social interactions.
... thickness in the right prefrontal cortex compared to healthy comparison subjects whle both Cluster B and C personality disorder symptoms were linked to trends to greater posterior caudate volumes and orbitofrontal surface area abnormalities, concluding that morphological abnormalities could be extensively contributing to Cluster C personality disorder symptoms. In addition, Kim et al. [9] evaluated the relationship between potential gray and white matter brain structures and intolerance of uncertainty, which is an important clinical aspect of patients with OCPD, in the healthy subjects who were sixty individuals. The authors investigated them by utilization of voxel-based morphometric analysis and reported a clear positive correlation between intolerance of uncertainty and striatal volume, particularly the putamen, considering that the volumetric properties of the striatum might reflect the processing of uncertainty per se. ...
Objectives:
Moving from the point that there might be an association between the neuroanatomy of obsessive-compulsive disorder (OCD) and obsessive-compulsive personality disorder, we decided to examine the volumes of hippocampus and amygdala of patients with obsessive-compulsive personality disorder, which was previously evaluated in OCD patients by us.
Methods:
Volumes of the hippocampus, and amygdala were measured by magnetic resonance imaging (MRI) in patients with obsessive-compulsive personality disorder and healthy control subjects. Manual tracing was used.
Results:
We detected that the mean left and right sides of hippocampus and amygdala volumes of the patients with obsessive-compulsive personality disorder were smaller than those of the healthy controls.
Conclusion:
Consequently, our present results suggest that hippocampal and amygdalar structural abnormalities may be related to the neuroanatomy of obsessive-compulsive personality disorder. However, it is required novel studies with larger sample.
... We don't agree with this statement: Potts and colleagues indicate that there is "no statistically significant difference between social phobia patients and normal control subjects"; the "age-related reduction in putamen volumes in patients with social phobia that was greater than that seen in controls" (25) cannot be equated with the group difference reported in the present metaanalysis. Furthermore, it should be noted that recent work on putamen volume in SAD, which was probably not yet available at the time the meta-analysis was performed, implies changes in the opposite direction, namely increased GMV in the dorsal striatum in SAD (14,16); these findings are supported by a positive relationship between social anxiety and GMV in the putamen in healthy women (26) and a positive correlation between the concept "intolerance of uncertainty" and putamen volume (27). ...
... This result is in line with findings of a mega-analysis on 174 patients with SAD and 213 healthy control participants, showing larger GM volume in the dorsal striatum, including the pallidum and the putamen; in this study, the increase in GM was positively related to the level of self-reported social anxiety [60]. Recently, the positive relationship between social anxiety and volume of the dorsal striatum was replicated in a sample of healthy young women with a broad range of social anxiety levels [67], while a study on the structural correlates of 'intolerance of uncertainty', a psychological construct that is related to anxiety, indicated a positive relationship between intolerance of uncertainty and bilateral striatal volume, in particular the putamen and pallidum [176]. Interestingly, these findings and the increase in pallidum volume reported in the present work fit within the recent focus on the striatum as being an important structure in the anxiety circuitry of the brain [177] and are potentially reflective of the role of the pallidum and putamen in processing emotions and reward [178], as both processes have been shown to be associated with altered brain activation levels in these regions in patients with SAD [170,[179][180][181]. ...
Background:
Social anxiety disorder (SAD) is a disabling psychiatric condition with a genetic background. Brain alterations in gray matter (GM) related to SAD have been previously reported, but it remains to be elucidated whether GM measures are candidate endophenotypes of SAD. Endophenotypes are measurable characteristics on the causal pathway from genotype to phenotype, providing insight in genetically-based disease mechanisms. Based on a review of existing evidence, we examined whether GM characteristics meet two endophenotype criteria, using data from a unique sample of SAD-patients and their family-members of two generations. First, we investigated whether GM characteristics co-segregate with social anxiety within families genetically enriched for SAD. Secondly, heritability of the GM characteristics was estimated.
Methods:
Families with a genetic predisposition for SAD participated in the Leiden Family Lab study on SAD; T1-weighted MRI brain scans were acquired (n = 110, 8 families). Subcortical volumes, cortical thickness and cortical surface area were determined for a-priori determined regions of interest (ROIs). Next, associations with social anxiety and heritabilities were estimated.
Findings:
Several subcortical and cortical GM characteristics, derived from frontal, parietal and temporal ROIs, co-segregated with social anxiety within families (uncorrected p-level) and showed moderate to high heritability.
Interpretation:
These findings provide preliminary evidence that GM characteristics of multiple ROIs, which are distributed over the brain, are candidate endophenotypes of SAD. Thereby, they shed light on the genetic vulnerability for SAD. Future research is needed to confirm these results and to link them to functional brain alterations and to genetic variations underlying these GM changes. FUND: Leiden University Research Profile 'Health, Prevention and the Human Life Cycle'.
Introduction:
This study investigates whether and how parental job insecurity motivates emerging adults' career networking behaviors. Using the framework of ecological system theory, we particularly focus on the sequential mediating role that overparenting behavior and emerging adults' intolerance of uncertainty could play.
Methods:
We recruit 741 fresh undergraduates (63.2% females) and their parents from the city of Jinan, Province Shandong in China. All of the participants are between the ages of 17 and 20 years. We apply a structural equation model using data obtained from multiple sources (i.e., fathers, mothers, and their children) at two time points to test our research model.
Results and conclusions:
The results from the structural equation model support the spillover effect of paternal and maternal job insecurity on overparenting behavior. Overparenting is significantly related to emerging adults' intolerance of uncertainty. In turn, emerging adults' intolerance of uncertainty is positively associated with their career networking behavior. The results also support the indirect effect, which demonstrates that parental job insecurity indirectly leads to emerging adults' career networking behavior via overparenting behavior and emerging adults' intolerance of uncertainty. This study builds on and extends existing research on parental job insecurity and career networking behavior by systematically bringing together the streams of research on youth development and organizational behavior. Specific theoretical implications and limitations are discussed as well.
Few individuals who experience trauma develop posttraumatic stress disorder (PTSD). Therefore, the identification of individual differences that signal increased risk for PTSD is important. Lissek et al. (2006) proposed using a weak rather than a strong situation to identify individual differences. A weak situation involves less-salient cues as well as some degree of uncertainty, which reveal individual differences. A strong situation involves salient cues with little uncertainty, which produce consistently strong responses. Results from fear conditioning studies that support this hypothesis are discussed briefly. This review focuses on recent findings from three learning tasks: classical eyeblink conditioning, avoidance learning, and a computer-based task. These tasks are interpreted as weaker learning situations in that they involve some degree of uncertainty. Individual differences in learning based on behavioral inhibition, which is a risk factor for PTSD, are explored. Specifically, behaviorally inhibited individuals and rodents (i.e., Wistar Kyoto rats), as well as individuals expressing PTSD symptoms, exhibit enhanced eyeblink conditioning. Behaviorally inhibited rodents also demonstrate enhanced avoidance responding (i.e., lever pressing). Both enhanced eyeblink conditioning and avoidance are most evident with schedules of partial reinforcement. Behaviorally inhibited individuals also performed better on reward and punishment trials than noninhibited controls in a probabilistic category learning task. Overall, the use of weaker situations with uncertain relationships may be more ecologically valid than learning tasks in which the aversive event occurs on every trial and may provide more sensitivity for identifying individual differences in learning for those at risk for, or expressing, PTSD symptoms.
Background:
The interval between adolescence and adulthood, 'emerging adulthood' (EA), lays the foundation for lifelong health and well-being. To date, there exist little empirical data - particularly in the neurobiological domain - to establish markers of risk and resilience during the transition to adulthood. This gap in the literature is concerning given the numerous forms of psychiatric illness that emerge or worsen during this period.
Methods:
In this review, we focus on two strands of research with distinct importance for EA: reward sensitivity, and tolerance of ambiguity. We begin by placing these domains in a framework that considers the unique developmental goals of EA and then synthesize emerging neurobiological research on how these domains develop during EA. We then consider their role in common mental health problems that occur during this interval as well as how social support may moderate outcomes. Finally, we offer recommendations for advancing research to understand developmental process and outcomes in EA.
Findings and conclusions:
Few longitudinal studies specifically address emerging adult development and the milestones that characterize this interval. Data on neurobiological development are similarly sparse. Understanding neurobiological development during this window and its links to key adjustment outcomes is crucial for optimizing outcomes.
The present chapter focuses on the neurobiology of obsessive-compulsive experiences in non-pathological and pathological contexts. The first part of the chapter reviews selected case studies of obsessive compulsive disorder (OCD) acquired as a result of neurological injury, obsessive-compulsive experiences experimentally evoked in otherwise healthy individuals, and obsessive-compulsive experiences and symptoms associated with specific physiological states and life events. The second part discusses several prominent neurobiological models for the pathophysiology of OCD, including the possible role of the cingulate cortex and action monitoring, the orbitofrontal cortex and the cortical attractor hypothesis, alterations in fear conditioning and safety signaling, imbalance of habit and goal-directed behavior, the Security Motivation System, and hypotheses involving dysfunctional processing of proprioceptive, interoceptive, and somatic marker information. The third part reviews existing treatment strategies for OCD: neurosurgery, neuromodulation, psychological, and pharmacological.
Thirty years ago, A. Ellis presented a revised ABC model. In this model, irrational beliefs (IBs) were considered as believing-emoting-behaving composite states. Consistent with A. Ellis’ proposals, in this chapter I describe embodied core IBs as embodied rigid motivational appraisals. The components and relevant processes of embodied rigid appraisals are defined. Fully activated embodied rigid appraisals are viewed as forms of anticipatory affect (i.e., cravings) having closely related cognitive, physiological, subjective, and behavioral dimensions. Processes involved in the development of cravings as a response to adversity are discussed in the context of stress-coping and the construction of embodied rigid appraisals. Thus, embodied IBs are dynamic psychological states emerging from different affective, cognitive, and meta-cognitive processes that activate and maintain embodied simulations of craving and over-reactive incentive salience as ingredients in the context of stress-coping. Psychological interventions based on embodied rigid appraisals are illustrated. At the end of the chapter, a model of embodied rigid appraisals is described.
Social anxiety disorder (SAD) is serious psychiatric condition with a genetic background. Insight into the neurobiological alterations underlying the disorder is essential to develop effective interventions that could relieve SAD-related suffering. In this expert review, we consider recent neuroimaging work on SAD. First, we focus on new results from magnetic resonance imaging studies dedicated to outlining biomarkers of SAD, including encouraging findings with respect to structural and functional brain alterations associated with the disorder. Furthermore, we highlight innovative studies in the field of neuroprediction and studies that established the effects of treatment on brain characteristics. Next, we describe novel work aimed to delineate endophenotypes of SAD, providing insight into the genetic susceptibility to develop the disorder. Finally, we outline outstanding questions and point out directions for future research.
Attending to stimuli that share perceptual similarity to learned threats is an adaptive strategy.However, prolonged threat generalization to cues signalling safety is considered a core feature of pathological anxiety. One potential factor that may sustain over-generalization is sensitivity to future threat uncertainty. To assess the extent to which Intolerance of Uncertainty (IU) predicts threat generalization, we recorded skin conductance in 54 healthy participants during an associative learning paradigm, where threat and safety cues varied in perceptual similarity. Lower IU was associated with stronger discrimination between threat and safety cues during acquisition and extinction. Higher IU, however, was associated with generalized responding to threat andsafety cues during acquisition, and delayed discrimination between threat and safety cues during extinction. These results were specific to IU, over and above other measures of anxious dis-position. These findings highlight: (1) a critical role of uncertainty-based mechanisms in threat generalization, and (2) IU as a potential risk factor for anxiety disorder development.
Significance
The subcortical striatum is critical for the planning and execution of motor behavior, and its dysfunction is associated with disorders such as Parkinson’s disease. More recently, the human striatum has also been reported to be involved in heterogeneous nonmotor psychological functions. However, detailed functional mappings of human psychological processes to striatal regions have been bound by theoretical and methodological limitations, including a strong focus on experimental paradigms derived from animal research, and the tendency to infer function from anatomical connectivity, rather than task-related activation. To overcome these limitations, we used a large-scale, unbiased, data-driven approach, and generated a precise, comprehensive functional map, directly associating striatal zones with the broadest range of psychological processes to date.
Coordination of activity between the amygdala and ventromedial prefrontal cortex (vmPFC) is important for fear-extinction learning. Aberrant recruitment of this circuitry is associated with anxiety disorders. Here, we sought to determine if individual differences in future threat uncertainty sensitivity, a potential risk factor for anxiety disorders, underly compromised recruitment of fear extinction circuitry. Twenty-two healthy subjects completed a cued fear conditioning task with acquisition and extinction phases. During the task, pupil dilation, skin conductance response, and functional magnetic resonance imaging were acquired. We assessed the temporality of fear extinction learning by splitting the extinction phase into early and late extinction. Threat uncertainty sensitivity was measured using self-reported intolerance of uncertainty (IU).
During early extinction learning, we found low IU scores to be associated with larger skin conductance responses and right amygdala activity to learned threat vs. safety cues, whereas high IU scores were associated with no skin conductance discrimination and greater activity within the right amygdala to previously learned safety cues. In late extinction learning, low IU scores were associated with successful inhibition of previously learned threat, reflected in comparable skin conductance response and right amgydala activity to learned threat vs. safety cues, whilst high IU scores were associated with continued fear expression to learned threat, indexed by larger skin conductance and amygdala activity to threat vs. safety cues. In addition, high IU scores were associated with greater vmPFC activity to threat vs. safety cues in late extinction. Similar patterns of IU and extinction learning were found for pupil dilation. The results were specific for IU and did not generalize to self-reported trait anxiety.
Overall, the neural and psychophysiological patterns observed here suggest high IU individuals to disproportionately generalize threat during times of uncertainty, which subsequently compromises fear extinction learning. More broadly, these findings highlight the potential of intolerance of uncertainty-based mechanisms to help understand pathological fear in anxiety disorders and inform potential treatment targets.
Uncertainty about a possible future threat disrupts our ability to avoid it or to mitigate its negative impact and thus results in anxiety. Here, we focus the broad literature on the neurobiology of anxiety through the lens of uncertainty. We identify five processes that are essential for adaptive anticipatory responses to future threat uncertainty and propose that alterations in the neural instantiation of these processes result in maladaptive responses to uncertainty in pathological anxiety. This framework has the potential to advance the classification, diagnosis and treatment of clinical anxiety.
Context Emotion regulation deficits figure prominently in generalized anxiety disorder (GAD) and in other anxiety and mood disorders. Research examining emotion regulation and top-down modulation has implicated reduced coupling of the amygdala with prefrontal cortex and anterior cingulate cortex, suggesting altered frontolimbic white matter connectivity in GAD.
Objectives To investigate structural connectivity between ventral prefrontal cortex or anterior cingulate cortex areas and the amygdala in GAD and to assess associations with functional connectivity between those areas.
Design Participants underwent diffusion-tensor imaging and functional magnetic resonance imaging.
Setting University magnetic resonance imaging facility.
Participants Forty-nine patients with GAD and 39 healthy volunteer control subjects, including a matched subset of 21 patients having GAD without comorbid Axis I diagnoses and 21 healthy volunteers matched for age, sex, and education.
Main Outcome Measures The mean fractional anisotropy values in the left and right uncinate fasciculus, as measured by tract-based analysis for diffusion-tensor imaging data.
Results Lower mean fractional anisotropy values in the bilateral uncinate fasciculus indicated reduced frontolimbic structural connectivity in patients with GAD. This reduction in uncinate fasciculus integrity was most pronounced for patients without comorbidity and was not observed in other white matter tracts. Across all participants, higher fractional anisotropy values were associated with more negative functional coupling between the pregenual anterior cingulate cortex and the amygdala during the anticipation of aversion.
Conclusions Reduced structural connectivity of a major frontolimbic pathway suggests a neural basis for emotion regulation deficits in GAD. The functional significance of these structural differences is underscored by decreased functional connectivity between the anterior cingulate cortex and the amygdala in individuals with reduced structural integrity of the uncinate fasciculus.
Whether obsessive-compulsive disorder (OCD) is adequately classified as an anxiety disorder is a matter of considerable debate.
To quantitatively compare structural brain changes in OCD and other anxiety disorders using novel voxel-based meta-analytical methods and to generate an online database to facilitate replication and further analyses by other researchers.
The PubMed, ScienceDirect, and Scopus databases were searched between 2001 (the date of the first voxel-based morphometry study in any anxiety disorder) and 2009. All voxel-based morphometry studies comparing patients with any anxiety disorder and healthy controls were retrieved. Manual searches were also conducted. Authors were contacted soliciting additional data.
Thirty-seven data sets were identified, of which 26 (including 639 patients with anxiety disorders and 737 healthy controls) met inclusion criteria.
Coordinates were extracted from clusters of significant gray matter difference between patients and controls. Demographic, clinical, and methodological variables were extracted from each study or obtained from the authors.
Patients with anxiety disorders (including OCD) showed decreased bilateral gray matter volumes in the dorsomedial frontal/anterior cingulate gyri. Individuals with OCD had increased bilateral gray matter volumes (vs healthy controls and vs individuals with other anxiety disorders) in the lenticular/caudate nuclei, while patients with other anxiety disorders (mainly panic and posttraumatic stress disorders) had decreased gray matter volumes in the left lenticular nucleus. The findings remained largely unchanged in quartile and jackknife sensitivity analyses. Controlling for potential confounders such as age or antidepressant medication had little impact on the results.
The meta-analysis consistently revealed common as well as distinct neural substrates in OCD and other anxiety disorders. These results have implications for the current debate surrounding the classification of OCD in the DSM-V.
This study investigated neuronal activity in the anterior striatum while monkeys repeatedly learned to associate new instruction stimuli with known behavioral reactions and reinforcers. In a delayed go-nogo task with several trial types, an initial picture instructed the animal to execute or withhold a reaching movement and to expect a liquid reward or not. During learning, new instruction pictures were presented, and animals guessed and performed one of the trial types according to a trial-and-error strategy. Learning of a large number of pictures resulted in a learning set in which learning took place in a few trials and correct performance exceeded 80% in the first 60-90 trials. About 200 task-related striatal neurons studied in both familiar and learning conditions showed three forms of changes during learning. Activations related to the preparation and execution of behavioral reactions and the expectation of reward were maintained in many neurons but occurred in inappropriate trial types when behavioral errors were made. The activations became appropriate for individual trial types when the animals' behavior adapted to the new task contingencies. In particular, reward expectation-related activations occurred initially in both rewarded and unrewarded movement trials and became subsequently restricted to rewarded trials. These changes occurred in parallel with the visible adaptation of reward expectations by the animals. The second learning change consisted in decreases of task-related activations that were either restricted to the initial trials of new learning problems or persisted during the subsequent consolidation phase. They probably reflected reductions in the expectation and preparation of upcoming task events, including reward. The third learning change consisted in transient or sustained increases of activations. These might reflect the increased attention accompanying learning and serve to induce synaptic changes underlying the behavioral adaptations. Both decreases and increases often induced changes in the trial selective occurrence of activations. In conclusion, neurons in anterior striatum showed changes related to adaptations or reductions of expectations in new task situations and displayed activations that might serve to induce structural changes during learning.
This article reviews and interprets neuronal activities related to the expectation and delivery of reward in the primate orbitofrontal cortex, in comparison with slowly discharging neurons in the striatum (caudate, putamen and ventral striatum, including nucleus accumbens) and midbrain dopamine neurons. Orbitofrontal neurons showed three principal forms of reward-related activity during the performance of delayed response tasks, namely responses to reward-predicting instructions, activations during the expectation period immediately preceding reward and responses following reward. These activations discriminated between different rewards, often on the basis of the animals' preferences. Neurons in the striatum were also activated in relation to the expectation and detection of reward but in addition showed activities related to the preparation, initiation and execution of movements which reflected the expected reward. Dopamine neurons responded to rewards and reward-predicting stimuli, and coded an error in the prediction of reward. Thus, the investigated cortical and basal ganglia structures showed multiple, heterogeneous, partly simultaneous activations which were related to specific aspects of rewards. These activations may represent the neuronal substrates of rewards during learning and established behavioral performance. The processing of reward expectations suggests an access to central representations of rewards which may be used for the neuronal control of goaldirected behavior.
Increasing efforts have been made to investigate the underlying pathophysiology of generalized anxiety disorder (GAD), but only limited consistent information is available on gray (GM) and white matter (WM) volume changes in affected adults. Additionally, few studies employed dimensional approaches to GAD pathology. This study compares structural brain imaging data from n=19 GAD subjects and n=24 healthy comparison (HC) subjects, all medication-free and matched on age, sex and education. Separate categorical and dimensional models were employed using voxel-based morphometry for GM and WM. Significantly higher GM volumes were found in GAD subjects mainly in basal ganglia structures and less consistently in the superior temporal pole. For WM, GAD subjects showed significantly lower volumes in the dlPFC. Largely consistent findings in dimensional and categorical models point toward these structural alterations being reliable and of importance for GAD. While lower volume in the dlPFC could reflect impaired emotional processing and control over worry in GAD, basal ganglia alterations may be linked to disturbed gain and loss anticipation as implicated in previous functional GAD studies. As perturbations in anticipation processes are central to GAD, these areas may warrant greater attention in future studies.
Background:
Experimental extinction serves as a model for psychiatric treatments based on associative learning. However, the effects of extinction are often transient, as evidenced by postextinction return of defensive behaviors. From a therapeutic perspective, an inherent problem with extinction may be that mere omission of threat is not sufficient to reduce future threat uncertainty. The current study tested an augmented form of extinction that replaced, rather than merely omitted, expected threat outcomes with novel nonthreat outcomes, with the goal of reducing postextinction return of defensive behaviors.
Methods:
Thirty-two healthy male Sprague-Dawley rats and 47 human adults underwent threat conditioning to a conditioned stimulus paired with an electrical shock. Subjects then underwent a standard extinction protocol with shock omitted or an augmented extinction protocol wherein the shock was replaced by a surprising tone. Tests of postextinction recovery occurred 24 hours later in the absence of the tone.
Results:
Replacing the shock with a novel nonthreat outcome, as compared with shock omission, reduced postextinction recovery (freezing in rats and anticipatory skin conductance responses in humans) when tested 24 hours later. Self-reported intolerance of uncertainty was positively correlated with recovery following standard extinction in humans, providing new evidence that postextinction recovery is related to sensitivity to future threat uncertainty.
Conclusions:
These findings provide cross-species evidence of a novel strategy to enhance extinction that may have broad implications for how to override associative learning that has become maladaptive and offer a simple technique that could be straightforwardly adapted and implemented in clinical situations.
This review presents an overview of studies investigating white-matter integrity in patients with obsessive-compulsive disorder (OCD) using diffusion tensor imaging (DTI). There is increasing evidence for white matter alterations in OCD. In adult patients the majority of all studies reported abnormalities in terms of decreased fractional anisotropy (FA) compared to healthy volunteers. Although findings are heterogeneous, the cingulate bundle, the corpus callosum and the anterior limb of the internal capsule are most commonly affected by decreased white matter integrity in adult OCD patients. In pediatric and adolescent patients initial evidence points more towards increased white matter connectivity. Thus, current results suggest alterations in various white matter regions in both pediatric and adult OCD patients. They indicate that alterations may vary as a function of clinical characteristics and may be amenable to pharmacologic treatment. Although the findings have important implications for the neurobiology of OCD they also raise a number of important questions that are discussed in this review and need to be taken into consideration in future studies.
1. Residuals from linear regressions are used frequently in statistical analysis, often for the purpose of controlling for unwanted effects in multivariable datasets. This paper criticizes the practice, building upon recent critiques. 2. Regression of residuals is often used as an alternative to multiple regression, often with the aim of controlling for confounding variables. When correlations exist between independent variables, as is generally the case with ecological datasets, this procedure leads to biased parameter estimates. Standard multiple regression, by contrast, yields unbiased parameter estimates. 3. In multiple regression parameters are estimated controlling for the effects of the other variables in the model, and thus multiple regression achieves what residual regression claims to do. 4. Several measures of correlation exist that differ in the way that variance is partitioned among independent variables. These can be estimated multiply, or sequentially if reasons exist for estimating effects of variables in a hierarchical manner.
Voxel-based-morphometry (VBM) is a whole-brain, unbiased technique for characterizing regional cerebral volume and tissue concentration differences in structural magnetic resonance images. We describe an optimized method of VBM to examine the effects of age on grey and white matter and CSF in 465 normal adults. Global grey matter volume decreased linearly with age, with a significantly steeper decline in males. Local areas of accelerated loss were observed bilaterally in the insula, superior parietal gyri, central sulci, and cingulate sulci. Areas exhibiting little or no age effect (relative preservation) were noted in the amygdala, hippocampi, and entorhinal cortex. Global white matter did not decline with age, but local areas of relative accelerated loss and preservation were seen. There was no interaction of age with sex for regionally specific effects. These results corroborate previous reports and indicate that VBM is a useful technique for studying structural brain correlates of ageing through life in humans.
The psychology of extinction has been studied for decades. Approximately 10 years ago, however, there began a concerted effort to understand the neural circuits of extinction of fear conditioning, in both animals and humans. Progress during this period has been facilitated by a high degree of coordination between rodent and human researchers examining fear extinction. Here we review the major advances and highlight new approaches to understanding and exploiting fear extinction. Research in fear extinction could serve as a model for translational research in other areas of behavioral neuroscience.
The dynamic interactions between the amygdala and the medial prefrontal cortex (mPFC) are usefully conceptualized as a circuit that both allows us to react automatically to biologically relevant predictive stimuli as well as regulate these reactions when the situation calls for it. In this review, we will begin by discussing the role of this amygdala-mPFC circuitry in the conditioning and extinction of aversive learning in animals. We will then relate these data to emotional regulation paradigms in humans. Finally, we will consider how these processes are compromised in normal and pathological anxiety. We conclude that the capacity for efficient crosstalk between the amygdala and the mPFC, which is represented as the strength of the amygdala-mPFC circuitry, is crucial to beneficial outcomes in terms of reported anxiety.
A package of computer programs for analysis and visualization of three-dimensional human brain functional magnetic resonance imaging (FMRI) results is described. The software can color overlay neural activation maps onto higher resolution anatomical scans. Slices in each cardinal plane can be viewed simultaneously. Manual placement of markers on anatomical landmarks allows transformation of anatomical and functional scans into stereotaxic (Talairach-Tournoux) coordinates. The techniques for automatically generating transformed functional data sets from manually labeled anatomical data sets are described. Facilities are provided for several types of statistical analyses of multiple 3D functional data sets. The programs are written in ANSI C and Motif 1.2 to run on Unix workstations.
The field of neuroscience has, after a long period of looking the other way, again embraced emotion as an important research area. Much of the progress has come from studies of fear, and especially fear conditioning. This work has pinpointed the amygdala as an important component of the system involved in the acquisition, storage, and expression of fear memory and has elucidated in detail how stimuli enter, travel through, and exit the amygdala. Some progress has also been made in understanding the cellular and molecular mechanisms that underlie fear conditioning, and recent studies have also shown that the findings from experimental animals apply to the human brain. It is important to remember why this work on emotion succeeded where past efforts failed. It focused on a psychologically well-defined aspect of emotion, avoided vague and poorly defined concepts such as "affect," "hedonic tone," or "emotional feelings," and used a simple and straightforward experimental approach. With so much research being done in this area today, it is important that the mistakes of the past not be made again. It is also time to expand from this foundation into broader aspects of mind and behavior.
An anatomical parcellation of the spatially normalized single-subject high-resolution T1 volume provided by the Montreal Neurological Institute (MNI) (D. L. Collins et al., 1998, Trans. Med. Imag. 17, 463-468) was performed. The MNI single-subject main sulci were first delineated and further used as landmarks for the 3D definition of 45 anatomical volumes of interest (AVOI) in each hemisphere. This procedure was performed using a dedicated software which allowed a 3D following of the sulci course on the edited brain. Regions of interest were then drawn manually with the same software every 2 mm on the axial slices of the high-resolution MNI single subject. The 90 AVOI were reconstructed and assigned a label. Using this parcellation method, three procedures to perform the automated anatomical labeling of functional studies are proposed: (1) labeling of an extremum defined by a set of coordinates, (2) percentage of voxels belonging to each of the AVOI intersected by a sphere centered by a set of coordinates, and (3) percentage of voxels belonging to each of the AVOI intersected by an activated cluster. An interface with the Statistical Parametric Mapping package (SPM, J. Ashburner and K. J. Friston, 1999, Hum. Brain Mapp. 7, 254-266) is provided as a freeware to researchers of the neuroimaging community. We believe that this tool is an improvement for the macroscopical labeling of activated area compared to labeling assessed using the Talairach atlas brain in which deformations are well known. However, this tool does not alleviate the need for more sophisticated labeling strategies based on anatomical or cytoarchitectonic probabilistic maps.
Research is now suggesting that intolerance of uncertainty may be very important in understanding worry and may play a key role in the etiology and maintenance of worry. The present study attempted to further our understanding of intolerance of uncertainty by examining the psychometric properties of the English version of the Intolerance of Uncertainty Scale (IUS), which has already been validated in French. Factor analysis indicated that the IUS has a four-factor structure that represents the idea that uncertainty is stressful and upsetting, uncertainty leads to the inability to act, uncertain events are negative and should be avoided, and being uncertain is unfair. The IUS has excellent internal consistency, good test-retest reliability over a five-week period, and convergent and divergent validity when assessed with symptom measures of worry, depression, and anxiety. Overall, this study suggests that the IUS is a sound measure of intolerance of uncertainty and supports the idea that intolerance of uncertainty is an important construct involved in worry.
Linear registration and motion correction are important components of structural and functional brain image analysis. Most modern methods optimize some intensity-based cost function to determine the best registration. To date, little attention has been focused on the optimization method itself, even though the success of most registration methods hinges on the quality of this optimization. This paper examines the optimization process in detail and demonstrates that the commonly used multiresolution local optimization methods can, and do, get trapped in local minima. To address this problem, two approaches are taken: (1) to apodize the cost function and (2) to employ a novel hybrid global-local optimization method. This new optimization method is specifically designed for registering whole brain images. It substantially reduces the likelihood of producing misregistrations due to being trapped by local minima. The increased robustness of the method, compared to other commonly used methods, is demonstrated by a consistency test. In addition, the accuracy of the registration is demonstrated by a series of experiments with motion correction. These motion correction experiments also investigate how the results are affected by different cost functions and interpolation methods.
A fully probabilistic framework is presented for estimating local probability density functions on parameters of interest in a model of diffusion. This technique is applied to the estimation of parameters in the diffusion tensor model, and also to a simple partial volume model of diffusion. In both cases the parameters of interest include parameters defining local fiber direction. A technique is then presented for using these density functions to estimate global connectivity (i.e., the probability of the existence of a connection through the data field, between any two distant points), allowing for the quantification of belief in tractography results. This technique is then applied to the estimation of the cortical connectivity of the human thalamus. The resulting connectivity distributions correspond well with predictions from invasive tracer methods in nonhuman primate.
In the treatment of anxious youth, children's symptom presentations cannot always be readily distinguished as indicative of obsessive-compulsive disorder (OCD) or generalized anxiety disorder (GAD). Following a definition and brief description of the phenomenology, epidemiology, and treatment of OCD and GAD in youth, consideration is given to factors that contribute to the proximity of the two disorders. In an effort to better understand the distinctive and overlapping features of these neighboring disorders, we review (a) obsessions and worry, with reference to process, form, content, and metacognitive beliefs, and (b) the literature on pathological worry and covert compulsions. Studies from the adult literature are considered throughout, and the absence of related work with samples of youth, within a developmental framework, is highlighted. Suggestions for future research are offered.
The techniques available for the interrogation and analysis of neuroimaging data have a large influence in determining the flexibility, sensitivity, and scope of neuroimaging experiments. The development of such methodologies has allowed investigators to address scientific questions that could not previously be answered and, as such, has become an important research area in its own right. In this paper, we present a review of the research carried out by the Analysis Group at the Oxford Centre for Functional MRI of the Brain (FMRIB). This research has focussed on the development of new methodologies for the analysis of both structural and functional magnetic resonance imaging data. The majority of the research laid out in this paper has been implemented as freely available software tools within FMRIB's Software Library (FSL).
There has been much recent interest in using magnetic resonance diffusion imaging to provide information about anatomical connectivity in the brain, by measuring the anisotropic diffusion of water in white matter tracts. One of the measures most commonly derived from diffusion data is fractional anisotropy (FA), which quantifies how strongly directional the local tract structure is. Many imaging studies are starting to use FA images in voxelwise statistical analyses, in order to localise brain changes related to development, degeneration and disease. However, optimal analysis is compromised by the use of standard registration algorithms; there has not to date been a satisfactory solution to the question of how to align FA images from multiple subjects in a way that allows for valid conclusions to be drawn from the subsequent voxelwise analysis. Furthermore, the arbitrariness of the choice of spatial smoothing extent has not yet been resolved. In this paper, we present a new method that aims to solve these issues via (a) carefully tuned non-linear registration, followed by (b) projection onto an alignment-invariant tract representation (the "mean FA skeleton"). We refer to this new approach as Tract-Based Spatial Statistics (TBSS). TBSS aims to improve the sensitivity, objectivity and interpretability of analysis of multi-subject diffusion imaging studies. We describe TBSS in detail and present example TBSS results from several diffusion imaging studies.
The dimensionality and correlates of the Intolerance of Uncertainty Scale (IUS) were examined in a sample of 239 university students. In addition to completing the IUS, participants completed measures of worrying, anxious arousal, anhedonic depression, the big five personality dimensions, and the Need for Closure Scale. A factor analysis of the IUS suggested that it includes the following dimensions: (a) desire for predictability; (b) tendency to become paralyzed in the face of uncertainty; (c) tendency to experience distress in the face of uncertainty; and (d) inflexible uncertainty beliefs. Subscale scores computed on the basis of the factor analysis were differentially associated with the other variables.
Intolerance of uncertainty (IU), or the increased affective response to situations with uncertain outcomes, is an important component process of anxiety disorders. Increased IU is observed in panic disorder (PD), obsessive compulsive disorder (OCD) and generalized anxiety disorder (GAD), and is thought to relate to dysfunctional behaviors and thought patterns in these disorders. Identifying what brain systems are associated with IU would contribute to a comprehensive model of anxiety processing, and increase our understanding of the neurobiology of anxiety disorders. Here, we used a behavioral task, Wall of Faces (WOFs), during functional magnetic resonance imaging (fMRI), which probes both affect and ambiguity, to examine the neural circuitry of IU in 14 (10 females) college age (18.8 years) subjects. All subjects completed the Intolerance of Uncertainty Scale (IUS), Anxiety Sensitivity Index (ASI), and a measure of neuroticism (i.e. the NEO-N). IUS scores but neither ASI nor NEO-N scores, correlated positively with activation in bilateral insula during affective ambiguity. Thus, the experience of IU during certain types of emotion processing may relate to the degree to which bilateral insula processes uncertainty. Previously observed insula hyperactivity in anxiety disorder individuals may therefore be directly linked to altered processes of uncertainty.
Linear registration and motion correction are important components of structural and functional brain image analysis. Most modern methods optimise some intensity-based cost function to determine the best registration.