# Brain Imaging and Behavior

Online ISSN: 1931-7565
Recent publications
Article
Type 2 diabetes mellitus (T2DM) is associated with brain damage and cognitive decline. Despite the fact that the thalamus involves aspects of cognition and is typically affected in T2DM, existing knowledge of subregion-level thalamic damage and its associations with cognitive performance in T2DM patients is limited. The thalamus was subdivided into 8 subregions in each hemisphere. Resting-state functional and structural MRI data were collected to calculate resting-state functional connectivity (rsFC) and gray matter volume (GMV) of each thalamic subregion in 62 T2DM patients and 50 healthy controls. Compared with controls, T2DM patients showed increased rsFC of the medial pre-frontal thalamus, posterior parietal thalamus, and occipital thalamus with multiple cortical regions. Moreover, these thalamic functional hyperconnectivity were associated with better cognitive performance and lower glucose variability in T2DM patients. However, there were no group differences in GMV for any thalamic subregions. These findings suggest a possible neural compensation mechanism whereby selective thalamocortical functional hyperconnectivity facilitated by better glycemic control help to preserve cognitive ability in T2DM patients, which may ultimately inform intervention and prevention of T2DM-related cognitive decline in real-world clinical settings.

Article
Computational imaging and quantitative biomarkers offer invaluable insights in the pre-symptomatic phase of neurodegenerative conditions several years before clinical manifestation. In recent years, there has been a focused effort to characterize pre-symptomatic cerebral changes in familial frontotemporal dementias using computational imaging. Accordingly, a systematic literature review was conducted of original articles investigating pre-symptomatic imaging changes in frontotemporal dementia focusing on study design, imaging modalities, data interpretation, control cohorts and key findings. The review is limited to the most common genotypes: chromosome 9 open reading frame 72 ( C9orf72 ), progranulin ( GRN ), or microtubule-associated protein tau ( MAPT ) genotypes. Sixty-eight studies were identified with a median sample size of 15 (3–141) per genotype. Only a minority of studies were longitudinal (28%; 19/68) with a median follow-up of 2 (1–8) years. MRI (97%; 66/68) was the most common imaging modality, and primarily grey matter analyses were conducted (75%; 19/68). Some studies used multimodal analyses 44% (30/68). Genotype-associated imaging signatures are presented, innovative study designs are highlighted, common methodological shortcomings are discussed and lessons for future studies are outlined. Emerging academic observations have potential clinical implications for expediting the diagnosis, tracking disease progression and optimising the timing of pharmaceutical trials.

Article
Non-small cell lung cancer (NSCLC) accounts for more than 85% of all lung cancer cases, and chemotherapy-related brain changes (known as “chemobrain”) in NSCLC patients were found in previous studies. However, the effects of platinum-based chemotherapy on brain structural networks are still unclear. Structural magnetic resonance imaging (sMRI) data were collected from 32 NSCLC patients following platinum-based chemotherapy, 36 NSCLC patients without chemotherapy, and 39 healthy controls. Clinical physiological indicators of patients were collected. Then, morphological similarity networks were constructed using MRI data, and topological properties were calculated using graph theory method. Differences between three groups were investigated using one-way ANOVA and two-sample t-test, and relations between topological properties and clinical physiological indicators were calculated. We found that degree and nodal efficiency in temporal-parietal networks were significantly reduced in NSCLC patients following platinum-based chemotherapy compared to healthy controls/patients without chemotherapy (F-test, p < 0.001; post hoc t-test, p < 0.01, Bonferroni corrected). These changes (p < 0.05) were positively correlated with clinical measures, including thrombocytes, granulocytes and hemoglobin, and were negatively correlated with measures of triglycerides and cholesterol levels. Network properties including clustering coefficient (F(2,104) = 41.435, p < 0.001), number of K-edges (F(2,104) = 40.304, p < 0.001), density of K-edges (F(2,104) = 40.304, p < 0.001), global efficiency (F(2,104) = 42.585, p < 0.001) and small-world (F(2,104) = 37.132, p < 0.001) were also significantly reduced (post hoc t-test, p < 0.01, Bonferroni corrected). These results indicate that platinum-based chemotherapy might cause cerebrovascular damage and clinical indicators’ changes, which then cause the properties of morphological similarity networks’ changes in the temporal and parietal lobes. This study may help us better understand the “chemobrain” in NSCLC patients.

Article
Mindfulness training has been associated with improved attention and affect regulation in preadolescent children with anxiety related attention impairments, however little is known about the underlying neurobiology. This study sought to investigate the impact of mindfulness training on functional connectivity of attention and limbic brain networks in pre-adolescents. A total of 47 children with anxiety and/or attention issues (aged 9-11 years) participated in a 10-week mindfulness intervention. Anxiety and attention measures and resting-state fMRI were completed at pre- and post-intervention. Sustained attention was measured using the Conners Continuous Performance Test, while the anxiety levels were measured using the Spence Children’s Anxiety Scale. Functional networks were estimated using independent-component analysis, and voxel-based analysis was used to determine the difference between the time-points to identify the effect of the intervention on the functional connectivity. There was a significant decrease in anxiety symptoms and improvement in attention scores following the intervention. From a network perspective, the results showed increased functional connectivity post intervention in the salience and fronto-parietal networks as well as the medial-inferior temporal component of the default mode network. Positive correlations were identified in the fronto-parietal network with Hit Response Time and the Spence Children’s Anxiety Scale total and between the default mode network and Hit Response Time. A 10-week mindfulness intervention in children was associated with a reduction in anxiety related attention impairments, which corresponded with concomitant changes in functional connectivity.

Article
Individuals with schizophrenia have higher rates of suicide attempts than the general population. Specific cortical abnormalities (e.g., the cortical surface area and thickness) may be associated with a history of suicide attempts. We recruited 74 individuals with schizophrenia (37 suicide attempters were individually matched with 37 non-attempters on age, sex, phase of illness, and study center) and 37 healthy volunteers. The cortical surface area and thickness data were extracted from structural MRI and compared between the groups. Suicide attempters showed significantly smaller surface areas in the whole brain (p = .028, Cohen’s d = -0.54) than non-attempters. No association was found between the cortical surface area of individual brain regions and a history of suicide attempts. The mean cortical thickness did not differ significantly between the groups; however, suicide attempters demonstrated a thinner cortex in the right superior temporal gyrus (p < .001, q = 0.037, Cohen’s d = -0.88). These findings indicate that a history of suicide attempts among individuals with schizophrenia is associated with a reduction in the global cortical surface area and specific cortical thinning of the right superior temporal gyrus. The morphometric alteration of the right superior temporal gyrus may represent a biomarker of suicidal behavior in individuals with schizophrenia.

Article
This study aimed to investigate the alterations of cognition and functional connectivity post noise, and find the progress and neural substrates of noise induced hearing loss (NIHL)-associated cognitive impairment. We exposed rats to 122 dB broad-band noise for 2 h to induce hearing loss and the auditory function was assessed by measuring auditory brainstem response thresholds. Morris water maze test and resting state MRI were computed at 0 day, 1, 3, 6 months post noise to reveal cognitive ability and neural substrate. The interregional connections in the auditory network and default mode network, as well as the connections using the auditory cortex and cingulate cortex as seeds were also examined addtionally. The deficit in spatial learning/memory was only observed at 6 months after noise exposure. The internal connections in the auditory network and default mode network were enhanced at 0 day and decreased at 6 months post noise. The connectivity using the auditory cortex and cingulate cortex as seeds generally followed the rule of “enhancement-normal-decrease-widely decrease”. A new model accounting for arousal, dementia, motor control of NIHL in is proposed. Our study highlights the fundamental flexibility of neural systems, and may also point toward novel therapeutic strategies for treating sensory disorders.

Article
Neuroimaging studies have identified alterations in functional connectivity between specific brain regions in patients with unilateral hearing loss (UHL) and different influence of the side of UHL on neural plasticity. However, little is known about changes of whole-brain functional networks in patients with UHL and whether differences exist in topological organization between right-sided UHL (RUHL) and left-sided UHL (LUHL). To address this issue, we employed resting-state fMRI (rs-fMRI) and graph-theoretical approaches to investigate the topological alterations of brain functional connectomes in patients with RUHL and LUHL. Data from 44 patients with UHL (including 22 RUHL patients and 22 LUHL patients) and 37 healthy control subjects (HCs) were collected. Functional brain networks were constructed for each participant, following by graph-theoretical network analyses at connectional and global (e.g., small-worldness) levels. The correlations between brain network topologies and clinical variables were further studied. Using network-based analysis, we found a subnetwork in the visual cortex which had significantly lower connectivity strength in patients with RUHL as compared to HCs. At global level, all participants showed small-world architecture in functional brain networks, however, significantly lower normalized clustering coefficient and small-worldness were observed in patients with RUHL than in HCs. Moreover, these abnormal network metrics were demonstrated to be correlated with the clinical variables and cognitive performance of patients with RUHL. Notably, no significant alterations in the functional brain networks were found in patients with LUHL. Our findings demonstrate that RUHL (rather than LUHL) is accompanied with aberrant topological organization of the functional brain connectome, indicating different pathophysiological mechanisms between RUHL and LUHL from a viewpoint of network topology.

Article
Older age is associated with worsened outcome after mild traumatic brain injury (mTBI) and a higher risk of developing persistent post-traumatic complaints. However, the effects of mTBI sequelae on brain connectivity at older age and their association with post-traumatic complaints remain understudied. We analyzed multi-echo resting-state functional magnetic resonance imaging data from 25 older adults with mTBI (mean age: 68 years, SD: 5 years) in the subacute phase (mean injury to scan interval: 38 days, SD: 9 days) and 20 age-matched controls. Severity of complaints (e.g. fatigue, dizziness) was assessed using self-reported questionnaires. Group independent component analysis was used to identify intrinsic connectivity networks (ICNs). The effects of group and severity of complaints on ICNs were assessed using spatial maps intensity (SMI) as a measure of within-network connectivity, and (static) functional network connectivity (FNC) as a measure of between-network connectivity. Patients indicated a higher total severity of complaints than controls. Regarding SMI measures, we observed hyperconnectivity in left-mid temporal gyrus (cognitive-language network) and hypoconnectivity in the right-fusiform gyrus (visual-cerebellar network) that were associated with group. Additionally, we found interaction effects for SMI between severity of complaints and group in the visual(-cerebellar) domain. Regarding FNC measures, no significant effects were found. In older adults, changes in cognitive-language and visual(-cerebellar) networks are related to mTBI. Additionally, group-dependent associations between connectivity within visual(-cerebellar) networks and severity of complaints might indicate post-injury (mal)adaptive mechanisms, which could partly explain post-traumatic complaints (such as dizziness and balance disorders) that are common in older adults during the subacute phase.

Article
Accumulating evidence suggests the critical role of cortical thinning in the pathophysiology of major depressive disorder. However, the association of cortical thickness and cognitive impairment with treatment-resistant depression (TRD) has rarely been investigated. In total, 48 adult patients with TRD and 48 healthy controls were recruited and administered a series of neurocognitive and neuroimaging examinations, including 1-back and 2-back working memory tasks and brain magnetic resonance imaging (MRI). Whole-brain cortical thickness analysis was performed to investigate the differences in the cortical thickness between patients with TRD and controls. The patients had reduced cortical thickness in the frontal cortex, particularly at the left frontal pole, left inferior frontal cortex, and left anterior cingulate cortex, and left middle temporal cortex compared with the healthy controls. Moreover, in the 2-back working memory task, the cortical thickness in the left frontal pole and left anterior cingulate cortex was positively associated with mean error in the patients, but not in the controls. Reduced cortical thickness in the frontal pole and anterior cingulate cortex is associated with TRD and related cognitive impairment. Our study indicated the crucial effects of the frontal and temporal cortical thickness on the pathophysiology of TRD and cognitive impairment in patients with TRD.

Article
CSF1R-related leukoencephalopathy is an adult-onset white matter disease with high disability and mortality, while little is known about its pathogenesis. This study introduced amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) based on resting-state functional magnetic resonance imaging(rsfMRI) to compare the spontaneous brain activities of patients and healthy controls, aiming to enhance our understanding of the disease. RsfMRI was performed on 16 patients and 23 healthy controls, and preprocessed for calculation of ALFF and ReHo. Permutation tests with threshold free cluster enhancement (TFCE) was applied for comparison (number of permutations = 5,000). The TFCE significance threshold was set at PFWE\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${P}_{FWE}$$\end{document} < 0.05. In addition, 10 was set as the minimum cluster size. Compared to healthy controls, the patient group showed decreased ALFF in right paracentral lobule, and increased ALFF in bilateral insula, hippocampus, thalamus, supramarginal and precentral gyrus, right inferior, middle and superior frontal gyrus, right superior and middle occipital gyrus, as well as left parahippocampal gyrus, fusiform, middle occipital gyrus and angular gyrus. ReHo was decreased in right supplementary motor area, paracentral lobule and precentral gyrus, while increased in right superior occipital gyrus and supramarginal gyrus, left parahippocampal gyrus, hippocampus, fusiform, middle occipital gyrus and angular gyrus, as well as bilateral middle occipital gyrus and midbrain. These results revealed altered spontaneous brain activities in CSF1R-related leukoencephalopathy, especially in limbic system and motor cortex, which may shed light on underlying mechanisms.

Article
Previous neuroimaging studies have demonstrated that sleep is associated with brain functional changes in some specific brain regions. However, few studies have examined the relationship between all possible functional connectivities (FCs) within the sensory/somatomotor network (SSN) and the sleep quality of young male samples. The SSN consists of two motor cortices and is known to play a critical role in sleep. Poor sleep quality may be associated with increased sensory/somatomotor functional connectivity during rest. Hence, 202 young male participants underwent a resting-state functional magnetic resonance imaging (fMRI) scan and completed the Pittsburgh Sleep Quality Index (PSQI). Results indicated that increased functional connectivity within the SSN was associated with poor sleep quality. Specifically, the total PSQI score was positively correlated with the increased functional connectivity of the left paracentral lobule (PCL), bilateral precentral gyrus (PreCG), supplementary motor area (SMA) and bilateral postcentral gyrus (PoCG). Additionally, our findings also exhibited that (a) the subjective sleep quality factor of PSQI was positively correlated with FC between the bilateral PoCG and the bilateral PCL as well as between the left PreCG and the right SMA; (b) the sleep latency factor of PSQI was positively correlated with FC between the left PoCG and the right precuneus (PCUN); (c) the sleep disturbances factor of PSQI was positively correlated with FC between the left PCL and the right PoCG, and (d) the daytime dysfunction factor of PSQI was positively correlated with FC between the bilateral PoCG and the left PCL as well as between the bilateral PreCG and the SMA. In short, our findings can be comprehensively understood as neural mechanisms of intrinsic SSN connectivity are associated with sleep quality of man. Meanwhile, it may expand our knowledge and provide new insight into a deeper understanding of the neurobiological mechanisms of sleep or sleep problems.

Article
Post-stroke neuroplasticity and cognitive recovery can be enhanced by multimodal stimulation via environmental enrichment. In this vein, recent studies have shown that enriched sound environment (i.e., listening to music) during the subacute post-stroke stage improves cognitive outcomes compared to standard care. The beneficial effects of post-stroke music listening are further pronounced when listening to music containing singing, which enhances language recovery coupled with structural and functional connectivity changes within the language network. However, outside the language network, virtually nothing is known about the effects of enriched sound environment on the structural connectome of the recovering post-stroke brain. Here, we report secondary outcomes from a single-blind randomized controlled trial (NCT01749709) in patients with ischaemic or haemorrhagic stroke (N = 38) who were randomly assigned to listen to vocal music, instrumental music, or audiobooks during the first 3 post-stroke months. Utilizing the longitudinal diffusion-weighted MRI data of the trial, the present study aimed to determine whether the music listening interventions induce changes on structural white matter connectome compared to the control audiobook intervention. Both vocal and instrumental music groups increased quantitative anisotropy longitudinally in multiple left dorsal and ventral tracts as well as in the corpus callosum, and also in the right hemisphere compared to the audiobook group. Audiobook group did not show increased structural connectivity changes compared to both vocal and instrumental music groups. This study shows that listening to music, either vocal or instrumental promotes wide-spread structural connectivity changes in the post-stroke brain, providing a fertile ground for functional restoration.

Article
Subject-level independent component analysis (ICA) is a well-established and widely used approach in denoising of resting-state functional magnetic resonance imaging (fMRI) data. However, approaches such as ICA-FIX and ICA-AROMA require advanced setups and can be computationally intensive. Here, we aim to introduce a user-friendly, computationally lightweight toolbox for labeling independent signal and noise components, termed Alternative Labeling Tool (ALT). ALT uses two features that require manual tuning: proportion of an independent component’s spatial map located inside gray matter and positive skew of the power spectrum. ALT is tightly integrated with the commonly used FMRIB’s statistical library (FSL). Using the Open Access Series of Imaging Studies (OASIS-3) ageing dataset (n = 275), we found that ALT shows a high degree of inter-rater agreement with manual labeling (over 86% of true positives for both signal and noise components on average). In conclusion, ALT can be extended to small and large-scale datasets when the use of more complex tools such as ICA-FIX is not possible. ALT will thus allow for more widespread adoption of ICA-based denoising of resting-state fMRI data.

Article
Previous studies have reported changes in white matter microstructures in patients with insomnia. However, few neuroimaging studies have focused specifically on white matter tracts in insomnia patients after having received treatment. In this prospective study, diffusion-tensor imaging was used in two samples of heart-kidney imbalance insomnia patients who were treated with placebo or Jiao-Tai-Wan, a traditional Chinese medicine commonly used to treat heart-kidney imbalance insomnia, to assess the changes in white matter tracts. Tract-based spatial statistical analyses were first applied to compare the changes in mean diffusivity and fractional anisotropy of white matter between 75 heart-kidney imbalance insomnia patients and 41 healthy control participants. In subsequent randomized, double-blind, placebo-controlled trials, comparisons of mean diffusivity and fractional anisotropy were also performed in 24 heart-kidney imbalance insomnia patients (8 males; 16 females; 42.5 ± 10.4 years) with Jiao-Tai-Wan and 26 heart-kidney imbalance insomnia patients (11 males; 15 females; 39.7 ± 9.4 years) with a placebo, with age and sex as covariates. Fractional anisotropy values in left corticospinal tract were increased in heart-kidney imbalance insomnia patients. Heart-kidney imbalance insomnia patients showed lower mean diffusivity and fractional anisotropy values of several white matter tracts than healthy control participants, such as the bilateral anterior limb of internal capsule, bilateral superior longitudinal fasciculus and bilateral posterior corona radiata. After being treated with Jiao-Tai-Wan, heart-kidney imbalance insomnia patients showed a trend towards reduced fractional anisotropy values in the left corticospinal tract. Jiao-Tai-Wan may improve the sleep quality by reversing the structural changes of the left corticospinal tract caused by heart-kidney imbalance insomnia.

Article
Patients with neuropathic pain and fibromyalgia showed reduced or absent offset analgesia (OA) response and attenuated cerebral activity in descending pain modulatory and reward systems in patients. However, neural network modifications of OA in chronic pain have not been determined. We enrolled 23 patients with various chronic pain and 17 age- and gender- matched healthy controls. All participants were given OA-related noxious thermal stimuli, including 3 repeats of offset analgesia paradigm at 46–47-46 °C and constant paradigm at 46 °C on the left volar forearm under whole-brain functional magnitude resonance imaging (fMRI). We evaluated magnitude of OA, examined OA modulated functional connectivity using psychophysiological interaction analysis and resting-state functional connectivity analysis and explored their behavioral correlations in patients compared with controls. Compared to controls, chronic pain patients showed smaller magnitude of OA (P = 0.047). OA modulated connectivity decreased between posterior cingulate cortex (PCC) and right medial prefrontal cortex (MPFC) in proportion to current chronic pain (P = 0.018); decreased between right pallidum and right thalamus, and increased between right caudate nucleus and left primary somatosensory cortex (PFDR < 0.05). The impaired PCC-MPFC connectivity might play an important role in dysfunction of OA and contribute to pain chronification.

Article
Expression of executive dysfunctions is marked by substantial heterogeneity in people living with HIV infection (PLWH) and attributed to neuropathological degradation of frontostriatal circuitry with age and disease. We compared the neurophysiology of executive function in older PLWH and Parkinson’s disease (PD), both affecting frontostriatal systems. Thirty-one older PLWH, 35 individuals with PD, and 28 older healthy controls underwent executive task-activated fMRI, neuropsychological testing, and a clinical motor exam. fMRI task conditions distinguished cognitive control operations, invoking a lateral frontoparietal network, and motor control operations, activating a cerebellar-precentral-medial prefrontal network. HIV-specific findings denoted a prominent sensorimotor hypoactivation during cognitive control and striatal hypoactivation during motor control related to CD4⁺ T cell count and HIV disease duration. Activation deficits overlapped for PLWH and PD, relative to controls, in dorsolateral frontal, medial frontal, and middle cingulate cortices for cognitive control, and in limbic, frontal, parietal, and cerebellar regions for motor control. Thus, despite well-controlled HIV infection, frontostriatal and sensorimotor activation deficits occurred during executive control in older PLWH. Overlapping activation deficits in posterior cingulate and hippocampal regions point toward similarities in mesocorticolimbic system aberrations among older PLWH and PD. The extent of pathophysiology in PLWH was associated with variations in immune system health, neural signature consistent with subclinical parkinsonism, and mild neurocognitive impairment. The failure to adequately engage these pathways could be an early sign for cognitive and motor functional decline in the aging population of PLWH.

Article
An association has been shown between chronic cigarette smoking and structural abnormalities in the brain areas related to several functions relevant to addictive behavior. However, few studies have focused on the structural alternations of chronic smoking by using magnetic resonance imaging (MRI). Also, it remains unclear how structural alternations are associated with tobacco-dependence severity and the positive/negative outcome expectances. The q-sampling imaging (GQI) is an advanced diffusion MRI technique that can reconstruct more precise and consistent images of complex oriented fibers than other methods. We aimed to use GQI to evaluate the impact of the neurological structure caused by chronic smoking. Sixty-seven chronic smokers and 43 nonsmokers underwent a MRI scan. The tobacco dependence severity and the positive/negative outcome expectancies were assessed via self-report. We used GQI with voxel-based statistical analysis (VBA) to evaluate structural brain and connectivity abnormalities. Graph theoretical analysis (GTA) and network-based statistical (NBS) analysis were also performed to identify the structural network differences among groups. Chronic smokers had smaller GM and WM volumes in the bilateral frontal lobe and bilateral frontal region. The GM/WM volumes correlated with dependence severity and outcome expectancies in the brain areas involving high-level functions. Chronic smokers had shape changes in the left hippocampal head and tail and the inferior brain stem. Poorer WM integrity in chronic smokers was found in the left middle frontal region, the right superior fronto-occipital fasciculus, the right temporal region, the left parahippocampus, the left anterior internal capsule, and the right inferior parietal region. WM integrity correlated with dependence severity and outcome expectancies in brain areas involving high-level functions. Chronic smokers had decreased local segregation and global integration among the brain regions and networks. Our results provide further evidence indicating that chronic smoking may be associated with brain structure and connectivity changes.

Article
The diagnostic performance of a combined architecture on Parkinson’s disease using diffusion tensor imaging was evaluated. A convolutional neural network was trained from multiple parcellated brain regions. A greedy algorithm was proposed to combine the models from individual regions into a complex one. Total 305 Parkinson’s disease patients (aged 59.9±9.7 years old) and 227 healthy control subjects (aged 61.0±7.4 years old) were enrolled from 3 retrospective studies. The participants were divided into training with ten-fold cross-validation (N = 432) and an independent blind dataset (N = 100). Diffusion-weighted images were acquired from a 3T scanner. Fractional anisotropy and mean diffusivity were calculated and was subsequently parcellated into 90 cerebral regions of interest based on the Automatic Anatomic Labeling template. A convolutional neural network was implemented which contained three convolutional blocks and a fully connected layer. Each convolutional block consisted of a convolutional layer, activation layer, and pooling layer. This model was trained for each individual region. A greedy algorithm was implemented to combine multiple regions as the final prediction. The greedy algorithm predicted the area under curve of 94.1±3.2% from the combination of fractional anisotropy from 22 regions. The model performance analysis showed that the combination of 9 regions is equivalent. The best area under curve was 74.7±5.4% from the right postcentral gyrus. The current study proposed an architecture of convolutional neural network and a greedy algorithm to combine from multiple regions. With diffusion tensor imaging, the algorithm showed the potential to distinguish patients with Parkinson’s disease from normal control with satisfactory performance.

Article
Due to cost and participant burden, neuroimaging studies are often performed in relatively small samples of voluntary participants. This may lead to selection bias. It is important to identify factors associated with participation in neuroimaging studies and understand their effect on outcome measures. We investigated the effect of postoperative delirium on long-term (over 48 months) cognitive decline (LTCD) in 560 older surgical patients (≥ 70 years), including a nested MRI cohort (n = 146). We observed a discrepancy in the effect of delirium on cognitive decline as a function of MRI participation. Although overall difference in cognitive decline due to delirium was not greater than what might be expected due to chance (p = .21), in the non-MRI group delirium was associated with a faster pace of LTCD (-0.063, 95% CI -0.094 to -0.032, p < .001); while in the MRI group the effect of delirium was less and not significant (-0.023, 95% CI -0.076, 0.030, p = .39). Since this limits our ability to investigate the neural correlates of delirium and cognitive decline using MRI data, we attempted to mitigate the observed discrepancy using inverse probability weighting for MRI participation. The approach was not successful and the difference of the effect of delirium in slope was essentially unchanged. There was no evidence that the MRI sub-group experienced delirium that differed in severity relative to MRI non-participants. We could not attribute the observed discrepancy to selection bias based on measured factors. It may reflect a power issue due to the smaller MRI subsample or selection bias from unmeasured factors.

Article
Functional constipation (FCon) is one of the common functional gastrointestinal disorders (FGID). Previous studies reported alterations in cortical morphometry as well as changes in white matter (WM) fiber tracts and thalamo-limbic/parietal structural connectivity (SC). However, whether patients with FCon are implicated in changes in gray matter (GM) volume and associated SC remains unclear. Voxel-based morphometry (VBM) was first employed to examine differences in GM volume between 48 patients with FCon and 52 healthy controls (HC). Diffusion tensor imaging (DTI) with probabilistic tractography analysis was then employed to explore alterations in SC of these regions. Results showed abdominal symptoms were positively correlated with anxiety (SAS). Two sample t-test showed patients with FCon had decreased GM volumes in the right middle frontal gyrus (MFG_R), left insula (INS_L), and anterior cingulate cortex (ACC, PFWE < 0.05) which were negatively correlated with abdominal symptoms and difficulty of defecation respectively. Seed-based SC analysis showed patients with FCon had decreased fractional anisotropy of the ACC-right MFG and bilateral INS-MFG tracts. These findings reflect FCon is associated with changes in GM volumes and corresponding SC in brain regions within the salience network.

Article
Life expectancy in adults with congenital heart disease (ACHD) has increased. As these patients grow older, they experience aging-related diseases more than their healthy peers. To better characterize this field, we launched the multi-disciplinary BACH (Brain Aging in Congenital Heart disease) San Donato study, that aimed at investigating signs of brain injury in ACHD. Twenty-three adults with repaired tetralogy of Fallot and 23 age- and sex-matched healthy controls were prospectively recruited and underwent brain magnetic resonance imaging. White matter hyperintensities (WMHs) were segmented using a machine-learning approach and automatically split into periventricular and deep. Cerebral microbleeds were manually counted. A subset of 14 patients were also assessed with an extensive neuropsychological battery. Age was 41.78 ± 10.33 years (mean ± standard deviation) for patients and 41.48 ± 10.28 years for controls ( p = 0.921). Albeit not significantly, total brain ( p = 0.282) and brain tissue volumes ( p = 0.539 for cerebrospinal fluid, p = 0.661 for grey matter, p = 0.793 for white matter) were lower in ACHD, while total volume ( p = 0.283) and sub-classes of WMHs ( p = 0.386 for periventricular WMHs and p = 0.138 for deep WMHs) were higher in ACHD than in controls. Deep WMHs were associated with poorer performance at the frontal assessment battery (r = -0.650, p = 0.012). Also, patients had a much larger number of microbleeds than controls (median and interquartile range 5 [3–11] and 0 [0–0] respectively; p < 0.001). In this study, adults with tetralogy of Fallot showed specific signs of brain injury, with some clinical implications. Eventually, accurate characterization of brain health using neuroimaging and neuropsychological data would aid in the identification of ACHD patients at risk of cognitive deterioration.

Article
Background Accumulating evidence indicated that anhedonia as a transdiagnostic construct might be an inherent feature of obsessive–compulsive disorder(OCD). Moreover, our recent study demonstrated that OCD patients exhibited consummatory anhedonia but not anticipatory anhedonia. However, neural mechanisms of consummatory anhedonia in OCD has not been explored. This study aimed to investigate this issue using resting-state functional magnetic resonance imaging (fMRI). Methods 44 OCD patients with high consummatory anhedonia(OCD-HCA), 41 OCD patients with low consummatory anhedonia(OCD-LCA) and 47 healthy controls (HC) underwent fMRI scan. Spontaneous neural activity was analyzed and compared among the three groups by adopting the amplitude of low-frequency fluctuation (ALFF). Relationships between the consummatory anhedonia levels and regional ALFFs were examined in OCD patients. Results Compared with HC, OCD-HCA showed decreased ALFF in the right putamen and right thalamus, and OCD-LCA showed increased ALFF in the right orbitofrontal cortex and decreased ALFF in the right fusiform gyrus, left Precentral/postcentral gyrus. Notably, ALFF values differed between the two patient groups in the right putamen (OCD-HCA < OCD-LCA), and right fusiform gyrus (OCD-HCA > OCD-LCA). Further analysis revealed that the consummatory anhedonia was positively correlated with ALFF values in the right fusiform, and negatively correlated with ALFFs in the right putamen. Conclusions Spontaneous neural activity in right fusiform gyrus and right putamen is associated with consummatory anhedonia in OCD. The findings provided first insights into neural mechanism of consummatory anhedonia in OCD and confirmed the importance of exploring the transdiagnostic role of anhedonia.

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Article
Functional magnetic resonance imaging (fMRI) has been used to study the influence of opioids on neural circuitry implicated in opioid use disorder, such as the cortico-striatal-thalamo-cortical (CSTC) circuit. Given the increase in fentanyl-related deaths, this study was conducted to characterize the effects of fentanyl on patterns of brain activation in awake nonhuman primates. Four squirrel monkeys were acclimated to awake scanning procedures conducted at 9.4 Tesla. Subsequently, test sessions were conducted in which a dose of fentanyl that reliably maintains intravenous (IV) self-administration behavior in monkeys, 1 μg/kg, was administered and the effects on patterns of brain activity were assessed using: (1) a pharmacological regressor to elucidate fentanyl-induced patterns of neural activity, and (2) seed-based approaches targeting bilateral anterior cingulate, thalamus, or nucleus accumbens (NAc) to determine alterations in CSTC functional connectivity. Results showed a functional inhibition of BOLD signal in brain regions that mediate behavioral effects of opioid agonists, such as cingulate cortex, striatum and midbrain. Functional connectivity between each of the seed regions and areas involved in motoric, sensory and cognition-related behavior generally decreased. In contrast, NAc functional connectivity with other striatal regions increased. These results indicate that fentanyl produces changes within CSTC circuitry that may reflect key features of opioid use disorder (e.g. persistent drug-taking/seeking) and thereby contribute to long-term disruptions in behavior and addiction. They also indicate that fMRI in alert nonhuman primates can detect drug-induced changes in neural circuits and, in turn, may be useful for investigating the effectiveness of medications to reverse drug-induced dysregulation.

Article
Obstructive sleep apnea (apnea) is thought to cause small vessel ischemic episodes in the brain from hypoxic events, postulated as white matter hyperintensities (hyperintensities) identified on MRI which are implicated in cognitive decline. This study sought to evaluate these correlations. A retrospective evaluation of adults who underwent polysomnography (4/1/2016 to 4/30/2017) and a brain MRI prior to apnea diagnosis or within a year post-diagnosis was completed. MRI visual evaluation of hyperintensities using Fazekas scores were collected blind to clinical data. Collated clinical/MRI data were stratified and analyzed using chi-square, fishers t-tests, ANOVA/ANCOVA and linear regression. Stratification by apnea category revealed no significant differences in any variables including hyperintensity measures (Fazekas p=0.1584; periventricular p=0.3238; deep p=0.4618; deep total p=0.1770). Stratification by Fazekas category, periventricular and deep hyperintensities revealed increasing prevalence with age (p=0.0001); however, apnea categories were not significantly associated (Fazekas p=0.1479; periventricular p=0.3188; deep p=0.4503), nor were any individual apnea indicators. Continuous apnea measurements werre not associated with any hyperintensity factor; total deep hyperintensities were not associated with any apnea factors. Continuous BMI was not found to be associated with any apnea or hyperintensity factors. Only hypertension was noted to be associated with Fazekas (p=0.0045), deep (p=0.0010) and total deep (p=0.0021) hyperintensities; however, hypertension was not associated with apnea category (p=0.3038) or any associated factors. These data suggest apneas alone from OSA are insufficient to cause WMH, but other factors appear to contribute to the complex development of small vessel ischemic injury associated with age and cognitive decline.

Article
Previous studies identified some genetic loci of emotion, but few focused on human emotion-related gene expression. In this study, the facial expression recognition (FER) task-based high-resolution fMRI data of 203 subjects in the Human Connectome Project (HCP) and expression data of the six healthy human postmortem brain tissues in the Allen Human Brain Atlas (AHBA) were used to conduct a transcriptome-neuroimaging spatial association analysis. Finally, 371 genes were identified to be significantly associated with FER-related brain activations. Enrichment analyses revealed that FER-related genes were mainly expressed in the brain, especially neurons, and might be related to cell junction organization, synaptic functions, and nervous system development regulation, indicating that FER was a complex polygenetic biological process involving multiple pathways. Moreover, these genes exhibited higher enrichment for psychiatric diseases with heavy emotion impairments. This study provided new insight into understanding the FER-related biological mechanisms and might be helpful to explore treatment methods for emotion-related psychiatric disorders.

Article
In this prospective study, we postulate that there is a difference between clearance of [99mTc]Tc- ethyl cysteinate dimer (ECD) in the seizure onset zone (SOZ) and other brain areas and thus SOZ localization by clearance patterns might become a potential novel method for SOZ localization in epilepsy. The parametric images of brain ECD clearance were generated by linear regression model analysis from serial brain SPECT scans from 30 to 240 min after ECD injection (7-times point) in 7 patients with drug-resistant epilepsy and 3 normal volunteers. Clearance patterns of the SOZ confirmed by good surgical outcome or consensus with other investigations were analyzed quantitatively and semi-quantitatively by visual grading (slower or faster washout than contralateral brain regions). The average [99mTc]Tc-ECD clearance rates of SOZs were + 1.08% ± 2.57%/hr (wash in), -7.02% ± 2.56%/hr (washout), and -5.37% ± 1.71%/hr (washout) in ictal, aura and interictal states, respectively. Paired t-tests between the SOZ and contralateral regions showed statistically significant difference (p = 0.039 in interictal state). Clearance patterns that can define the SOZs were 1) wash in and slow washout on ictal slope, 2) fast washout on aura slope and interictal slope with 100% (6/6), 100% (2/2) and 75% (6/8) localization using ictal, aura, and interictal slope maps, respectively. Our study provided the evidence that clearance pattern methods are potential additive diagnostic tools for SOZ localization when routine one-time point SPECT are unable to define the SOZ.

Article
Schizophrenia which is an abnormally developmental disease has been widely reported to show abnormal brain structure and function. Enhanced functional integration is a predominant neural marker for brain mature. Abnormal development of structure and functional integration may be a biomarker for early diagnosis of schizophrenia. Fifty-five patients with early onset schizophrenia (EOS) and 79 healthy controls were enrolled in this study. Voxel-based morphometry (VBM) and functional connectivity density (FCD) were performed to explore gray matter volume (GMV) lesion, abnormal functional integration, and concurrent structural and functional abnormalities in the brain. Furthermore, the relationships between abnormalities structural and function and clinical characteristics were evaluated in EOS. Compared with healthy controls, EOS showed significantly decreased GMV in the bilateral OFC, frontal, temporal, occipital, parietal and limbic system. EOS also showed decreased FCD in precuneus and increased FCD in cerebellum. Moreover, we found concurrent changes of structure and function in left lateral orbitofrontal cortex (lOFC). Finally, correlation analyses did not find significant correlation between abnormal neural measurements and clinical characteristic in EOS. The results reveal disassociated and bound structural and functional abnormalities patterns in EOS suggesting structural and functional measurements play different roles in delineating the abnormal patterns of EOS. The concurrent structural and functional changes in lOFC may be a biomarker for early diagnosis of schizophrenia. Our findings will deepen our understanding of the pathophysiological mechanisms in EOS.

Article
Previous studies have reported evidence supporting structural and functional alterations in the brains of methamphetamine (MA) users. The aim of the present study was to extend current knowledge regarding brain function(s) in MA users by examining regional homogeneity (ReHo). Chronic MA users (51 male, 46 female), who were undergoing supervised abstinence for 12 to 621 days, and 79 healthy controls (43 male, 36 female) underwent resting-state functional brain magnetic resonance imaging. Voxel-wise whole-brain scale group differences in ReHo were examined. The mean ReHo values of significant clusters were extracted, and linear regression was used to identify factors that contributed to these mean ReHo values. MA users exhibited lower ReHo values in the left orbital part of the inferior frontal gyrus extending to the left insula and left temporal pole, left amygdala, and left fusiform gyrus. MA users also exhibited greater ReHo values in the bilateral pre- and postcentral gyri and right cerebellum. Characteristics of MA use, including duration, duration of abstinence from MA, and age at onset of MA use, demonstrated no reliable contribution to ReHo of the significant clusters. Findings of the present study demonstrated that chronic MA use was associated with regional specific disruption of ReHo, which is relatively independent of structural and functional alterations and, apparently, does not recover after relatively long-term abstinence. This disruption may underlie overall neurocognitive deficits in MA users, which is difficult to recover.

Article
The pathophysiological mechanisms of bipolar disorder (BD) are not completely known, and systemic inflammation and immune dysregulation are considered as risk factors. Previous neuroimaging studies have proved metabolic, structural and functional abnormalities of the amygdala in BD, suggesting the vital role of amygdala in BD patients. This study aimed to test the underlying neural mechanism of inflammation-induced functional connectivity (FC) in the amygdala subregions of BD patients. Resting-state functional MRI (rs-fMRI) was used to delineate the amygdala FC from two pairs of amygdala seed regions (the bilateral lateral and medial amygdala) in 51 unmedicated BD patients and 69 healthy controls (HCs). The levels of pro-inflammatory cytokines including interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α were measured in the serum. The correlation between abnormal levels of pro-inflammatory cytokines and FC values were calculated in BD patients. The BD group exhibited decreased FC between the right medial amygdala and bilateral medial frontal cortex (MFC), and decreased FC between the left medial amygdala and the left temporal pole (TP), right orbital inferior frontal gyrus compared with HCs. The BD patients had higher levels of TNF-α than HCs. Correlation analysis showed negative correlation between the TNF-α level and abnormal FC of the right medial amygdala-bilateral MFC; and negative correlation between TNF-α levels and abnormal FC of the left medial amygdala-left TP in BD group. These findings suggest that dysfunctional and immune dysregulation between the amygdala and the frontotemporal circuitry might play a critical role in the pathogenesis of BD.

Article

Article
The purpose of this study was to determine if differences in functional connectivity strength (FCS) with age were confounded by vascular parameters including resting cerebral blood flow (CBF0), cerebrovascular reactivity (CVR), and BOLD-CBF coupling. Neuroimaging data were collected from 13 younger adults (24 ± 2 years) and 14 older adults (71 ± 4 years). A dual-echo resting state pseudo-continuous arterial spin labeling sequence was performed, as well as a BOLD breath-hold protocol. A group independent component analysis was used to identify networks, which were amalgamated into a region of interest (ROI). Within the ROI, FC strength (FCS) was computed for all voxels and compared across the groups. CBF0, CVR and BOLD-CBF coupling were examined within voxels where FCS was different between young and older adults. FCS was greater in old compared to young (P = 0.001). When the effect of CBF0, CVR and BOLD-CBF coupling on FCS was examined, BOLD-CBF coupling had a significant effect (P = 0.003) and group differences in FCS were not present once all vascular parameters were considered in the statistical model (P = 0.07). These findings indicate that future studies of FCS should consider vascular physiological markers in order to improve our understanding of aging processes on brain connectivity.

Article
Attention is a basic human function underlying every other cognitive process. It is demonstrated in the functional Magnetic Resonance Imaging literature that frontoparietal networks are involved with attentive performance while default mode networks are involved with inattentive performance. Yet, it is still not clear whether similar results would be found with functional Near-Infrared Spectroscopy. The goal of our study was to investigate differences in hemodynamic activity measured by functional Near-Infrared Spectroscopy between fast and slow responses on a simple sustained attention task both before and after stimulus onset. Thirty healthy adults took part in the study. Our results have shown differences between fast and slow responses only on channels over medial frontal cortex and inferior parietal cortex (p < 0,05). These differences were observed both before and after stimulus presentation. It is discussed that functional Near-Infrared Spectroscopy is a good tool to investigate the frontoparietal network and its relationship with performance in attention tasks; it could be used to further investigate other approaches on attention, such as the dual network model of cognitive control and brain states views based on complex systems analysis; and finally, it could be used to investigate attention in naturalistic settings.

Article
Disrupted whole-brain resting-state functional connectivity (RSFC) of the posterior cingulate (PCC) has been highlighted to associate with cognitive and affective dysfunction in major depressive disorder (MDD). However, prior findings showed certain inconsistency about the RSFC of the PCC in MDD. This study aims to investigate the aberrant RSFC of the PCC in MDD using anisotropic effect-size version of seed-based d mapping (AES-SDM). Web of Science and PubMed were searched for studies investigating PCC-based RSFC in MDD. A total of 17 studies, involving 804 patients and 724 healthy controls (HCs), fit our selection criteria. Additionally, to seek for the link between functional and structural differences, we did a meta-analysis on the studies in conjunction with voxel-based morphology (VBM) analysis. The PCC showed higher RSFC with the left middle temporal gyrus (MTG) and the right middle frontal gyrus (MFG), and lower RSFC with the left superior frontal gyrus (SFG) and the left precuneus in patients with MDD than HCs. Moreover, the meta-regression analysis revealed a negative correlation between the FC alteration of the right MFG with the PCC and depression severity. Notably, the left MTG and the left MFG demonstrated gray matter deviations in conjunction analysis. Our results indicated that the aberrant RSFC between the PCC and brain regions sub-serving cognitive control and emotional regulation in patients with MDD. And such functional alterations may have structural basis. These findings may underlie the mechanisms of deficits in cognitive control and emotional regulation of MDD.

Article
Bilateral coordination of the lower extremities is an essential component of mobility. The corpus callosum bridges the two hemispheres of the brain and is integral for the coordination of such complex movements. The aim of this project was to assess structural integrity of the transcallosal sensorimotor fiber tracts and identify their associations with gait coordination using novel methods of ecologically valid mobility assessments in persons with multiple sclerosis and age−/gender-matched neurotypical adults. Neurotypical adults (n = 29) and persons with multiple sclerosis (n = 27) underwent gait and diffusion tensor imaging assessments; the lower limb coordination via Phase Coordination Index, and radial diffusivity, an indirect marker of myelination, were applied as the primary outcome measures. Persons with multiple sclerosis possessed poorer transcallosal white matter microstructural integrity of sensorimotor fiber tracts compared to the neurotypical adults. Further, persons with multiple sclerosis demonstrated significantly poorer bilateral coordination of the lower limbs during over-ground walking in comparison to an age and gender-matched neurotypical cohort. Finally, bilateral coordination of the lower limbs was significantly associated with white matter microstructural integrity of the dorsal premotor and primary motor fiber bundles in persons with multiple sclerosis, but not in neurotypical adults. This analysis revealed that persons with multiple sclerosis exhibit poorer transcallosal microstructural integrity than neurotypical peers. Furthermore, these structural deficits were correlated to poorer consistency and accuracy of gait in those with multiple sclerosis. Together, these results, emphasize the importance of transcallosal communication for gait coordination in those with multiple sclerosis.

Article
Pentagon Copying Test (PCT) is commonly used to assess visuospatial deficits, but the neural substrates underlying pentagon copying are not well understood. The Qualitative Scoring Pentagon Test (QSPT), an optimized scoring system, classifies five categories of errors patients make in pentagons copying and grades them depending on the errors’ severity. To determine the strategic brain regions involved in the PCT, we applied the QSPT system to evaluate the visuospatial impairment of 136 acute ischemic stroke patients on the PCT and used Support Vector Regression Lesion-Symptom Mapping to investigate relevant brain regions. The total QSPT score was correlated with the right supramarginal gyrus. The angle number errors and closure errors were principally associated with lesions of the posterior temporoparietal cortex, including the right middle occipital gyrus and middle temporal gyrus, while the intersection errors and rotation errors were related to the more anterior part of the right temporoparietal lobe with the additional frontal cortex. In conclusion, the right temporoparietal cortex is the strategic region for pentagon copying tasks. The angle number and closure represent the visuospatial processing of within-object features, while intersection and rotation require between-object manipulation. The posterior-anterior distinction in the right temporoparietal region underlies the differences of within-object and between-object processing.

Article
Dysfunction of the cingulo-frontal-parietal (CFP) cognitive attention network has been associated with the pathophysiology of chronic low back pain (cLBP). However, the direction of information processing within this network remains largely unknown. We aimed to study the effective connectivity among the CFP regions in 36 cLBP patients and 36 healthy controls by dynamic causal modeling (DCM). Both the resting-state and task-related (Multi-Source Interference Task, MSIT) functional magnetic resonance imaging (fMRI) data were collected and analyzed. The relationship between the effective connectivity of the CFP regions and clinical measures was also examined. Our results suggested that cLBP had significantly altered resting-state effective connectivity of the prefrontal cortex (PFC)-to-mid-cingulate cortex (MCC) (increased) and MCC-to-left superior parietal cortex (LPC) (decreased) pathways as compared with healthy controls. MSIT-related DCM suggested that the interference task could significantly increase the effective connectivity of the right superior parietal cortex (RPC)-to-PFC and RPC-to-MCC pathways in cLBP than that in healthy controls. The control task could significantly decrease the effective connectivity of the MCC-to-LPC and MCC-to-RPC pathways in cLBP than that in healthy controls. The endogenous connectivity of the PFC-to-RPC pathway in cLBP was significantly lower than that in healthy controls. No significant correlations were found between the effective connectivity within CFP networks and pain/depression scores in patients with cLBP. In summary, our findings suggested altered effective connectivity in multiple pathways within the CFP network in both resting-state and performing attention-demanding tasks in patients with cLBP, which extends our understanding of attention dysfunction in patients with cLBP.

Article
We aim to explore the potential interaction effects of brain aging and gut microbiota on the risks of sleep, anxiety and depression disorders. The genome-wide association study (GWAS) datasets of brain aging (N = 21,407) and gut microbiota (N = 3,890) were obtained from published studies. Individual level genotype and phenotype data of psychiatric traits (including sleep, anxiety and depression) were all from the UK Biobank (N = 107,947–374,505). We first calculated the polygenic risk scores (PRS) of 62 brain aging modes and 114 gut microbiota taxa as the instrumental variables, and then constructed linear and logistic regression analyses to systematically explore the potential interaction effects of brain aging and gut microbiota on psychiatric disorders. We observed the interaction effects of brain aging and gut microbiota on sleep, anxiety and depression disorders, such as Putamen/caudate T2* vs. Rhodospirillales (β = -0.012, P = 8.4 × 10–4) was negatively associated with chronotype, Fornix MD vs. Holdemanella (β = -0.007, P = 1.76 × 10–2) was negatively related to general anxiety disorder (GAD) scores, and White matter lesions vs. Acidaminococcaceae (β = 0.019, P = 1.29 × 10–3) was positively correlated with self-reported depression. Interestingly, Putamen volume vs. Intestinibacter was associated with all three psychiatric disorders, including chronotype (negative correlation), GAD scores (positive correlation) and self-reported depression (positive correlation). Our study results suggest the significant impacts of brain aging and gut microbiota on the development of sleep, anxiety and depression disorders, providing new clues for clarifying the pathogenesis of these disorders.

Article
Metacognitive deficits affect Alzheimer’s disease (AD) patient safety and increase caregiver burden. The brain areas that support metacognition are not well understood. 112 participants from the Imaging and Genetic Biomarkers for AD (ImaGene) study underwent comprehensive cognitive testing and brain magnetic resonance imaging. A performance-prediction paradigm was used to evaluate metacognitive abilities for California Verbal Learning Test–II learning (CVLT-II 1–5) and delayed recall (CVLT-II DR); Visual Reproduction-I immediate recall (VR-I Copy) and Visual Reproduction-II delayed recall (VR-II DR); Rey-Osterrieth Complex Figure Copy (Rey-O Copy) and delayed recall (Rey-O DR). Vertex-wise multivariable regression of cortical thickness was performed using metacognitive scores as predictors while controlling for age, sex, education, and intracranial volume. Subjects who overestimated CVLT-II DR in prediction showed cortical atrophy, most pronounced in the bilateral temporal and left greater than right (L > R) frontal cortices. Overestimation of CVLT-II 1–5 prediction and DR performance in postdiction showed L > R associations with medial, inferior and lateral temporal and left posterior cingulate cortical atrophy. Overconfident prediction of VR-I Copy performance was associated with right greater than left medial, inferior and lateral temporal, lateral parietal, anterior and posterior cingulate and lateral frontal cortical atrophy. Underestimation of Rey-O Copy performance in prediction was associated with atrophy localizing to the temporal and cingulate areas, and in postdiction, with diffuse cortical atrophy. Impaired metacognition was associated to cortical atrophy. Our results indicate that poor insight into one’s cognitive abilities is a pervasive neurodegenerative feature associated with AD across the cognitive spectrum.

Article
Objective: To examine attention, executive control, and performance variability in healthy varsity athletes and identify unique resting-state functional connectivity (rsFC) patterns associated with measures of speed, stability, and attention. Method: A sample of 29 female university varsity athletes completed cognitive testing using the Attention Network Test- Interactions (ANT-I) and underwent resting-state functional MRI (rsfMRI) scans. Performance was characterized by examining mean reaction time (RT), variability in performance (ISD), and attention network scores on the ANT-I. RsfMRI data were analyzed using an independent component analysis (ICA) in the frontoparietal (FPN), dorsal attention (DAN), default mode, (DMN), salience (SN), and sensorimotor (SMN) networks. Group-level analyses using the performance variables of interest were conducted. Results: Athletes’ performance on the ANT-I revealed a main effect of orienting and executive control (ps<.001; partial η2 = .68 and .89, respectively), with performance facilitated (i.e., faster RT) when athletes were presented with valid cues and congruent flankers. Alerting, orienting, and executive control performance were associated with differences in rsFC within the SN, DMN, and FPN, respectively. Slower RTs were associated with greater rsFC between DAN and bilateral postcentral gyri (p<.001), whereas more stable performance was associated with greater FC between the SMN and the left precuneus (p<.05). Conclusions: Consistent with prior studies, we observed that efficiency in alerting, orienting, and executive control aspects of attention was associated with differences in rsFC in regions associated with the SN, DMS, and FPN. In addition, we observed differential patterns of rsFC for overall speed and variability of performance.

Article
Task-based functional MRI (tb-fMRI) represents an extremely valuable approach for the identification of language eloquent regions for presurgical mapping in patients with brain tumors. However, its routinely application is limited by patient-related factors, such as cognitive disability and difficulty in coping with long-time acquisitions, and by technical factors, such as lack of equipment availability for stimuli delivery. Resting-state fMRI (rs-fMRI) instead, allows the identification of distinct language networks in a 10-min acquisition without the need of performing active tasks and using specific equipment. Therefore, to test the feasibility of rs-fMRI as a preoperative mapping tool, we reconstructed a lexico-semantic intrinsic connectivity network (ICN) in healthy controls (HC) and in a case series of patients with gliomas and compared the organization of this language network with the one derived from tb-fMRI in the patient’s group. We studied three patients with extra-frontal gliomas who underwent functional mapping with auditory verb-generation (AVG) task and rs-fMRI with a seed in the left inferior frontal gyrus (IFG). First, we identified the functional connected areas to the IFG in HC. We qualitatively compared these areas with those that showed functional activation in AVG task derived from Neurosynth meta-analysis. Last, in each patient we performed single-subject analyses both for rs- and tb-fMRI, and we evaluated the spatial overlap between the two approaches. In HC, the IFG-ICN network showed a predominant left fronto-temporal functional connectivity in regions overlapping with the AVG network derived from a meta-analysis. In two patients, rs- and tb-fMRI showed comparable patterns of activation in left fronto-temporal regions, with different levels of contralateral activations. The third patient could not accomplish the AVG task and thus it was not possible to make any comparison with the ICN. However, in this patient, task-free approach disclosed a consistent network of fronto-temporal regions as in HC, and additional parietal regions. Our preliminary findings support the value of rs-fMRI approach for presurgical mapping, particularly for identifying left fronto-temporal core language-related areas in glioma patients. In a preoperative setting, rs-fMRI approach could represent a powerful tool for the identification of eloquent language areas, especially in patients with language or cognitive impairments.

Article
Although childhood maltreatment confers a high risk for the development of major depressive disorder, the neurobiological mechanisms underlying this connection remain unknown. The present study sought to identify the specific resting-state networks associated with childhood maltreatment. We recruited major depressive disorder patients with and without a history of childhood maltreatment (n = 31 and n = 30, respectively) and healthy subjects (n = 80). We used independent component analysis to compute inter- and intra- network connectivity. We found that individuals with major depressive disorder and childhood maltreatment could be characterized by the following network disconnectivity model relative to healthy subjects: (i) decreased intra-network connectivity in the left frontoparietal network and increased intra-network connectivity in the right frontoparietal network, (ii) decreased inter-network connectivity in the posterior default mode network—auditory network, posterior default mode network—limbic system, posterior default mode network—anterior default mode network, auditory network—medial visual network, lateral visual network - medial visual network, medial visual network—sensorimotor network, medial visual network - anterior default mode network, occipital pole visual network—dorsal attention network, and posterior default mode network—anterior default mode network, and (iii) increased inter-network connectivity in the sensorimotor network—ventral attention network, and dorsal attention network—ventral attention network. Moreover, we found significant correlations between the severity of childhood maltreatment and the intra-network connectivity of the frontoparietal network. Our study demonstrated that childhood maltreatment is integrally associated with aberrant network architecture in patients with major depressive disorder.

Article
Type 2 diabetes is associated with a higher risk of dementia. The pathogenesis is complex and partly influenced by genetic factors. The hippocampus is the most vulnerable brain region in individuals with type 2 diabetes. However, whether the genetic risk of type 2 diabetes is associated with the hippocampus and episodic memory remains unclear. This study explored the influence of polygenic risk score (PRS) of type 2 diabetes on the white matter topological properties of the hippocampus among individuals with and without type 2 diabetes and its associations with episodic memory. This study included 103 individuals with type 2 diabetes and 114 well-matched individuals without type 2 diabetes. All the participants were genotyped, and a diffusion tensor imaging-based structural network was constructed. PRS was calculated based on a genome-wide association study of type 2 diabetes. The PRS-by-disease interactions on the bilateral hippocampal topological network properties were evaluated by analysis of covariance (ANCOVA). There were significant PRS-by-disease interaction effects on the nodal topological properties of the right hippocampus node. In the individuals with type 2 diabetes, the PRS was correlated with the right hippocampal nodal properties, and the nodal properties were correlated with the episodic memory. In addition, the right hippocampal nodal properties mediated the effect of PRS on episodic memory in individuals with type 2 diabetes. Our results suggested a gene-brain-cognition biological pathway, which might help understand the neural mechanism of the genetic risk of type 2 diabetes affects episodic memory in type 2 diabetes.

Article
Both men and women scoring high on psychopathy exhibit similar structural and functional neural abnormalities, including reduced volume of the orbitofrontal cortex (OFC) and reduced hemodynamic activity in the amygdala during affective processing experimental paradigms. The uncinate fasciculus (UF) is a white matter (WM) tract that connects the amygdala to the OFC. Reduced structural integrity of the UF, measured via fractional anisotropy (FA), is commonly associated with men scoring high on psychopathy. However, only one study to date has investigated the relationship between psychopathic traits and UF structural integrity in women, recruiting participants from a community sample. Here, we investigated whether Hare Psychopathy Checklist-Revised (PCL-R) facet scores (measuring interpersonal, affective, lifestyle/behavioral, and antisocial psychopathic traits, respectively) were associated with reduced FA in the left and right UF in a sample of 254 incarcerated women characterized by a wide range of psychopathy scores. We observed that PCL-R Facet 3 scores, assessing lifestyle/behavioral psychopathic traits, were associated with reduced FA in the left and right UF, even when controlling for participant’s age and history of previous substance use. The results obtained in the current study help improve our understanding of structural abnormalities associated with women scoring high on psychopathy. Specifically, reduced UF structural integrity may contribute to some of the deficits commonly associated with women scoring high on psychopathy, including emotion dysregulation.

Article
The topological properties of functional brain networks in post-traumatic stress disorder (PTSD) have been thoroughly examined, whereas the topology of structural covariance networks has been researched much less. Based on graph theoretical approaches, we investigated the topological architecture of structural covariance networks among PTSD, trauma-exposed controls (TEC), and healthy controls (HC) by constructing covariance networks driven by inter-regional correlations of cortical thickness. Structural magnetic resonance imaging (sMRI) scans and clinical scales were performed on 27 PTSD, 33 TEC, and 29 HC subjects. Group-level structural covariance networks were established using pearson correlations of cortical thickness between 68 brain areas, and the graph theory method was utilized to study the global and nodal properties. PTSD and HC subjects did not differ at the global level. When PTSD subjects were compared to TEC subjects, they had significantly higher clustering coefficient (p = .014) and local efficiency (p = .031). Nodes having different nodal centralities between groups did not pass the false-discovery rate correction at the node level. According to the structural brain network topological characteristics discovered in this study, PTSD manifests differently compared to the TEC group. In the PTSD group, the SCN keeps the small-world characteristics, but the degree of functional separation is enhanced. The TEC group’s reduced small worldness and the tendency for brain network randomization could be signs of trauma recovery.

Article
Background Primary dysmenorrhea (PDM) is highly associated with mood symptoms. However, the neuropathology of these comorbidities is unclear. In the present study, we aimed to investigate the structural changes in the amygdala of patients with PDM during the pain-free phase using a surface-based shape analysis. Methods Forty-three PDM patients and forty healthy controls were recruited in the study, and all participants underwent structural magnetic resonance imaging scans during their periovulatory phase. FMRIB’s Integrated Registration and Segmentation Tool (FIRST) was employed to assess the subcortical volumetric and surface alterations in patients with PDM. Moreover, correlation and mediation analyses were used to detect the clinical significance of the subcortical morphometry alteration. Results PDM patients showed hypertrophic alteration of the amygdala in the left superficial nuclei and right basolateral and superficial nuclei but not for the whole amygdala volume. The hypertrophic amygdala was associated with disease duration, pain severity and anxiety symptoms during the menstrual period. Furthermore, the hypertrophic left amygdala could mediate the association between disease duration and anxiety severity. Conclusions The results of the current study demonstrated that the localized amygdala shape hypertrophy was present in PDM patients even in the pain-free phase. In addition, the mediator role of the hypertrophic amygdala indicates the potential target of amygdala for anxiety treatment in PDM treatment in the pain-free phase.

Article
The human brain develops dynamically during early childhood, when the child is sensitive to both genetic programming and extrinsic exposures. Recent studies have found links between prenatal and early life environmental factors, family demographics and the cortical brain morphology in newborns measured by surface area, volume and thickness. Here in this magnetic resonance imaging study, we evaluated whether a similar set of variables associates with cortical surface area and volumes measured in a sample of 170 healthy 5-year-olds from the FinnBrain Birth Cohort Study. We found that child sex, maternal pre-pregnancy body mass index, 5 min Apgar score, neonatal intensive care unit admission and maternal smoking during pregnancy associated with surface areas. Furthermore, child sex, maternal age and maternal level of education associated with brain volumes. Expectedly, many variables deemed important for neonatal brain anatomy (such as birth weight and gestational age at birth) in earlier studies did not associate with brain metrics in our study group of 5-year-olds, which implies that their effects on brain anatomy are age-specific. Future research may benefit from including pre- and perinatal covariates in the analyses when such data are available. Finally, we provide evidence for right lateralization for surface area and volumes, except for the temporal lobes which were left lateralized. These subtle differences between hemispheres are variable across individuals and may be interesting brain metrics in future studies.

Article
Little is known about the underlying neurobiological mechanisms in patients with obsessive-compulsive disorder (OCD). We aimed to examine cortical thickness and surface area in individuals with OCD and their unaffected siblings, comparing them to healthy controls. 30 patients with OCD, 21 unaffected siblings (SIB) and 30 controls underwent structural magnetic resonance imaging. Structural images were analyzed using the FreeSurfer software package (version 6.0). Compared to healthy controls, both OCD and SIB groups showed significantly lower cortical thickness in the right anterior insula. Surface areas of the superior frontal gyrus, paracentral gyrus and precuneus of the right hemisphere were also reduced in OCD patients compared to controls. There were no significant differences in cortical thickness and surface area between the OCD and SIB groups. We did not detect any significant differences in subcortical volumes between groups. Lower cortical thickness in the right anterior insula in both OCD patients and unaffected siblings may represent a potential structural endophenotype for OCD.

Article
Resting state low-frequency brain activity may aid in our understanding of the mechanisms of aging-related cognitive decline. Our purpose was to explore the characteristics of the amplitude of low-frequency fluctuations (ALFF) in different frequency bands of fMRI to better understand cognitive aging. Thirty-seven cognitively normal older individuals underwent a battery of neuropsychological tests and MRI scans at baseline and four years later. ALFF from five different frequency bands (typical band, slow-5, slow-4, slow-3, and slow-2) were calculated and analyzed. A two-way ANOVA was used to explore the interaction effects in voxel-wise whole brain ALFF of the time and frequency bands. Paired-sample t-test was used to explore within-group changes over four years. Partial correlation analysis was performed to assess associations between the altered ALFF and cognitive function. Significant interaction effects of time × frequency were distributed over inferior frontal gyrus, superior frontal gyrus, right rolandic operculum, left thalamus, and right putamen. Significant ALFF reductions in all five frequency bands were mainly found in the right hemisphere and the posterior cerebellum; whereas localization of the significantly increased ALFF were mainly found in the cerebellum at typical band, slow-5 and slow-4 bands, and left hemisphere and the cerebellum at slow-3, slow-2 bands. In addition, ALFF changes showed frequency-specific correlations with changes in cognition. These results suggest that changes of local brain activity in cognitively normal aging should be investigated in multiple frequency bands. The association between ALFF changes and cognitive function can potentially aid better understanding of the mechanisms underlying normal cognitive aging.

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• Harvard Medical School
• Brigham and Women's Hospital
• Boston University
• Ludwig-Maximilians-University of Munich
• École de Technologie Supérieure