Structural Brain Imaging Studies Research Articles

Update on the Neurobiology of Borderline Personality Disorder: A Review of Structural, Resting-State and Task-Based Brain Imaging Studies.

This review summarizes recent advances in research on the neurobiology of borderline personality disorder (BPD) according to structural brain imaging investigations and resting-state and task-based functional brain activation studies. Extending established findings on differences in regional brain volumes and cortical thickness between BPD and healthy controls, recent research illuminates shared and distinct brain structural characteristics compared to other psychiatric diagnoses, and uncovers relations of these brain structures with transdiagnostic symptoms and clinical features. Resting-state functional brain imaging studies reveal disruptions among adolescents and adults with BPD in frontolimbic and default-mode networks, which primarily underlie affect regulation and self-referential processes, respectively. Recent task-based functional brain imaging research builds on existing neurobiological understanding of emotion and cognition in BPD by revealing novel intersections with interpersonal- and stress-related processes. Studies of psychological and pharmacological interventions suggest possible effects on neural regions underlying emotion processing and behavioral control.

Highfield imaging of the subgenual anterior cingulate cortex in uni- and bipolar depression.

The subgenual Anterior Cingulate Cortex (sgACC), as a part of the Anterior Cingulate Cortex and the limbic system plays a crucial role in mood regulation. Previous structural and functional brain imaging studies of the sgACC have revealed alterations of Gray Matter (GM) volumes and Blood Oxygenation Level Dependent signals (BOLD) in patients with Major Depressive Disorder (MDD) and Bipolar Disorder (BD), suggesting potential biomarker traits for affective disorders. In this study we investigated the gray matter volume of the sgACC in 3 different patient groups: 40 MDD patients, of which 20 were medicated (MDDm) and 20 were unmedicated (MDDu), and 21 medicated BD patients, and compared them with 23 healthy volunteers. We examined GM volume alteration using high-resolution 7T Magnetic Resonance Imaging (MRI) which produced quantitative maps of the spin-lattice relaxation time (T1). T1 maps provide high contrast between gray and white matter, and at 7 Tesla voxels with submillimeter resolution can be acquired in a reasonable scan time. We developed a semi-automatic segmentation protocol based on refined landmarks derived from previous volumetric studies using quantitative T1 maps as raw input data for automatic tissue segmentation of GM, WM and CSF (cerebrospinal fluid) tissue. The sgACC ROI was then superimposed on these tissue probability maps and traced manually by two independent raters (F.B., M.M.) following our semi-automatic segmentation protocol. Interrater reliability was calculated on a subset of 10 brain scans for each hemisphere, showing an Intra-Class Correlation coefficient (ICC) r = 0.96 for left sgACC and r = 0.84 for right sgACC respectively. In summary, we have developed a reproducible and reliable semi-automatic segmentation protocol to measure gray matter volume in the sgACC. Based on previous findings from meta-analyses on morphometric studies of the sgACC, we hypothesized that patients with MDD would have lower gray matter sgACC volumes compared to healthy subjects. Post-hoc analysis revealed smaller subgenual volumes for the left hemisphere in both the medicated (MDDm) and non-medicated (MDDu) group versus healthy controls (p = .001, p = .008) respectively. For the right hemisphere, the (MDDu) and BD group exhibited significantly lower subgenual volumes than healthy controls (p < .001, p = .004) respectively. To our knowledge, this is the first morphometric MRI study using T1 maps obtained in high-resolution 7 Tesla MRI to compare MDD and BD patients with healthy controls.

Trigeminal neuralgia.

Trigeminal neuralgia (TN) is a facial pain disorder characterized by intense and paroxysmal pain that profoundly affects quality of life and presents complex challenges in diagnosis and treatment. TN can be categorized as classical, secondary and idiopathic. Epidemiological studies show variable incidence rates and an increased prevalence in women and in the elderly, with familial cases suggesting genetic factors. The pathophysiology of TN is multifactorial and involves genetic predisposition, anatomical changes, and neurophysiological factors, leading to hyperexcitable neuronal states, central sensitization and widespread neural plasticity changes. Neurovascular compression of the trigeminal root, which undergoes major morphological changes, and focal demyelination of primary trigeminal afferents are key aetiological factors in TN. Structural and functional brain imaging studies in patients with TN demonstrated abnormalities in brain regions responsible for pain modulation and emotional processing of pain. Treatment of TN involves a multifaceted approach that considers patient-specific factors, including the type of TN, with initial pharmacotherapy followed by surgical options if necessary. First-line pharmacological treatments include carbamazepine and oxcarbazepine. Surgical interventions, including microvascular decompression and percutaneous neuroablative procedures, can be considered at an early stage if pharmacotherapy is not sufficient for pain control or has intolerable adverse effects or contraindications.

Reduction of N-acetyl aspartate (NAA) in association with relapse in early-stage psychosis: a 7-Tesla MRS study

Understanding the biological underpinning of relapse could improve the outcomes of patients with psychosis. Relapse is elicited by multiple reasons/triggers, but the consequence frequently accompanies deteriorations of brain function, leading to poor prognosis. Structural brain imaging studies have recently been pioneered to address this question, but a lack of molecular investigations is a knowledge gap. Following a criterion used for recent publications by others, we defined the experiences of relapse by hospitalization(s) due to psychotic exacerbation. We hypothesized that relapse-associated molecules might be underscored from the neurometabolites whose levels have been different between overall patients with early-stage psychosis and healthy subjects in our previous report. In the present study, we observed a significant decrease in the levels of N-acetyl aspartate in the anterior cingulate cortex and thalamus in patients who experienced relapse compared to patients who did not. Altogether, decreased N-acetyl aspartate levels may indicate relapse-associated deterioration of neuronal networks in patients.

Cultural Variation in Behavioral Correlates of Cortical Thickness among 9-10-Year-Old Children

Background: One of the main characteristics that differentiate Asian and European cultures is self-construal, the former has a higher tendency to have interdependent, and the latter tends to have an independent self. Recent structural brain imaging studies have shown that the Prefrontal Cortex (PFC) is thinner in Asian than European individuals, attributed to a need for reduction of reward relevant to self to maximize the reward relevant to the group. There is more to find out about differential cortical thickness and behavioral correlates across these cultural groups Aim: This study was performed to investigate the associations between cultural group membership, age, cortical thickness, and two sets of reward-related behaviors (e.g., reward responsiveness and prosocial behaviors) in a national sample of 9/10-year-old children in the U.S. Materials and Methods: For this cross-sectional study, we used demographic, socioeconomic, structural, and behavioral data from the Adolescent Brain Cognitive Development (ABCD) study. Our analytical sample included 5942 American children between the ages of 9 and 10 who were either European (n=5741) or Asian (n=201). The cortical thickness for various Regions Of Interest (ROIs) was measured using Structural Magnetic Resonance Imaging (sMRI). Two aspects of the behavioral profile, reward sensitivity, and prosocial behaviors, were also measured using self-report data. As a proxy of self-construal, culture was the independent variable or the moderator variable, depending on the model. Mixed-effects regression models were used for data analysis to adjust for nested data across families and study sites. Results: In the overall sample, asian children had a smaller thickness of cortical regions across all ROIs than European children. Age did not interact with culture on cortical thickness, suggesting a similar rate of pruning across cultures. Culture showed statistically significant interactions with cortical thickness across ROIs within and beyond PFC on children’s reward responsiveness and prosocial behaviors, indicating stronger associations for Asian than European children. Conclusion: Compared to European children, Asian children show lower cortical thickness across ROIs, a phenomenon that is not limited to PFC and is not due to a differential rate of age-related pruning. There are stronger associations between the thickness of several cortical areas with prosocial behaviors and reward responsiveness in Asian children relative to European children, extending the existing literature on culture, cerebral cortex, and reward salience. Our findings support the hypothesis that Asian children’s cortical volume changes are a cultural adaptation to maximize conformity and harmony with the group in Asian culture by reducing the relevance of reward salience of self and maximizing it for the community. More research is needed on cultural differences in behavioral correlates of structural and functional measures of cortical regions among European and Asian children.

Motor symptoms in Parkinson’s disease are related to the interplay between cortical curvature and thickness

IntroductionBrain atrophy in Parkinson’s disease occurs to varying degrees in different brain regions, even at the early stage of the disease. While cortical morphological features are often considered independently in structural brain imaging studies, research on the co-progression of different cortical morphological measurements could provide new insights regarding the progression of PD. This study’s aim was to examine the interplay between cortical curvature and thickness as a function of PD diagnosis, motor symptoms, and cognitive performance. MethodsA total of 359 de novo PD patients and 159 healthy controls (HC) from the Parkinson’s Progression Markers Initiative (PPMI) database were included in this study. Additionally, an independent cohort from four databases (182 PD, 132 HC) with longer disease durations was included to assess the effects of PD diagnosis in more advanced cases. Pearson correlation was used to determine subject-specific associations between cortical curvature and thickness estimated from T1-weighted MRI images. General linear modeling (GLM) was then used to assess the effect of PD diagnosis, motor symptoms, and cognitive performance on the curvature-thickness association. Next, longitudinal changes in the curvature-thickness correlation as well as the predictive effect of the cortical curvature-thickness association on changes in motor symptoms and cognitive performance across four years were investigated. Finally, Akaike information criterion (AIC) was used to build a GLM to model PD motor symptom severity cross-sectionally. ResultsA significant interaction effect between PD motor symptoms and age on the curvature-thickness correlation was found (βstandardized = 0.11; t(350) = 2.12; p = 0.03). This interaction effect showed that motor symptoms in older patients were related to an attenuated curvature-thickness association. No significant effect of PD diagnosis was observed for the PPMI database (β = 0.03; t(510) = 0.35; p = 0.72). However, in patients with a longer disease duration, a significant effect of diagnosis on the curvature-thickness association was found (βstandardized = 0.31; t(306.7) = 3.49; p = 0.0006). Moreover, rigidity, but not tremor, in PD was significantly related to the curvature-thickness correlation (βstandardized = 0.11, t(350) = 2.24, p = 0.03; βstandardized = -0.03, t(350) = -0.58, p = 0.56, respectively). The curvature-thickness association was attenuated over time in both PD and HC, but the two groups did not show a significantly different effect (βstandardized = 0.03, t(184.7) = 0.78, p = 0.44). No predictive effects of the CC-CT correlation on longitudinal changes in cognitive performance or motor symptoms were observed (all p-values > 0.05). The best cross-sectional model for PD motor symptoms included the curvature-thickness correlation, cognitive performance, and putamen dopamine transporter (DAT) binding, which together explained 14 % of variance. ConclusionThe association between cortical curvature and thickness is related to PD motor symptoms and age. This research shows the potential of modeling the curvature-thickness interplay in PD.

Behavioral and biological divergence in monozygotic twin pairs discordant for autism phenotypes: A systematic review.

Non-shared environment (NSE) effects account for around one-third of the etiology of autism spectrum disorder (ASD). However, the knowledge of mechanisms and phenotypic profiles associated with NSE in ASD is scarce. A systematic search was conducted using Embase, MEDLINE, and PsycINFO for studies published in English between 1990 and August 2020 using co-twin control design to compare behavioral and biological phenotypes among monozygotic (MZ) twin pairs concordant/discordant for ASD, clinical autism symptoms, or autistic traits. Risk of bias was assessed through a modified Newcastle-Ottawa Scale. Twenty six articles were included. Differential DNA methylation and gene expression were found among ASD discordant twins; however, genetic results were inconsistent. Neurological disorders and early medical events were associated with ASD and autistic traits, while no within pair differences were found for minor physical anomalies or head circumference. Structural and functional brain imaging studies and research on social and other cognitive/behavioral functions were inconclusive. Risk of bias assessment found that all studies used the same exposure (or outcome) measures to collect data for participants and most used either secure health-related records or structured interviews for ascertainment of exposure; however, only a handful of studies representative of the population from which they were drawn. Formal assessment of risk of publication bias (i.e., funnel plot) was not possible. Our results suggest that NSE in ASD could be associated with heterogeneous postzygotic genetic mechanisms and manifest as a range of biological and behavioral phenotypes. Extant findings were limited by relatively few studies, small sample sizes, and methodological diversity. More research is needed on co-occurring biological and behavioral phenotypes using a consistent format for designing, analyzing, and reporting MZ ASD discordant twin studies in order to further examine the role of NSE in the etiology of ASD.

Cortical and Subcortical Brain Morphometry Abnormalities in Youth at Clinical High Risk for Psychosis and Individuals With Early Illness Schizophrenia

Many longitudinal structural brain imaging studies have reported progressive worsening of morphometric brain abnormalities in schizophrenia over the illness course, consistent with an underlying progressive pathophysiology. Although morphometric abnormalities in chronic schizophrenia are well-documented, less is known about brain morphometry abnormalities prior to psychosis onset in individuals at clinical high risk for psychosis (CHR), and how they compare with abnormalities early in the course of schizophrenia (ESZ).

Structural brain imaging studies offer clues about the effects of the shared genetic etiology among neuropsychiatric disorders

Genomewide association studies have found significant genetic correlations among many neuropsychiatric disorders. In contrast, we know much less about the degree to which structural brain alterations are similar among disorders and, if so, the degree to which such similarities have a genetic etiology. From the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) consortium, we acquired standardized mean differences (SMDs) in regional brain volume and cortical thickness between cases and controls. We had data on 41 brain regions for: attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), epilepsy, major depressive disorder (MDD), obsessive compulsive disorder (OCD), and schizophrenia (SCZ). These data had been derived from 24,360 patients and 37,425 controls. The SMDs were significantly correlated between SCZ and BD, OCD, MDD, and ASD. MDD was positively correlated with BD and OCD. BD was positively correlated with OCD and negatively correlated with ADHD. These pairwise correlations among disorders were correlated with the corresponding pairwise correlations among disorders derived from genomewide association studies (r = 0.494). Our results show substantial similarities in sMRI phenotypes among neuropsychiatric disorders and suggest that these similarities are accounted for, in part, by corresponding similarities in common genetic variant architectures.

Brain areas associated with resilience to depression in high-risk young women.

Previous structural brain-imaging studies in first-degree relatives of depressed patients showed alterations that are generally accepted as vulnerability markers for depression. However, only half of the relatives had depression at follow-up, while the other half did not. The aim of this study was to identify the brain areas associated with resilience to depression in high-risk subjects with familial depression. We recruited 59 young women with a history of depressed mothers. Twenty-nine of them (high-risk group [HRG]) had no depression history, while 30 (depressive group) had at least 1 depressive episode in adolescence. The brain structures of the groups were compared through voxel-based morphometry and analysis of cortical thickness. Individual amygdala nuclei and hippocampal subfield volumes were measured. The analysis showed larger amygdala volume, thicker subcallosal cortex and bilateral insula in the women in the HRG compared with those in the depressive group. In addition, we detected more gray matter in the left temporal pole in the HRG. The larger gray matter volume and increased cortical thickness in the key hub regions of the salience network (amygdala and insula) and structurally connected regions in the limbic network (subcallosal area and temporal pole) might prevent women in the HRG from converting to depression.

Brain imaging features in schizophrenia with co-occurring auditory verbal hallucinations and depressive symptoms-Implication for novel therapeutic strategies to alleviate the reciprocal deterioration.

BackgroundAuditory verbal hallucinations (AVHs) and depressive symptoms are highly prevalent in schizophrenia, and recent progress has been made in understanding the reciprocal deterioration of both symptoms through structural and functional brain imaging studies. To date, there is limited literature on this topic. In this review, we synthesized the recent literature on the neuroimaging features of schizophrenia patients with concurrent AVHs and depressive symptoms.MethodsA literature search was conducted with the major databases using the keywords, mainly including schizophrenia, AVHs, depression, neuropsychiatric disorders, brain imaging, and magnetic resonance imaging.ResultsThe existing studies have shown that AVHs and depressive symptoms reciprocally deteriorate in patients with schizophrenia, which has challenged the conventional treatment of the disease. Interestingly, repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) therapies have emerged as two efficacious brain stimulation treatments that can normalize the brain regions associated with the symptoms, as shown through functional and structural brain imaging studies. In light of these important findings, there is an urgent need to conduct in‐depth neuronal mechanistic studies to identify targets for stimulation therapy.ConclusionsThese new findings may elucidate the pathological mechanisms underlying schizophrenia with concurrent AVHs and depressive symptoms. Furthermore, this review has important clinical implications for developing novel therapeutic strategies to alleviate the reciprocal deterioration AVHs and depressive symptoms of schizophrenia patients.

S162. MULTI-MODAL ANALYSIS OF THE EFFECTS OF URBAN UPBRINGING ON BRAIN STRUCTURE: THE FOR2107 COHORT

BackgroundUrbanicity has been identified as a major environmental risk factor for schizophrenia as well as other major mental disorders. While initial structural brain imaging studies have pointed to medial and lateral prefrontal cortices being associated with urbanicity during childhood and adolescence, most of these studies have been limited to smaller samples and single analysis methods. The present study used the large ongoing FOR2107 multi-centre study cohort (Kircher et al., 2018) to analyse associations of urban upbringing.MethodsWe analysed a data set of n=625 healthy subjects without a current or previous psychiatric disorder (ascertained through SCID-I interviews), who underwent 3 Tesla MRI scanning, obtaining a high-resolution T1-weighted MPRAGE and a DTI scan. We subsequently also analysed a pilot samples of 42 patients with DSM-IV schizophrenia. We obtained data on urban upbringing (Lederbogen score; Lederbogen et al., 2014) for the first 15 years of life, as well as number of moves. T1 data were pre-processed using CAT12 software, using surface-based morphometric analysis of cortical thickness (CT) with 15 mm smoothing. DTI data were analysed using the TBSS approach in FSL software. We used general linear models to calculate multiple regression analyses using both linear and quadratic (non-linear) associations with urbanicity scores, followed up by analyses of correlations with number of relocations (as unspecific stress factors). Analyses of CT and DTI were each corrected for multiple comparisons using FWE.ResultsIn the healthy subject cohort we identified a significant negative linear correlation (p=0.042 FWE cluster-level; p=0.014 peak-level) between urban upbringing scores and cortical thickness (CT) in a right precuneus / posterior cingulate cluster (x/y/z=35;-88;-15), while non-linear analysis identified an additional trend in the left occipital cortex (p=0.073 FWE cluster-level; -17;-100;15). We did not find significant effects for number of relocations/moves. DTI analysis of fractional anisotropy (FA) showed a significant association (all p<0.05 FWE-corrected) for the uncinate fasciculus and inferior fronto-occipital fasciculus. CT analysis in the schizophrenia pilot cohort showed similar effects, but in a more dorsal precuneus cluster (6;-56;45) only at uncorrected levels.DiscussionOur study identified structural variation in cortical thickness in the precuneus / posterior cingulate cortex of healthy subjects, regions linked to abnormal DMN activity and stress. While the trend-level finding in schizophrenia patients was located in an adjacent cluster, our findings can be interpreted as these medial parietal lobe structure mediating this particular risk factor. Our findings argue against a more wide-spread non-specific effect, as seen in some earlier smaller studies, but points to distinct neuronal network as mediators of this particular risk. The identified brain regions are linked to stress. Unlike previous prefrontal findings, they suggest a new link to the precuneus, a central hub of the default mode network. Given that these effects were observed in clinically healthy subjects, our findings also carry implications for a better understanding of the macro-environment in adolescence.

Brain structural correlates of familial risk for mental illness: a meta-analysis of voxel-based morphometry studies in relatives of patients with psychotic or mood disorders.

Schizophrenia (SCZ), bipolar disorder (BD), and major depressive disorder (MDD) are heritable psychiatric disorders with partially overlapping genetic liability. Shared and disorder-specific neurobiological abnormalities associated with familial risk for developing mental illnesses are largely unknown. We performed a meta-analysis of structural brain imaging studies in relatives of patients with SCZ, BD, and MDD to identify overlapping and discrete brain structural correlates of familial risk for mental disorders. Search for voxel-based morphometry studies in relatives of patients with SCZ, BD, and MDD in PubMed and Embase identified 33 studies with 2292 relatives and 2052 healthy controls (HC). Seed-based d Mapping software was used to investigate global differences in gray matter volumes between relatives as a group versus HC, and between those of each psychiatric disorder and HC. As a group, relatives exhibited gray matter abnormalities in left supramarginal gyrus, right striatum, right inferior frontal gyrus, left thalamus, bilateral insula, right cerebellum, and right superior frontal gyrus, compared with HC. Decreased right cerebellar gray matter was the only abnormality common to relatives of all three conditions. Subgroup analyses showed disorder-specific gray matter abnormalities in left thalamus and bilateral insula associated with risk for SCZ, in left supramarginal gyrus and right frontal regions with risk for BD, and in right striatum with risk for MDD. While decreased gray matter in right cerebellum might be a common brain structural abnormality associated with shared risk for SCZ, BD, and MDD, regional gray matter abnormalities in neocortex, thalamus, and striatum appear to be disorder-specific.

Changes in the intracranial volume from early adulthood to the sixth decade of life: A longitudinal study

Normal brain-aging occurs at all structural levels. Excessive pathophysiological changes in the brain, beyond the normal one, are implicated in the etiology of brain disorders such as severe forms of the schizophrenia spectrum and dementia. To account for brain-aging in health and disease, it is critical to study the age-dependent trajectories of brain biomarkers at various levels and among different age groups.The intracranial volume (ICV) is a key biological marker, and changes in the ICV during the lifespan can teach us about the biology of development, aging, and gene X environment interactions. However, whether ICV changes with age in adulthood is not resolved.Applying a semi-automatic in-house-built algorithm for ICV extraction on T1w MR brain scans in the Dutch longitudinal cohort (GROUP), we measured ICV changes. Individuals between the ages of 16 and 55 years were scanned up to three consecutive times with 3.32±0.32 years between consecutive scans (N = 482, 359, 302). Using the extracted ICVs, we calculated ICV longitudinal aging-trajectories based on three analysis methods; direct calculation of ICV differences between the first and the last scan, fitting all ICV measurements of individuals to a straight line, and applying a global linear mixed model fitting. We report statistically significant increase in the ICV in adulthood until the fourth decade of life (average change +0.03%/y, or about 0.5 ml/y, at age 20), and decrease in the ICV afterward (−0.09%/y, or about −1.2 ml/y, at age 55). To account for previous cross-sectional reports of ICV changes, we analyzed the same data using a cross-sectional approach. Our cross-sectional analysis detected ICV changes consistent with the previously reported cross-sectional effect. However, the reported amount of cross-sectional changes within this age range was significantly larger than the longitudinal changes. We attribute the cross-sectional results to a generational effect.In conclusion, the human intracranial volume does not stay constant during adulthood but instead shows a small increase during young adulthood and a decrease thereafter from the fourth decade of life. The age-related changes in the longitudinalmeasure are smaller than those reported using cross-sectional approaches and unlikely to affect structural brain imaging studies correcting for intracranial volume considerably. As to the possible mechanisms involved, this awaits further study, although thickening of the meninges and skull bones have been proposed, as well as a smaller amount of brain fluids addition above the overall loss of brain tissue.

Neuroimaging Findings in Chronic Hepatitis C Virus Infection: Correlation with Neurocognitive and Neuropsychiatric Manifestations

Chronic hepatitis C virus (HCV) infection is commonly associated with neurocognitive dysfunction, altered neuropsychological performance and neuropsychiatric symptoms. Quantifiable neuropsychological changes in sustained attention, working memory, executive function, verbal learning and recall are the hallmark of HCV-associated neurocognitive disorder (HCV-AND). This constellation is at variance with the neuropsychological complex that is seen in minimal hepatic encephalopathy, which is typified by an array of alterations in psychomotor speed, selective attention and visuo-constructive function. Noncognitive symptoms, including sleep disturbances, depression, anxiety and fatigue, which are less easily quantifiable, are frequently encountered and can dominate the clinical picture and the clinical course of patients with chronic HCV infection. More recently, an increased vulnerability to Parkinson’s disease among HCV-infected patients has also been reported. The degree to which neurocognitive and neuropsychiatric changes are due to HCV replication within brain tissues or HCV-triggered peripheral immune activation remain to be determined. Without absolute evidence that clearly exonerates or indicts HCV, our understanding of the so-called “HCV brain syndrome”, relies primarily on clinical and neuropsychological assessments, although other comorbidities and substance abuse may impact on neurocognitive function, thus confounding an appropriate recognition. In recent years, a number of functional and structural brain imaging studies have been of help in recognizing possible biological markers of HCV-AND, thus providing a rationale for guiding and justifying antiviral therapy in selected cases. Here, we review clinical, neuroradiological, and therapeutic responses to interferon-based and interferon-free regimens in HCV-related cognitive and neuropsychiatric disorder.

Alcohol Intoxication and Cognition: Implications on Mechanisms and Therapeutic Strategies.

Binge alcohol drinking is highly prevalent in young adults and results in 30% deaths per year in young males. Binge alcohol drinking or acute alcohol intoxication is a risk factor for developing alcohol use disorder (AUD). Three FDA approved drugs are currently in use as therapy for AUD; however, all of them have contra-indications and limitations. Structural brain imaging studies in alcoholics have shown defects in the brain regions involved in memory, cognition and emotional processing. Positron emission tomography (PET) using radiotracers (e.g., 18FDG) and measuring brain glucose metabolism have demonstrated diagnostic and prognostic utility in evaluating patients with cognitive impairment. Using PET imaging, only a few exclusive human studies have addressed the relationship between alcohol intoxication and cognition. Those studies indicate that alcohol intoxication causes reduction in brain activity. Consistent with prior findings, a recent study by us showed that acute alcohol intoxication reduced brain activity in the cortical and subcortical regions including the temporal lobe consisting the hippocampus. Additionally, we have observed a strong correlation between reduction in metabolic activity and spatial cognition impairment in the hippocampus after binge alcohol exposure. We have also demonstrated the involvement of a stress response protein, cold inducible RNA binding protein (CIRP), as a potential mechanistic mediator in acute alcohol intoxication. In this review, we will first discuss in detail prior human PET imaging studies on alcohol intoxication as well as our recent study on acute alcohol intoxication, and review the existing literature on potential mechanisms of acute alcohol intoxication-induced cognitive impairment and therapeutic strategies to mitigate these impairments. Finally, we will highlight the importance of studying brain regions as part of a brain network in delineating the mechanism of acute alcohol intoxication-induced cognitive impairment to aid in the development of therapeutics for such indication.

Alterations in cerebellar grey matter structure and covariance networks in young people with Tourette syndrome

Tourette syndrome (TS) is a childhood-onset neurological disorder characterised by the occurrence of motor and vocal tics and the presence of premonitory sensory/urge phenomena. Functional neuroimaging studies in humans, and experimental investigations in animals, have shown that the genesis of tics in TS involve a complex interaction between cortical-striatal-thalamic-cortical brain circuits and additionally appears to involve the cerebellum. Furthermore, structural brain imaging studies have demonstrated alterations in grey matter (GM) volume in TS across a wide range of brain areas, including alterations in GM volume within the cerebellum. Until now, no study to our knowledge has yet investigated how GM structural covariance networks linked to the cerebellum may be altered in individuals with TS. In this study we employed voxel-based morphometry, and a ‘seed-to-voxel’ structural covariance network (SCN) mapping approach, to investigate alterations in GM cerebellar volume in people with TS, and alterations in cerebellar SCNs associated with TS. Data from 64 young participants was entered in the final analysis, of which 28 had TS while 36 were age-and sex-matched healthy volunteers. Using the spatially unbiased atlas template of the cerebellum and brainstem (SUIT) atlas, we found reduced GM volume in cerebellar lobule involved in higher-order cognitive functions and sensorimotor processing, in patients. In addition, we found that several areas located in frontal and cingulate cortices and sensorimotor network in addition to subcortical areas show altered structural covariance with our cerebellar seed compared to age-matched controls. These results add to the increasing evidence that cortico-basal ganglia–cerebellar interactions play an important role in tic symptomology.

Anticipatory Threat Responding: Associations With Anxiety, Development, and Brain Structure

BackgroundWhile translational theories link neurodevelopmental changes in threat learning to pathological anxiety, findings from studies in patients inconsistently support these theories. This inconsistency may reflect difficulties in studying large patient samples with wide age ranges using consistent methods. A dearth of imaging data in patients further limits translational advances. We address these gaps through a psychophysiology and structural brain imaging study in a large sample of patients across the lifespan. MethodsA total of 351 participants (8–50 years of age; 209 female subjects; 195 healthy participants and 156 medication-free, treatment-seeking patients with anxiety) completed a differential threat conditioning and extinction paradigm that has been validated in pediatric and adult populations. Skin conductance response indexed psychophysiological response to conditioned (CS+, CS−) and unconditioned threat stimuli. Structural magnetic resonance imaging data were available for 250 participants. Analyses tested anxiety and age associations with psychophysiological response in addition to associations between psychophysiology and brain structure. ResultsRegardless of age, patients and healthy comparison subjects demonstrated comparable differential threat conditioning and extinction. The magnitude of skin conductance response to both conditioned stimulus types differentiated patients from comparison subjects and covaried with dorsal prefrontal cortical thickness; structure–response associations were moderated by anxiety and age in several regions. Unconditioned responding was unrelated to anxiety and brain structure. ConclusionsRather than impaired threat learning, pathological anxiety involves heightened skin conductance response to potential but not immediately present threats; this anxiety-related potentiation of anticipatory responding also relates to variation in brain structure. These findings inform theoretical considerations by highlighting anticipatory response to potential threat in anxiety.

Interictal Hyperperfusion in the Higher Visual Cortex in Patients With Episodic Migraine.

Migraine pathophysiology is complex and probably involves cortical and subcortical alterations. Structural and functional brain imaging studies indicate alterations in the higher order visual cortex in patients with migraine. Arterial spin labeling magnetic resonance imaging (ASL-MRI) is a non-invasive imaging method for assessing changes in cerebral blood flow (CBF) in vivo. To examine if interictal CBF differs between patients with episodic migraine (EM) with or without aura and healthy controls (HC). We assessed interictal CBF using 2D pseudo-continuous ASL-MRI on a 3 Tesla Philips scanner (University Hospital Zurich, Switzerland) in EM (N=17, mean age 32.7±9.9, 13 females) and HC (N=19, mean age 31.0±9.3, 11 females). Compared to HC, EM showed exclusively hyperperfusion in the right MT+ and Cohen's d effect size was 0.99 (HC mean CBF±SD: 33.1±5.9mL/100g/minutes; EM mean CBF: 40.9±9.4mL/100g/minutes). EM with aura (N=13, MwA) revealed hyperperfusion compared to HC in the right MT+ and superior temporal gyrus. For MT, Cohen's d effect size was 1.34 (HC mean CBF±SD: 33.1±5.9mL/100g/minutes; MwA mean CBF: 43.3±8.6mL/100g/minutes). For the superior temporal gyrus, Cohen's d effect size was 1.28 (HC mean CBF±SD: 40.1±4.9mL/100g/minutes; MwA mean CBF: 47.4±6.4mL/100g/minutes). In EM, anxiety was positively associated with CBF in the parietal operculum and angular gyrus. Our results suggest that extrastriate brain regions probably involved in cortical spreading depression are associated with CBF changes in the interictal state. We conclude that ASL-MRI is a sensitive method to identify local neuro-functional abnormalities in CBF in patients with EM in the interictal state.

Psychoradiological investigations of gray matter alterations in patients with anorexia nervosa

Anorexia nervosa (AN) is a severe psychiatric disorder with high mortality. The underlying neurobiological mechanisms are not well understood, and high-resolution structural magnetic resonance brain imaging studies have given inconsistent results. Here we aimed to psychoradiologically define the most prominent and replicable abnormalities of gray matter volume (GMV) in AN patients, and to examine their relationship to demographics and clinical characteristics, by means of a new coordinate-based meta-analytic technique called seed-based d mapping (SDM). In a pooled analysis of all AN patients we identified decreased GMV in the bilateral median cingulate cortices and posterior cingulate cortices extending to the bilateral precuneus, and the supplementary motor area. In subgroup analysis we found an additional decreased GMV in the right fusiform in adult AN, and a decreased GMV in the left amygdala and left anterior cingulate cortex in AN patients without comorbidity (pure AN). Thus, the most consistent GMV alterations in AN patients are in the default mode network and the sensorimotor network. These psychoradiological findings of the brain abnormalities might underpin the neuropathophysiology in AN.