Longitudinal mapping of cortical thickness and clinical outcome in children and adolescents with attention-deficit/hyperactivity disorder

CONTEXT: Data from a previous prospective study of lobar volumes in children with attention-deficit/hyperactivity disorder (ADHD) are reexamined using a measure of cortical thickness. OBJECTIVE: To determine whether regional differences in cortical thickness or cortical changes across time characterize ADHD and predict or reflect its clinical outcome. DESIGN, SETTING, AND PARTICIPANTS: Longitudinal study of 163 children with ADHD (mean age at entry, 8.9 years) and 166 controls recruited mainly from a local community in Maryland. Participants were assessed with magnetic resonance imaging. Ninety-seven patients with ADHD (60%) had 2 or more images and baseline and follow-up clinical evaluations (mean follow-up, 5.7 years). MAIN OUTCOME MEASURES: Cortical thickness across the cerebrum. Patients with ADHD were divided into better and worse outcome groups on the basis of a mean split in scores on the Children's Global Assessment Scale and persistence/remission of DSM-IV-defined ADHD. RESULTS: Children with ADHD had global thinning of the cortex (mean reduction, -0.09 mm; P=.02), most prominently in the medial and superior prefrontal and precentral regions. Children with worse clinical outcome had a thinner left medial prefrontal cortex at baseline than the better outcome group (-0.38 mm; P=.003) and controls (-0.25 mm; P=.002). Cortical thickness developmental trajectories did not differ significantly between the ADHD and control groups throughout except in the right parietal cortex, where trajectories converged. This normalization of cortical thickness occurred only in the better outcome group. CONCLUSIONS: Children with ADHD show relative cortical thinning in regions important for attentional control. Children with a worse outcome have "fixed" thinning of the left medial prefrontal cortex, which may compromise the anterior attentional network and encumber clinical improvement. Right parietal cortex thickness normalization in patients with a better outcome may represent compensatory cortical change.     

DTNBP1 is associated with imaging phenotypes in schizophrenia

Dystrobrevin binding protein 1 (DTNBP1) has been identified as putative schizophrenia susceptibility gene, but it remains unknown whether polymorphisms relate to altered cerebral structure. We examined relationships between a previously implicated DTNBP1 risk variant [P1578] and global and segmented brain tissue volumes and regional cortical thickness in schizophrenia (n = 62; 24 risk carriers) and healthy subjects (n = 42; 11 risk carriers), across ethnic groups and within Caucasians. Schizophrenia patients showed similar brain volumes, but significantly reduced brain‐size adjusted gray matter and CSF volumes and cortical thinning in a widespread neocortical distribution compared to controls. DTNBP1 risk was found associated with reduced brain volume, but not with tissue sub‐compartments. Cortical thickness, which was weakly associated with brain size, showed regional variations in association with genetic risk, although effects were dominated by highly significant genotype by diagnosis interactions over broad areas of cortex. Risk status was found associated with regional cortical thinning in patients, particularly in temporal networks, but with thickness increases in controls. DTNBP1 effects for brain volume and cortical thickness appear driven by different neurobiological processes. Smaller brain volumes observed in risk carriers may relate to previously reported DTNBP1/cognitive function relationships irrespective of diagnosis. Regional cortical thinning in patient, but not in control risk carriers, may suggest that DTNBP1 interacts with other schizophrenia‐related risk factors to affect laminar thickness. Alternatively, DTNBP1 may influence neural processes for which individuals with thicker cortex are less vulnerable. Although DTNBP1 relates to cortical thinning in schizophrenia, morphological changes in the disorder are influenced by additional genetic and/or environmental factors. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.     

Cortical surface anatomy in pediatric patients with generalized anxiety disorder

BackgroundIt is established that pediatric patients with generalized anxiety disorder (GAD) exhibit functional abnormalities and altered gray matter volumes in neural structures that subserve emotional processing, yet there are no data regarding the surface anatomy of the cerebral cortex in youth with GAD.MethodsUsing an automated surface-based approach (FreeSurfer), cortical thickness was assessed node-by-node over the entire cerebral cortex in adolescents with GAD and no co-occurring major depressive disorder (n = 13) and healthy subjects (n = 19).ResultsCompared with healthy adolescents, youth with GAD exhibited increased cortical thickness in the right inferolateral and ventromedial prefrontal cortex (i.e., inferior frontal gyrus), the left inferior and middle temporal cortex as well as the right lateral occipital cortex. No relationships were observed between cortical thickness and the severity of anxiety symptoms in the significant regions that were identified in the vertex-wise analysis.ConclusionsThese findings suggest that, in adolescents with GAD, abnormalities in cortical thickness are present in an ensemble of regions responsible for fear learning, fear extinction, reflective functioning (e.g., mentalization), and regulation of the amygdala.     

Regional thinning of the cerebral cortex in schizophrenia: effects of diagnosis, age and antipsychotic medication

Morphological abnormalities of the cerebral cortex have been reported in a number of MRI-studies in schizophrenia. Uncertainty remains regarding cause, mechanism and progression of the alterations. It has been suggested that antipsychotic medication reduces total gray matter volumes, but results are inconsistent. In the present study differences in regional cortical thickness between 96 patients with a DSM-IV diagnosis of schizophrenia (n=81) or schizoaffective disorder (n=15) and 107 healthy subjects (mean age 42 years, range 17-57 years) were investigated using MRI and computer image analysis. Cortical thickness was estimated as the shortest distance between the gray/white matter border and the pial surface at numerous points across the entire cortical mantle. The influence of age and antipsychotic medication on variation in global and regional cortical thickness was explored. Thinner cortex among patients than controls was found in prefrontal and temporal regions of both hemispheres, while parietal and occipital regions were relatively spared. Some hemispheric specificity was noted, as regions of the prefrontal cortex were more affected in the right hemisphere, and regions of the temporal cortex in the left hemisphere. No significant interaction effect of age and diagnostic group on variation in cortical thickness was demonstrated. Among patients, dose or type of antipsychotic medication did not affect variation in cortical thickness. The results from this hitherto largest study on the topic show that prefrontal and temporal cortical thinning in patients with schizophrenia compared to controls is as pronounced in older as in younger subjects. The lack of significant influence from antipsychotic medication supports that regional cortical thinning is an inherent feature of the neurobiological disease process in schizophrenia.     

Reduced thickness of anterior cingulate cortex in obsessive-compulsive disorder

IntroductionObsessive-compulsive disorder (OCD) is characterized by a pattern of repetitive, intrusive thoughts and behaviours that patients do not want to but feel they have to perform. Functional brain imaging revealed dysfunctional pathways in OCD involving the anterior cingulate cortex (ACC), orbitofrontal cortex (OFC), and basal ganglia. Structural alterations in OCD have been discussed but analysis tools focussing on specific morphometric aspects such as cortical thickness have rarely been employed.MethodsWe acquired MRI scans from 101 OCD patients and 95 healthy control subjects. FreeSurfer analysis software was employed to model the individual grey–white and pial surfaces to compute cortical thickness as our target measure.ResultsRelative to controls, OCD patients demonstrate cortical thinning in dorsal and subgenual ACC (false discovery rate corrected at p < .001), as well as in several other regions within the fronto-parietal network (false discovery rate corrected at p < .05). Cortical thickness could not be predicted in whole brain analyses from symptom state, but there was a modest correlation of left dorsal ACC thickness with the obsession subscore of the Yale-Brown Obsessive-Compulsive Scale as well as with the Beck Depression Inventory score.ConclusionsThe findings confirm and extend previous reports showing that OCD is associated with morphometric alterations. The location of the most robust cortical thinning in ACC regions matches the previously reported topography of functional alterations at resting state and during cognitive task execution.     

Regional cerebral cortical thinning in bipolar disorder

OBJECTIVE: This study was conducted to explore differences in cortical thickness between subjects with bipolar disorder and healthy comparison subjects using cortical surface-based analysis. METHODS: Brain magnetic resonance images were acquired from 25 subjects with bipolar disorder and 21 healthy comparison subjects. Cortical surface-based analysis was conducted using the Freesurfer application. Group differences in cortical thickness, defined by the distance from gray/white boundary to the pial surface, were assessed using statistical difference maps. RESULTS: Subjects with bipolar disorder exhibited significantly decreased cortical thickness in left cingulate cortex, left middle frontal cortex, left middle occipital cortex, right medial frontal cortex, right angular cortex, right fusiform cortex and bilateral postcentral cortices, relative to healthy comparison subjects (all p < 0.001). Duration of illness in bipolar subjects was inversely correlated with the cortical thickness of the left middle frontal cortex. CONCLUSIONS: Cortical thinning was present in multiple prefrontal cortices in bipolar disorder. There was also cortical thinning in sensory and sensory association cortices, which has not been reported in previous studies using region-of-interest or voxel-based morphometry methods. Cortical thinning observed in the current study may be related to impairment of emotional, cognitive, and sensory processing in bipolar disorder but longitudinal studies will be necessary to test this hypothesis.     

Abnormal cerebral cortex structure in children with ADHD

Objective:

Examination of cerebral cortical structure in children with Attention‐Deficit/Hyperactivity Disorder (ADHD) has thus far been principally limited to volume measures. In the current study, an automated surface‐based analysis technique was used to examine the ADHD‐associated differences in additional morphologic features of cerebral cortical gray matter structure, including surface area, thickness, and cortical folding.

Methods:

MPRAGE images were acquired from 21 children with ADHD (9 girls) and 35 typically developing controls (15 girls), aged 8–12 years. Statistical difference maps were used to compare mean cortical thickness between groups along the cortical surface. Cortical volume, surface area, mean thickness, and cortical folding were measured within regions of interest, including the right/left hemispheres, frontal, temporal, parietal, and occipital lobes within each hemisphere, and sub‐lobar regions.

Results:

Children with ADHD showed a decrease in total cerebral volume and total cortical volume of over 7 and 8%, respectively; volume reduction was observed throughout the cortex, with significant reduction in all four lobes bilaterally. The ADHD group also showed a decrease in surface area of over 7% bilaterally, and a significant decrease in cortical folding bilaterally. No significant differences in cortical thickness were detected.

Conclusions:

Results from the present study reveal that ADHD is associated with decreased cortical volume, surface area, and folding throughout the cerebral cortex. The findings suggest that decreased cortical folding is a key morphologic feature associated with ADHD. This would be consistent with onset early in neural development and could help to identify neurodevelopmental mechanisms that contribute to ADHD. Hum Brain Mapp 2009. © 2007 Wiley‐Liss, Inc.     

Cortical Morphometric Abnormality and Its Association with Working Memory in Children with Attention-Deficit/Hyperactivity Disorder

ObjectiveAttention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder in children and adolescents. The present study investigated the cortical morphology features and their relationship with working memory (WM). Methods In the present study, a total of 36 medication naïve children with ADHD (aged from 8 to 15 years) and 36 age- and gender-matched healthy control (HC) children were included. The digit span test was used to evaluate WM. The magnetic resonance imaging (MRI) was used to examine the characteristics of cortical morphology. Firstly, we compared the cortical morphology features between two groups to identify the potential structural alterations of cortical volume, surface, thickness, and curvature in children with ADHD. Then, the correlation between the brain structural abnormalities and WM was further explored in children with ADHD. Results Compared with the HC children, the children with ADHD showed reduced cortical volumes in the left lateral superior temporal gyrus (STG) (p=6.67×10^-6) and left anterior cingulate cortex (ACC) (p=3.88×10^-6). In addition, the cortical volume of left lateral STG was positively correlated with WM (r=0.36, p=0.029). Conclusion Though preliminary, these findings suggest that the reduced cortical volumes of left lateral STG may contribute to the pathogenesis of ADHD and correlate with WM in children with ADHD.     

Cognitive impairment in progressive supranuclear palsy-Richardson’s syndrome is related to white matter damage

IntroductionBeside motor symptoms, patients with progressive supranuclear palsy syndrome (PSPs) commonly present cognitive and behavioral disorders. In this study we aimed to assess the structural brain correlates of cognitive impairment in PSPs.MethodsWe enrolled 23 patients with probable PSP Richardson's syndrome and 15 matched healthy controls. Patients underwent an extensive clinical and neuropsychological evaluation. Cortical thickness measures and diffusion tensor metrics of white matter tracts were obtained. Random forest analysis was used to identify the strongest MRI predictors of cognitive impairment in PSPs at an individual patient level.ResultsPSPs patients were in a moderate stage of the disease showing mild cognitive deficits with prominent executive dysfunction. Relative to controls, PSPs patients had a focal, bilateral cortical thinning mainly located in the prefrontal/precentral cortex and temporal pole. PSPs patients also showed a distributed white matter damage involving the main tracts including the superior cerebellar peduncle, corpus callosum, corticospinal tract, and extramotor tracts, such as the inferior fronto-occipital, superior longitudinal and uncinate fasciculi, and cingulum, bilaterally. Regional cortical thinning measures did not relate with cognitive features, while white matter damage showed a significant impact on cognitive impairment (r values ranging from −0.80 to 0.74).ConclusionsPSPs patients show both focal cortical thinning in dorsolateral anterior regions and a distributed white matter damage involving the main motor and extramotor tracts. White matter measures are highly associated with cognitive deficits. Diffusion tensor MRI metrics are likely to be the most sensitive markers of extramotor deficits in PSPs.     

Investigating possible subtypes of schizophrenia patients and controls based on brain cortical thickness

Schizophrenia is a heterogeneous disease in which different dimensions could be associated with localized subtypes in cortical thickness of the brain. Subtypes in data that includes patients and controls could be associated with patient/control could associate with patient/control groupings. Testing for subtypes provides a non-parametric investigation of group differences. Cortical thickness maps, generated from magnetic resonance images of 96 patients with schizophrenia and 106 controls, were co-registered and corrected for age-related thinning. At multiple map locations, the number of (sub)types best explaining cortical thickness in the patients, the controls, and both combined was determined. Grey matter volumes of selected regions were measured. Both patients and controls, considered independently, were predominantly homogeneous in cortical thickness. The few bimodal regions were similar in both groups. The combined subjects' cortical thickness was bimodal over 34% of the cortical mantle and otherwise unimodal. Further probing of these bimodal regions showed that subjects tending to belong to thinner modes were significantly more likely to be patients, and grey matter volumes of most bimodal regions were significantly smaller in patients. The study found no subtypes specific to patients. It suggested, however, that associations between abnormally thin cortex and schizophrenia are more widespread than shown by previously published results based on significance testing.     

Regionally localized thinning of the cerebral cortex in schizophrenia

BACKGROUND: Schizophrenia is characterized by small reductions in cortical gray matter volume, particularly in the temporal and prefrontal cortices. The question of whether cortical thickness is reduced in schizophrenia has not been addressed using magnetic resonance imaging (MRI) techniques. Our objectives were to test the hypothesis that cortical thinning in patients with schizophrenia (relative to control subjects) is greater in temporal and prefrontal regions of interest (ROIs) than in control ROIs (superior parietal, calcarine, postcentral, central, and precentral cortices), and to obtain an unbiased estimate of the distribution of cortical thinning in patients (relative to controls) by constructing mean and statistical cortical thickness difference maps. METHODS: Participants included 33 right-handed outpatients receiving medication and meeting DSM-IV criteria for schizophrenia and 32 healthy volunteers, matched on age and parental socioeconomic status. After high-resolution MRI scans, models of the gray-white and pial surfaces were generated for each individual's cortex, and the distance between these 2 surfaces was used to compute cortical thickness. A surface-based averaging technique that aligned the main cortical folds across individuals allowed between-group comparisons of thickness within ROIs, and at multiple, uniformly sampled loci across the cortical ribbon. RESULTS: Relative to controls, patients showed greater cortical thinning in temporal-prefrontal ROIs than in control ROIs, as revealed by a significant (P<.009) interaction between group and region type. Cortical thickness difference maps revealed significant (at P<.05, corrected) thinning within the orbitofrontal cortices bilaterally; the inferior frontal, inferior temporal, and occipitotemporal cortices on the left; and within the medial temporal and medial frontal cortices on the right. Superior parietal and primary somatosensory and motor cortices were relatively spared, even at subthreshold significance levels. CONCLUSIONS: Patients with chronic schizophrenia showed widespread cortical thinning that particularly affected the prefrontal and temporal cortices. This thinning might reflect underlying neuropathological abnormalities in cortical structure.     

Voxel-based morphometry analysis reveals frontal brain differences in participants with ADHD and their unaffected siblings

BackgroundData on structural brain alterations in patients with attention-deficit/hyperactivity disorder (ADHD) have been inconsistent. Both ADHD and brain volumes have a strong genetic loading, but whether brain alterations in patients with ADHD are familial has been underexplored. We aimed to detect structural brain alterations in adolescents and young adults with ADHD compared with healthy controls. We examined whether these alterations were also found in their unaffected siblings, using a uniquely large sample.MethodsWe performed voxel-based morphometry analyses on MRI scans of patients with ADHD, their unaffected siblings and typically developing controls. We identified brain areas that differed between participants with ADHD and controls and investigated whether these areas were different in unaffected siblings. Influences of medication use, age, sex and IQ were considered.ResultsOur sample included 307 patients with ADHD, 169 unaffected siblings and 196 typically developing controls (mean age 17.2 [range 8–30] yr). Compared with controls, participants with ADHD had significantly smaller grey matter volume in 5 clusters located in the precentral gyrus, medial and orbitofrontal cortex, and (para)cingulate cortices. Unaffected siblings showed intermediate volumes significantly different from controls in 4 of these clusters (all except the precentral gyrus). Medication use, age, sex and IQ did not have an undue influence on the results.LimitationsOur sample was heterogeneous, most participants with ADHD were taking medication, and the comparison was cross-sectional.ConclusionBrain areas involved in decision making, motivation, cognitive control and motor functioning were smaller in participants with ADHD than in controls. Investigation of unaffected siblings indicated familiality of 4 of the structural brain differences, supporting their potential in molecular genetic analyses in ADHD research.     

Topographic pattern of cortical thinning with consideration of motor laterality in Parkinson disease

BackgroundThe asymmetry of Parkinson's disease (PD) may contribute to the unilateral appearance of parkinsonism, as well as its cerebral morphological changes. However, previous studies have not considered that cerebral involvement would probably be asymmetric. Our study aimed to identify whether one-sided symptom dominance has an influence on cortical thinning patterns in early-stage, non-demented PD patients from cortical thickness analyses and cortical thinning patterns are associated with motor functions.MethodsWe used cortical thickness analysis in 64 non-demented right-handed subjects: 21 PD patients with left-sided disease onset (LPD), 21 PD patients with right-sided disease onset (RPD) and 22 control subjects. We modeled local cortical thickness as a linear association with each motor symptom.ResultsWe identified three clusters exhibiting significant cortical thinning (p < 0.01 RFT corrected) in the LPD group compared with the control group: a cluster including the right primary sensory, motor cortex and paracentral lobule, as well as another two clusters in bilateral parahippocampal gyri. In the RPD group, there was only one cluster that exhibited significant cortical thinning compared with the control group, located in the left lingual gyrus. There were no significant correlations between cortical thinning clusters and motor severity, any of the motor subscales including tremor, rigidity, bradykinesia and axial impairment.ConclusionsOur right-handed PD population revealed that significant thinning of motor-related cortical areas in contralateral hemisphere to symptomatic side in LPD, but not in RPD group. Our results support that neuroprotective effect of enhanced physical activity by handedness on contralateral motor cortex.     

Reduced right frontal cortical thickness in children, adolescents and adults with ADHD and its correlation to clinical variables: A cross-sectional study

Objective

Some longitudinal magnetic resonance imaging (MRI) studies have shown reduced volume or cortical thickness (CT) in the frontal cortices of individuals with attention-deficit/hyperactivity disorder (ADHD). These studies indicated that the aforementioned anatomical abnormalities disappear during adolescence. In contrast, cross-sectional studies on adults with ADHD have shown anatomical abnormalities in the frontal lobe region. It is not known whether the anatomical abnormalities in ADHD are a delay or a deviation in the encephalic maturation. The aim of this study was to compare CT in the frontal lobe of children, adolescents and adults of both genders presenting ADHD with that in corresponding healthy controls and to explore its relationship with the severity of the illness.

Method

An MRI scan study was performed on never-medicated ADHD patients. Twenty-one children (6–10 year-olds), twenty adolescents (14–17 year-olds) and twenty adults (25–35 year-olds) were matched with healthy controls according to age and sex. CT measurements were performed using the Freesurfer image analysis suite.

Results

The data showed regions in the right superior frontal gyrus where CT was reduced in children, adolescents and adults with ADHD in contrast to their respective healthy controls. The CT of these regions correlated with the severity of the illness.

Conclusions

In subjects with ADHD, there is a thinning of the cortical surface in the right frontal lobe, which is present in the children, adolescents and in adults.     

Brief International Cognitive Assessment for Multiple Sclerosis scores are associated with the cortical thickness of specific cortical areas in relapsing-remitting patients

BackgroundCognitive impairment is frequent and disabling in multiple sclerosis (MS). The Brief International Cognitive Assessment in MS (BICAMS) is a recent short battery usable in clinical practice for cognitive evaluation of MS patients.ObjectiveTo find cortical areas or brain volumes on magnetic resonance imaging (MRI) structural sequences associated with BICAMS scores in MS.MethodsIn this cross-sectional single-center study (NCT 03656055, September 4, 2018), 96 relapsing remitting-MS patients under natalizumab and without recent clinical or radiological inflammation were included. Patients underwent brain MRI and the three BICAMS tests, evaluating information processing speed (SDMT), visuo-spatial memory (BVMT-R), and verbal memory (FVLT).ResultsCortical thickness in the left frontal superior and the right precentral gyri was associated with BVMT-R scores whereas cortical thickness in the left Broca's area and the right superior temporal gyrus was associated with FVLT scores. We observed associations between white matter inflammatory lesions connected to these cortical regions and BICAMS subscores.ConclusionsBICAMS scores are associated with specific cortical areas, the cognitive domain matching the known functions of the cortical area. Specific cognitive impairments in MS may be associated with specific cortical regions, themselves influenced by white matter inflammatory lesions and demographical parameters (age, sex, education level).     

Anterior cingulate, gyrus rectus, and orbitofrontal abnormalities in elderly depressed patients: an MRI-based parcellation of the prefrontal cortex

OBJECTIVE: To examine structural abnormalities in subregions of the prefrontal cortex in elderly patients with depression, the authors explored differences in gray matter, white matter, and CSF volumes by applying a parcellation method based on magnetic resonance imaging (MRI). METHOD: Twenty-four elderly patients with major depression and 19 group-matched comparison subjects were studied with high-resolution MRI. Cortical surface extraction, tissue segmentation, and cortical parcellation methods were applied to obtain volume measures of gray matter, white matter, and CSF in seven prefrontal subregions: the anterior cingulate, gyrus rectus, orbitofrontal cortex, precentral gyrus, superior frontal cortex, middle frontal cortex, and inferior frontal cortex. RESULTS: Highly significant bilateral volume reductions in gray matter were observed in the anterior cingulate, the gyrus rectus, and the orbitofrontal cortex. Depressed patients also exhibited significant bilateral white matter volume reductions and significant CSF volume increases in the anterior cingulate and the gyrus rectus. Finally, the depressed group showed significant CSF volume reductions in the orbitofrontal cortex relative to the comparison subjects. None of the other regions examined revealed significant structural abnormalities. CONCLUSIONS: The prominent bilateral gray matter deficits in the anterior cingulate and the gyrus rectus as well as the orbitofrontal cortex may reflect disease-specific modifications of elderly depression. The differential pattern of abnormalities detected in the white matter and CSF compartments imply that distinct etiopathological mechanisms might underlie the structural cortical changes in these regions.     

Topographic distribution of cortical thinning in subtypes of multiple system atrophy

Background and purposeDespite the predominant degeneration of subcortical structures, recent studies have suggested the evidence of cortical involvement in multiple system atrophy (MSA). This study aimed to identify the different topographic pattern of cortical thinning in MSA according to clinical subtypes, and the association of cortical thinning with cerebellar atrophy and other disease related metrics.Materials and methodsWe used cortical thickness analysis in 53 non-demented probable MSA patients (29 with MSA-C, 24 with MSA-P) and 35 healthy subjects and modeled local cortical thickness as a linear association with cerebellar volume and disease related metrics including age, disease duration, cognition and disease severity.ResultsWe found five clusters (left ventromedial prefrontal, bilateral ventrolateral prefrontal cortex, right parahippocampal and lingual gyrus) exhibiting significant cortical thinning in MSA-C and two clusters (right primary sensory motor and left ventromedial prefrontal cortex) exhibiting a thinning tendency in MSA-P compared with the control group. In correlation analysis, we identified no cluster exhibiting a significant correlation with cerebellar atrophy in both of the MSA groups. However, cortical thickness in right parahippocampalgyrus and left ventrolateral prefrontal cortex showed significant negative correlation with International Cooperative Ataxia Rating Scale subscore of speech disorder in MSA-C group.ConclusionsWe identified different topographic distributions of cortical thinning in MSA subtypes. Our study suggests that cortical thinning of MSA occurs independently of cerebellar atrophy as a primary disease process rather than secondary deafferentation.     

Disrupted Prefrontal Interhemispheric Structural Coupling in Schizophrenia Related to Working Memory Performance

Background: Prominent regional cortical thickness reductions have been shown in schizophrenia. In contrast, little is known regarding alterations of structural coupling between regions in schizophrenia and how these alterations may be related to cognitive impairments in this disorder. Methods: T1-weighted magnetic resonance images were acquired in 54 patients with schizophrenia and 68 healthy control subjects aged 18–55 years. Cortical thickness was compared between groups using a vertex-wise approach. To assess structural coupling, seeds were selected within regions of reduced thickness, and brain-wide cortical thickness correlations were compared between groups. The relationships between identified patterns of circuit structure disruption and cognitive task performance were then explored. Results: Prominent cortical thickness reductions were found in patients compared with controls at a 5% false discovery rate in a predominantly frontal and temporal pattern. Correlations of the left dorsolateral prefrontal cortex (DLPFC) with right prefrontal regions were significantly different in patients and controls. The difference remained significant in a subset of 20 first-episode patients. Participants with stronger frontal interhemispheric thickness correlations had poorer working memory performance. Conclusions: We identified structural impairment in a left-right DLPFC circuit in patients with schizophrenia independent of illness stage or medication exposure. The relationship between left-right DLPFC thickness correlations and working memory performance implicates prefrontal interhemispheric circuit impairment as a vulnerability pathway for poor working memory performance. Our findings could guide the development of novel therapeutic interventions aimed at improving working memory performance in patients with schizophrenia.Key words: dorsolateral prefrontal cortex, MRI, cortical thickness, structural coupling     

Cortical Thickness Reduction in Individuals at Ultra-High-Risk for Psychosis

Although schizophrenia is characterized by gray matter (GM) abnormalities, particularly in the prefrontal and temporal cortices, it is unclear whether cerebral cortical GM is abnormal in individuals at ultra-high-risk (UHR) for psychosis. We addressed this issue by studying cortical thickness in this group with magnetic resonance imaging (MRI). We measured cortical thickness of 29 individuals with no family history of psychosis at UHR, 31 patients with schizophrenia, and 29 healthy matched control subjects using automated surface-based analysis of structural MRI data. Hemispheric mean and regional cortical thickness were significantly different according to the stage of the disease. Significant cortical differences across these 3 groups were found in the distributed area of cerebral cortices. UHR group showed significant cortical thinning in the prefrontal cortex, anterior cingulate cortex, inferior parietal cortex, parahippocampal cortex, and superior temporal gyrus compared with healthy control subjects. Significant cortical thinning in schizophrenia group relative to UHR group was found in all the regions described above in addition with posterior cingulate cortex, insular cortex, and precentral cortex. These changes were more pronounced in the schizophrenia group compared with the control subjects. These findings suggest that UHR is associated with cortical thinning in regions that correspond to the structural abnormalities found in schizophrenia. These structural abnormalities might reflect functional decline at the prodromal stage of schizophrenia, and there may be progressive thinning of GM cortex over time.     

Smaller prefrontal and premotor volumes in boys with attention-deficit/hyperactivity disorder.

BACKGROUND: Anatomic magnetic resonance imaging (MRI) studies of attention-deficit/hyperactivity disorder (ADHD) have been limited by use of callosal rather than sulcal/gyral landmarks in defining cerebral lobes and functionally relevant sublobar regions (e.g., prefrontal cortex). We present an investigation of cerebral volumes in ADHD using a Talairach-based approach that uses cortical landmarks to define functionally relevant regions. METHODS: Volumes were compared between groups of 12 boys with ADHD and 12 age- and gender-matched control subjects, using a series of multiple analyses of variance. RESULTS: Boys with ADHD had (on average) 8.3% smaller total cerebral volumes. Significant reductions in lobar volumes were seen only for the frontal lobes. Within the frontal lobes, a reduction was seen in both gray and white matter volumes, with some evidence suggesting lateralization of these findings: reduction in frontal white matter volume was specific to the left hemisphere; there was a bilateral reduction in frontal gray matter volume but more so in the right hemisphere. Subparcellation of the frontal lobe revealed smaller prefrontal, premotor, and deep white matter volumes. CONCLUSIONS: Findings suggest that ADHD is associated with decreased frontal lobe gray and white matter volumes. More than one subdivision of the frontal lobes appears to be reduced in volume, suggesting that the clinical picture of ADHD encompasses dysfunctions attributable to anomalous development of both premotor and prefrontal cortices.