Total Cortical Gray Matter Volume Research Articles

Sex Differences in Human Brain Structure at Birth

BackgroundSex differences in human brain anatomy have been well-documented, though remain significantly underexplored during early development. The neonatal period is a critical stage for brain development and can provide key insights into the role that prenatal and early postnatal factors play in shaping sex differences in the brain.MethodsHere, we assessed on-average sex differences in global and regional brain volumes in 514 newborns aged 0–28 days (236 birth-assigned females and 278 birth-assigned males) using data from the developing Human Connectome Project. We also assessed sex-by-age interactions to investigate sex differences in early postnatal brain development.ResultsOn average, males had significantly larger intracranial and total brain volumes, even after controlling for birth weight. After controlling for total brain volume, females showed significantly greater total cortical gray matter volumes, whilst males showed greater total white matter volumes. After controlling for total brain volume in regional comparisons, females had significantly increased white matter volumes in the corpus callosum and increased gray matter volumes in the bilateral parahippocampal gyri (posterior parts), left anterior cingulate gyrus, bilateral parietal lobes, and left caudate nucleus. Males had significantly increased gray matter volumes in the right medial and inferior temporal gyrus (posterior part) and right subthalamic nucleus. Effect sizes ranged from small for regional comparisons to large for global comparisons. Significant sex-by-age interactions were noted in the left anterior cingulate gyrus and left superior temporal gyrus (posterior parts).ConclusionsOur findings demonstrate that sex differences in brain structure are already present at birth and remain comparatively stable during early postnatal development, highlighting an important role of prenatal factors in shaping sex differences in the brain.

Sex dimorphic cortical brain volumes associated with antisocial behavior in young adults.

Although sex differences in antisocial behavior are well-documented, the extent to which neuroanatomical differences are related to sex differences in antisocial behavior is unclear. The inconsistent results from different clinical populations exhibiting antisocial behaviors are mainly due to the heterogeneity in etiologies, comorbidity inequality, and small sample size, especially in females. The study aimed to find sexual dimorphic brain regions associated with individual differences in antisocial behavior while avoiding the issues of heterogeneity and sample size. We collected structural neuroimaging data from 281 college students (131 males, 150 females) and analyzed the data using voxel-based morphometry. The gray matter volume in three brain regions correlates with self-reported antisocial behavior in males and females differently: the posterior superior temporal sulcus, middle temporal gyrus, and precuneus. The findings have controlled for the total cortical gray matter volume, age, IQ, and socioeconomic status. Additionally, we found a common neural substrate of antisocial behavior in both males and females, extending from the anterior temporal lobe to the insula. This is the first neuroanatomical evidence from a large non-clinical sample of young adults. The study suggests that differences in males and females in reading social cues, understanding intentions and emotions, and responding to conflicts may contribute to the modulation of brain morphometry concerning antisocial behavior.

Polygenic risk scores and brain structures both contribute to externalizing behavior in childhood - A study in the Adolescent Brain and Cognitive Development (ABCD) cohort

IntroductionExternalizing behaviors are defined as behaviors violating social norms and can be harmful to self and others. Predicting the escalation of externalizing behaviors in children would allow for early interventions to prevent the occurrence of antisocial and criminal acts. Externalizing behaviors are heritable traits, and have been associated with structures of the brain. Brain structure, in turn, is also influenced by genetics. Here, we investigated the association of genetic and brain structural variation with externalizing behaviors in late childhood, and we assessed potential mediating effects. MethodsData was collected for 11,878 children aged 9–10 years old from the Adolescent Brain Cognitive Development (ABCD) cohort. We extracted data on externalizing behaviors measured by the parent-reported Child Behavior Checklist (CBCL), brain volumes and white matter integrity measured by magnetic resonance imaging (MRI), and polygenic risk scores (PRS) for (i) antisocial behaviors, (ii) attention-deficit/hyperactivity disorder comorbid with disruptive behavior disorder (ADHD ​+ ​DBD), (iii) irritability, and (iv) traits related to self-regulation & addiction. We examined the associations between brain structures, PRS, and externalizing behavior, and to what extent brain structures mediate the association between PRS and externalizing behavior. Phenotypic associations between brain structures and externalizing behaviors were validated in an independent cohort of 150 adolescents aged 12–21 years enriched for individuals with antisocial behavior. ResultsIncreasing levels of externalizing behaviors were associated with reduced total brain and focal gray matter volumes, but not with white matter integrity. These results could not be validated in the independent cohort, except for a good correlation of several effect sizes between the cohorts. Higher PRS for externalizing behaviors were associated with lower cortical gray matter volume, larger subcortical gray matter volume, larger white matter volume, and reduced global white matter fractional anisotropy. Genetic and brain structural variation, combined with sociodemographic factors, explained up to 7% of variation in externalizing behaviors in late childhood; brain structures and PRS each explained up to ∼0.5% of variation. A multivariate model with all sociodemographic factors, brain structures and PRS combined explained up to 11.9% (+5%). Total cortical gray matter volume mediated the association between PRS for ADHD ​+ ​DBD and externalizing behavior in late childhood. However, a large proportion of individual variation in externalizing behavior remained unidentified (∼90%). Brain function and interaction effects with the environment are surmised as potential sources of additional variation.

Subcortical structures associated with childhood trauma and perceived stress in schizophrenia.

Childhood trauma influences the clinical features of schizophrenia. In this study, we examined how childhood trauma and perceived stress are associated with clinical manifestations and subcortical gray matter volumes (GMVs) in patients with schizophrenia. We recruited 127 patients with schizophrenia and 83 healthy controls for assessment of early childhood trauma, perceived stress, and clinical symptoms. With structural brain imaging, we identified the GMVs of subcortical structures and examined the relationships between childhood trauma, perceived stress, clinical symptoms, and subcortical GMVs. Compared to controls, patients with schizophrenia showed higher levels of childhood trauma and perceived stress. Patients with schizophrenia showed significantly smaller amygdala and hippocampus GMVs as well as total cortical GMVs than age-matched controls. Childhood trauma score was significantly correlated with the severity of clinical symptoms, depression, perceived stress, and amygdala GMVs. Perceived stress was significantly correlated with clinical symptoms, depression, and hippocampus and amygdala GMVs. Further, the association between childhood trauma (emotional neglect) and stress coping ability was mediated by right amygdala GMV in patients with schizophrenia. Patients with schizophrenia had more exposure to early-life trauma and poorer stress coping. Both childhood trauma and perceived stress were associated with smaller amygdala volumes. The relationship between early-life trauma and perceived stress was mediated by right amygdala GMV in patients with schizophrenia. These findings together suggest the long-term effects of childhood trauma on perceived stress and the subcortical volumetric correlates of the effects in schizophrenia.

Impact of Multidomain Lifestyle Intervention on Cerebral Cortical Thickness and Serum Brain-Derived Neurotrophic Factor: the SUPERBRAIN Exploratory Sub-study

In the SoUth Korean study to PrEvent cognitive impaiRment and protect BRAIN health through lifestyle intervention in at-risk elderly people (SUPERBRAIN), we evaluated the impact of a 24-week facility-based multidomain intervention (FMI) and home-based MI (HMI) on cortical thickness, brain volume, and the serum brain-derived neurotrophic factor (BDNF). Totally, 152 participants, aged 60–79 years without dementia but with ≥ 1 modifiable dementia risk factor, were randomly assigned to the FMI, HMI, or control groups. Among them, 55 participants (20 FMI, 19 HMI, and 16 controls) underwent brain MRI at baseline and 24 weeks. We compared changes in global/regional mean cortical thickness at the region-of-interest (ROI) between the intervention and control groups. The changes in the total cortical gray matter volume and global mean cortical thickness were compared using analysis of covariance with age, sex, and education as covariates. ComBat site harmonization was applied for cortical thickness values across the scanners. ROI-based analysis was controlled for multiple comparisons, with a false discovery rate threshold of p < 0.05. Serum BDNF levels were significantly higher in the FMI group than in the control group (p = 0.029). Compared with the control group, the mean global cortical thickness increased in the FMI group (0.033 ± 0.070 vs. − 0.003 ± 0.040, p = 0.013); particularly, cortical thickness of the bilateral frontotemporal lobes, cingulate gyri, and insula increased. The increase in cortical thickness and serum BDNF in the FMI group suggests that group preventive strategies at the facility may be beneficial through structural neuroplastic changes in brain areas, which facilitates learning and neurotrophic factors.

The Effect of Anxiety on Regional Brain Volumes in the National Alzheimer’s Coordinating Center Uniform Data Set

Anxiety has been associated with greater risk of Alzheimer’s disease (AD) and existing research has identified structural differences in regional brain tissue in anxious compared to healthy samples, but results have been variable and somewhat inconsistent. We sought to determine the effect of anxiety on regional brain volumes by cognitive and apolipoprotein e (APOE) e4 status using data from a large, national dataset. A secondary analysis of the National Alzheimer’s Coordinating Center Uniform (NACC) Data Set was conducted using complete MRI data from 1,371 participants (mean age: 70.5; SD: 11.7). Multiple linear regression was used to estimate the adjusted effect of anxiety (via the Neuropsychiatric Inventory Questionnaire) on regional brain volumes through measurement of 30 structural MRI biomarkers. Anxiety was associated with lower total brain and total cortical gray matter volumes and increased lateral ventricular volume (p<.05). Lower mean volumes were also observed in all hippocampal, frontal lobe, parietal lobe, temporal lobe, and right occipital lobe volumes among participants who reported anxiety. Conversely, greater ventricular volumes were also correlated with anxiety. Findings suggest that anxiety is associated with significant atrophy in multiple brain regions and ventricular enlargement, even after controlling for intracranial volume and demographic covariates. Anxiety-related changes to brain morphology may contribute to greater AD risk.

Longitudinal alteration of cortical thickness and volume in high-impact sports

Collegiate football athletes are subject to repeated head impacts. The purpose of this study was to determine whether this exposure can lead to changes in brain structure. This prospective cohort study was conducted with up to 4 years of follow-up on 63 football (high-impact) and 34 volleyball (control) male collegiate athletes with a total of 315 MRI scans (after exclusions: football n ​= ​50, volleyball n ​= ​24, total scans ​= ​273) using high-resolution structural imaging. Volumetric and cortical thickness estimates were derived using FreeSurfer 5.3’s longitudinal pipeline. A linear mixed-effects model assessed the effect of group (football vs. volleyball), time from baseline MRI, and the interaction between group and time. We confirmed an expected developmental decrement in cortical thickness and volume in our cohort (p ​< ​.001). Superimposed on this, total cortical gray matter volume (p ​= ​.03) and cortical thickness within the left hemisphere (p ​= ​.04) showed a group by time interaction, indicating less age-related volume reduction and thinning in football compared to volleyball athletes. At the regional level, sport by time interactions on thickness and volume were identified in the left orbitofrontal (p ​= ​.001), superior temporal (p ​= ​.001), and postcentral regions (p ​< ​.001). Additional cortical thickness interactions were found in the left temporal pole (p ​= ​.003) and cuneus (p ​= ​.005). At the regional level, we also found main effects of sport in football athletes characterized by reduced volume in the right hippocampus (p ​= ​.003), right superior parietal cortical gray (p ​< ​.001) and white matter (p ​< ​.001), and increased volume of the left pallidum (p ​= ​.002). Within football, cortical thickness was higher with greater years of prior play (left hemisphere p ​= ​.013, right hemisphere p ​= ​.005), and any history of concussion was associated with less cortical thinning (left hemisphere p ​= ​.010, right hemisphere p ​= ​.011). Additionally, both position-associated concussion risk (p ​= ​.002) and SCAT scores (p ​= ​.023) were associated with less of the expected volume decrement of deep gray structures. This prospective longitudinal study comparing football and volleyball athletes shows divergent age-related trajectories of cortical thinning, possibly reflecting an impact-related alteration of normal cortical development. This warrants future research into the underlying mechanisms of impacts to the head on cortical maturation.

Brain morphometry of preschool age children affected by autism spectrum disorder: Correlation with clinical findings.

The aim of our study was to use a combined imaging and clinical approach to identify possible patterns of clinical and imaging findings in a cohort of preschool age autism spectrum disorder (ASD) patients. In order to identify imaging patterns that could be related to specific clinical features, a selected group of ASD patients (age range 3-6 years) without dysmorphic features, epilepsy or other major neurological signs, malformations or other lesions at MRI was subjected to brain volumetric analysis using semiautomatic brain segmentation. An age-matched group of typically developing children was subjected to the same analysis. Our results were consistent with previous literature: Total gray matter volume, total cortical gray matter volume and amygdalar volumes were significantly greater in the ASD group than the control group. When we divided the study group into subgroups on the basis of clinical findings such as high- or low-functioning, or verbal and nonverbal, the only significant difference between verbal and nonverbal subjects was in cerebellar hemispheric size. In conclusions, our results confirm that newer brain MRI techniques using semiautomatic brain segmentation can provide information useful for defining the differences between ASD patients and controls, particularly if they form part of an integrated approach between MRI and cognitive-behavioral and genetic data. Clin. Anat. 32:143-150, 2019. © 2018 Wiley Periodicals, Inc. HIGHLIGHTS: Combined imaging and clinical approach in autism spectrum disorders Semiautomatic brain segmentation in a selected preschool age ASD group Reduced total cerebellar white matter volume in non-verbal ASD patients.

Midlife anticholinergic drug use, risk of Alzheimer's disease, and brain atrophy in community-dwelling older adults

IntroductionWe examined how long-term anticholinergic (AC) drug use beginning at midlife affects risk of Alzheimer's disease (AD) and rates of brain atrophy in cognitively normal older adults. MethodsWe followed 723 individuals (mean baseline age 52.3 years; mean follow-up interval 20.1 years) in the Baltimore Longitudinal Study of Aging. The AC drug exposure was defined using the Anticholinergic Cognitive Burden Scale: Nonusers (n = 404), as well as participants exposed to medications with AC activity but without known clinically relevant negative cognitive effects (i.e., “possible AC users”; n = 185) and those exposed to AC drugs with established and clinically relevant negative cognitive effects (i.e., “definite AC users”; n = 134). The neuroimaging sample included 93 participants who remained cognitively normal through follow-up and underwent serial magnetic resonance imaging (n = 93, 724 brain scans, mean follow-up interval 8.2 years, and baseline age 68.6 years). ResultsPossible AC users, but not definite AC users, showed increased risk of incident AD compared with nonusers (hazard ratio, 1.63; 95% confidence interval, 1.02–2.61; P = .04) and greater rates of atrophy in total cortical gray matter volume compared with nonusers (β = −0.74, P = .018). Faster rates of brain atrophy were also observed among possible AC users in the right posterior cingulate, as well as right middle frontal and left superior temporal gyri. Data on frequency and duration of medication use were available in only approximately half of the sample. Among these participants, definite AC users had both shorter duration and lower frequency of medication use relative to possible AC users. DiscussionLong-term exposure to medications with mild AC activity during midlife is associated with increased risk of AD and accelerated brain atrophy.

Regional Neocortical Gray Matter Structure and Sleep Fragmentation in Older Adults.

To test the hypothesis that greater sleep fragmentation is associated with regionally decreased cortical gray matter volume in older community-dwelling adults without cognitive impairment. We studied 141 community-dwelling older adults (median age 82.9; 73% female) without cognitive impairment or stroke, and not using sedative/ hypnotic medications, participating in the Rush Memory and Aging Project. We quantified sleep fragmentation from 7 d of actigraphy using the metric kRA and related this to total cortical gray matter volume, and regional gray matter volume in 34 cortical regions quantified by automated segmentation of magnetic resonance imaging data. We determined statistical significance and accounted for multiple comparisons by empirically estimating the false discovery rate by permutation. Lower total cortical gray matter volume was associated with higher sleep fragmentation (coefficient +0.23, standard error [SE] 0.11, P = 0.037). Lower gray matter volumes in four cortical regions were accompanied by higher sleep fragmentation with a false discovery rate < 0.05: the left (coefficient +0.36, SE 0.10, P = 2.7 × 10(-4)) and right (coefficient +0.31, SE 0.10, P = 4.0 × 10(-3)) lateral orbitofrontal cortices, and the adjacent left (coefficient +0.31, SE 0.10, 5.4 × 10(-4)) and right (coefficient +0.39, SE 0.10, P = 1.2 × 10(-4)) inferior frontal gyri pars orbitalis. These associations were unchanged after accounting for age, sex, education, depression, cognitive function, and a number of medical comorbidities. Lower cortical gray matter volume in the lateral orbitofrontal cortex and inferior frontal gyrus pars orbitalis is associated with greater sleep fragmentation in older community-dwelling adults. Further work is needed to clarify whether this is a consequence of or contributor to sleep fragmentation. A commentary on this article appears in this issue on page 15.

Antipsychotics Linked to Cortical Loss in Patients With Schizophrenia

Back to table of contents Previous article Next article Clinical and Research NewsFull AccessAntipsychotics Linked to Cortical Loss in Patients With SchizophreniaVabren WattsVabren WattsSearch for more papers by this authorPublished Online:28 Sep 2015https://doi.org/10.1176/appi.pn.2015.10a14AbstractThough antipsychotic use in patients with schizophrenia was found to be associated with reduction in cortical gray matter volume, first-generation antipsychotics may cause greater reduction than second-generation antipsychotics.Although it is well established that patients with schizophrenia have deficits in cortical gray matter, a meta-analysis published in the September issue of Biological Psychiatry suggests that cumulative antipsychotic intake and the type of antipsychotic a patient with schizophrenia takes may influence the degree of gray matter loss over time.Triff/ShutterstockResearchers from the Department of Mental Health at the University of Brescia School of Medicine in Italy led a retrospective study to determine whether changes in cortical gray matter differ between patients with schizophrenia who take first-generation antipsychotics and those who take second-generation antipsychotics.“The role played by antipsychotic treatment on the pathophysiologic trajectory of brain abnormalities in schizophrenia is currently a matter of lively debate,” explained the study’s lead author, Antonio Vita, M.D., Ph.D., a professor of psychiatry at the University of Brescia, in an interview with Psychiatric News. As Vita and his colleagues noted in the paper, qualitative reviews and independent studies addressing the topic of structural brain changes in schizophrenia in relation to antipsychotic treatment have yielded inconclusive results, with few looking at whether a patient was prescribed first-generation or second-generation antipsychotics.To evaluate the influence of antipsychotic treatment on cortical gray matter volume in patients with schizophrenia, the researchers compiled data from 18 longitudinal magnetic resonance imaging studies, published from January 1, 1983, to March 31, 2014, totaling 1,155 patients with schizophrenia and 911 healthy controls. The results showed that patients with schizophrenia showed significantly greater loss of total cortical gray matter volume than healthy controls, which was related to cumulative antipsychotic intake during the interval between imaging scans among the longitudinal studies. When comparing changes in cortical gray matter volumes in patients who were treated with first-generation antipsychotics (FGAs) with those who were treated with second-generation antipsychotics (SGAs), the researchers found that greater gray matter loss was correlated with higher mean daily dose in studies including patients treated with FGAs, whereas less progressive loss was observed in studies including only patients treated with SGAs. “On the whole, our results indicate that the putative contributory role of antipsychotic treatment in reducing the volume of cortical [gray matter] in schizophrenia cannot be generalized and appears to be less evident for SGAs, which seem to be associated with less loss of brain tissue,” the study authors wrote.Vita told Psychiatric News that many issues remain to be clarified. “We still do not know whether the effects on the brain of antipsychotics vary as a function of age and stage of illness, or whether they may occur only when a certain threshold of exposure [daily dose or cumulative dose] is reached,” said Vita. He concluded that “clarification of these issues will have crucial importance in the clinical management of schizophrenia and will allow a better understanding of the mechanisms underlying the progression of structural brain abnormalities in schizophrenia.”The study was funded by a grant from the Lombardia Region. ■“The Effect of Antipsychotic Treatment on Cortical Gray Matter Changes in Schizophrenia: Does the Class Matter? A Meta-analysis and Meta-regression of Longitudinal Magnetic Resonance Imaging Studies” can be accessed here. ISSUES NewArchived

Cortical structural abnormalities in very preterm children at 7 years of age

We analyzed long-lasting alterations in brain morphometry associated with preterm birth using volumetric and surface-based analyses applied to children at age 7years. Comparison of 24 children born very preterm (VPT) to 24 healthy term-born children revealed reductions in total cortical gray matter volume, white matter volume, cortical surface area and gyrification index. Regional cortical shape abnormalities in VPT children included the following: shallower anterior superior temporal sulci, smaller relative surface area in the inferior sensori-motor cortex and posterior superior temporal cortex, larger relative surface area and a cingulate sulcus that was shorter or more interrupted in medial frontoparietal cortex. These findings indicate a complex pattern of regional vulnerabilities in brain development that may contribute to the diverse and long-lasting neurobehavioral consequences that can occur after very premature birth.

Reading skill and structural brain development

Reading is a learned skill that is likely influenced by both brain maturation and experience. Functional imaging studies have identified brain regions important for skilled reading, but the structural brain changes that co-occur with reading acquisition remain largely unknown. We investigated maturational volume changes in brain reading regions and their association with performance on reading measures. Sixteen typically developing children (5-15 years old, eight boys, mean age of sample=10.06 ± 3.29) received two MRI scans (mean interscan interval=2.19 years), and were administered a battery of cognitive measures. Volume changes between time points in five bilateral cortical regions of interest were measured, and assessed for relationships to three measures of reading. Better baseline performances on measures of word reading, fluency, and rapid naming, independent of age and total cortical gray matter volume change, were associated with volume decrease in the left inferior parietal cortex. Better baseline performance on a rapid naming measure was associated with volume decrease in the left inferior frontal region. These results suggest that children who are better readers, and who perhaps read more than less skilled readers, exhibit different development trajectories in brain reading regions. Understanding relationships between reading performance, reading experience, and brain maturation trajectories may help with the development and evaluation of targeted interventions.

Poorer physical fitness is associated with reduced structural brain integrity in heart failure

ObjectivePhysical fitness is an important correlate of structural and functional integrity of the brain in healthy adults. In heart failure (HF) patients, poor physical fitness may contribute to cognitive dysfunction and we examined the unique contribution of physical fitness to brain structural integrity among patients with HF. MethodsSixty-nine HF patients performed the Modified Mini Mental State examination (3MS) and underwent brain magnetic resonance imaging. All participants completed the 2-minute step test (2MST), a brief measure of physical fitness. We examined the associations between cognitive performance, physical fitness, and three indices of global brain integrity: total cortical gray matter volume, total white matter volume, and whole brain cortical thickness. ResultsRegression analyses adjusting for demographic characteristics, medical variables (e.g., left ventricular ejection fraction), and intracranial volume revealed reduced performance on the 2MST were associated with decreased gray matter volume and thinner cortex (p<.05). Follow up analyses showed that reduced gray matter volume and decreased cortical thickness were associated with poorer 3MS scores (p<.05). ConclusionsPoor physical fitness is common in HF and associated with reduced structural brain integrity. Prospective studies are needed to elucidate underlying mechanisms for the influence of physical fitness on brain health in HF.

EEG upper/low alpha frequency power ratio relates to temporo-parietal brain atrophy and memory performances in mild cognitive impairment.

Objective: Temporo-parietal cortex thinning is associated to mild cognitive impairment (MCI) due to Alzheimer disease (AD). The increase of EEG upper/low alpha power ratio has been associated with AD-converter MCI subjects. We investigated the association of alpha3/alpha2 ratio with patterns of cortical thickness in MCI.Materials and Methods: Seventy-four adult subjects with MCI underwent clinical and neuropsychological evaluation, electroencephalogram (EEG) recording and high resolution 3D magnetic resonance imaging. Alpha3/alpha2 power ratio as well as cortical thickness was computed for each subject. Three MCI groups were detected according to increasing tertile values of upper/low alpha power ratio. Difference of cortical thickness among the groups was estimated. Pearson’s r was used to assess the topography of the correlation between cortical thinning and memory impairment.Results: High upper/low alpha power ratio group had total cortical gray matter volume reduction of 471 mm2 than low upper/low alpha power ratio group (p < 0.001). Upper/low alpha group showed a similar but less marked pattern (160 mm2) of cortical thinning when compared to middle upper/low alpha power ratio group (p < 0.001). Moreover, high upper/low alpha group had wider cortical thinning than other groups, mapped to the Supramarginal and Precuneus bilaterally. Finally, in high upper/low alpha group temporo-parietal cortical thickness was correlated to memory performance. No significant cortical thickness differences was found between middle and low alpha3/alpha2 power ratio groups.Conclusion: High EEG upper/low alpha power ratio was associated with temporo-parietal cortical thinning and memory impairment in MCI subjects. The combination of EEG upper/low alpha ratio and cortical thickness measure could be useful for identifying individuals at risk for progression to AD dementia and may be of value in clinical context.

Gray matter volume deficits are associated with motor and attentional impairments in adolescents with schizophrenia

Cognitive deficits have been well described in adolescents with schizophrenia, but little is known about the neuroanatomical basis of these abnormalities. The authors examined whether neuropsychological deficits observed in adolescents with schizophrenia were associated with cortical gray matter volume deficits. Volumes of the superior frontal gyrus, anterior cingulate gyrus and orbital frontal lobe were outlined manually from contiguous MR images and automatically segmented into gray and white matter in 52 patients and 48 healthy volunteers. Subjects received a comprehensive neuropsychological test battery, assessing five different functional domains: executive, attention, verbal memory, motor and sensory motor. Children and adolescents with schizophrenia were found to have lower total cortical and lower superior frontal gyrus gray matter volumes and lower test scores across all functional domains compared to healthy volunteers. Among patients, the lower total cortical gray matter volume was associated with worse functioning on the attention and motor domains. Our findings point to widespread, perhaps multifocal, pathology as contributing to cognitive dysfunction in adolescents with schizophrenia.

Cognitive and motor impairments are related to gray matter volume deficits in schizophrenia

This study examined whether the neuropsychological deficits observed in patients with schizophrenia were related to cortical gray matter volume deficits in these patients. All subjects were men and included 34 patients with DSM-III-R Schizophrenia and 47 age-matched healthy controls. Subjects received a battery of 21 tests, assessing four different functional domains: executive functions, short-term memory and production, declarative memory, and motor ability. MRI volumes were corrected for normal variation in head size and age, and neuropsychological test scores were corrected for normal variation in age. The schizophrenic group had significantly smaller cortical gray matter volumes (p < .05) and lower test scores in all functional domain than the control group (p = .0001). Within the schizophrenic group, lower scores in each domain were significantly correlated with smaller total cortical gray matter volumes; however, no predictable relationships were observed between neuropsychological test performance and the volumes of specific cortical regions.