Developmental Differences Between the Limbic and Neocortical Telencephalic Wall: An Intrasubject Slice-Matched 3 T MRI-Histological Correlative Study in Humans.

The purpose of the study was to investigate the interrelation of the signal intensities and thicknesses of the transient developmental zones in the cingulate and neocortical telencephalic wall, using T2-weighted 3 T-magnetic resonance imaging (MRI) and histological scans from the same brain hemisphere. The study encompassed 24 postmortem fetal brains (15-35 postconceptional weeks, PCW). The measurements were performed using Fiji and NDP.view2. We found that T2w MR signal-intensity curves show a specific regional and developmental stage profile already at 15 PCW. The MRI-histological correlation reveals that the subventricular-intermediate zone (SVZ-IZ) contributes the most to the regional differences in the MRI-profile and zone thicknesses, growing by a factor of 2.01 in the cingulate, and 1.78 in the neocortical wall. The interrelations of zone or wall thicknesses, obtained by both methods, disclose a different rate and extent of shrinkage per region (highest in neocortical subplate and SVZ-IZ) and stage (highest in the early second half of fetal development), distorting the zones' proportion in histological sections. This intrasubject, slice-matched, 3 T correlative MRI-histological study provides important information about regional development of the cortical wall, critical for the design of MRI criteria for prenatal brain monitoring and early detection of cortical or other brain pathologies in human fetuses.

The Relationship Between the Uncinate Fasciculus and Anxious Temperament Is Evolutionarily Conserved and Sexually Dimorphic.

BACKGROUND: Anxious temperament (AT) is an early-life heritable trait that predisposes individuals to develop anxiety and depressive disorders. Our previous work in preadolescent children suggests alterations in the uncinate fasciculus (UF), the white matter tract that connects prefrontal with limbic regions, in boys with anxiety disorders. Here, using a nonhuman primate model of AT, we tested whether this sexually dimorphic finding is evolutionarily conserved and examined the extent to which heritable and environmental influences contribute to UF microstructure. METHODS: Diffusion tensor images were collected in 581 young rhesus monkeys (1.89 ± 0.77 years old; 43.9% female). Using tract-based analyses, we assessed the relationship among AT, UF microstructure (as measured with fractional anisotropy), and sex. Heritability of tract microstructure was determined using oligogenic linkage analysis of this large multigenerational pedigree. RESULTS: We predicted and found a negative relation between AT and UF fractional anisotropy in male but not female monkeys (AT × sex; p = .032, 1-tailed). Additionally, heritability analyses revealed that variation in UF fractional anisotropy was largely due to nonheritable factors (h2 = 0.185, p = .077). CONCLUSIONS: These results demonstrate a cross-species, male-specific relation between UF microstructure and anxiety and provide a potential substrate for anxiety-related prefrontal-limbic dysregulation. The heritability analyses point to the importance of environmental influences on UF microstructure, which could be important in mediating the nonheritable components of pathological anxiety. These findings have the potential to guide new treatment strategies for childhood anxiety disorders and further support the use of nonhuman primates as a translational model to discover mechanisms underlying the development of anxiety.

White matter architecture in major depression with anxious distress symptoms.

BACKGROUND: Comorbid anxious distress is common in Major Depressive Disorder (MDD), and associated with significantly worse clinical course and treatment response. While DSM-5 recently introduced the Anxious Distress (AD) specifier as a potentially useful symptom-based subtyping scheme for MDD, its neurobiological underpinnings remain unclear. The current study hence uniquely probed whether MDD with co-occurring AD (MDD/AD+) relates to distinct perturbations in frontolimbic white matter (WM) pathways tentatively theorized in MDD/AD+ pathophysiology. METHODS: Tract-based spatial statistics (TBSS) was therefore used to analyze diffusion tensor imaging data on WM microstructure, in MDD/AD+ patients (N = 20) relative to MDD patients without AD (MDD/AD-; N = 29) and healthy controls (HC; N = 39). Using TBSS, we probed fractional anisotropy and axial/radial/mean diffusivity as proxies for WM integrity. Categorical (between-groups) and dimensional (within-patients) analyses subsequently assessed how Anxious Distress in MDD impacts frontolimbic WM connectivity. Receiver-Operating Characteristics additionally assessed classification capabilities of between-groups WM effects. RESULTS: Compared to MDD/AD- and HC participants, MDD/AD+ patients exhibited diminished integrity within the anterior thalamic radiation (ATR). Higher AD specifier scores within MDD patients additionally related to diminished integrity of the uncinate fasciculus and cingulum pathways. These effects were not confounded by key clinical (e.g., comorbid anxiety disorder) and sociodemographic (e.g., age/sex) factors, with altered ATR integrity moreover successfully classifying MDD/AD+ patients from MDD/AD- and HC participants (90% sensitivity | 73% specificity | 77% accuracy). CONCLUSIONS: These findings collectively link MDD/AD+ to distinct WM anomalies in frontolimbic tracts important to adaptive emotional functioning, and may as such provide relevant, yet preliminary, clues on MDD/AD+ pathophysiology.

Cerebellar, limbic, and midbrain volume alterations in sudden unexpected death in epilepsy.

OBJECTIVE: The processes underlying sudden unexpected death in epilepsy (SUDEP) remain elusive, but centrally mediated cardiovascular or respiratory collapse is suspected. Volume changes in brain areas mediating recovery from extreme cardiorespiratory challenges may indicate failure mechanisms and allow prospective identification of SUDEP risk. METHODS: We retrospectively imaged SUDEP cases (n = 25), patients comparable for age, sex, epilepsy syndrome, localization, and disease duration who were high-risk (n = 25) or low-risk (n = 23), and age- and sex-matched healthy controls (n = 25) with identical high-resolution T1-weighted scans. Regional gray matter volume, determined by voxel-based morphometry, and segmentation-derived structure sizes were compared across groups, controlling for total intracranial volume, age, and sex. RESULTS: Substantial bilateral gray matter loss appeared in SUDEP cases in the medial and lateral cerebellum. This was less prominent in high-risk subjects and absent in low-risk subjects. The periaqueductal gray, left posterior and medial thalamus, left hippocampus, and bilateral posterior cingulate also showed volume loss in SUDEP. High-risk subjects showed left thalamic volume reductions to a lesser extent. Bilateral amygdala, entorhinal, and parahippocampal volumes increased in SUDEP and high-risk patients, with the subcallosal cortex enlarged in SUDEP only. Disease duration correlated negatively with parahippocampal volume. Volumes of the bilateral anterior insula and midbrain in SUDEP cases were larger the closer to SUDEP from magnetic resonance imaging. SIGNIFICANCE: SUDEP victims show significant tissue loss in areas essential for cardiorespiratory recovery and enhanced volumes in areas that trigger hypotension or impede respiratory patterning. Those changes may shed light on SUDEP pathogenesis and prospectively detect patterns identifying those at risk.

Limbic and Basal Ganglia Neuroanatomical Correlates of Gait and Executive Function: Older Adults With Mild Cognitive Impairment and Intact Cognition.

OBJECTIVE: This study aimed to examine differences in spatiotemporal gait parameters between older adults with amnestic mild cognitive impairment and normal cognition and to examine limbic and basal ganglia neural correlates of gait and executive function in older adults without dementia. DESIGN: This was a cross-sectional study of 46 community-dwelling older adults, ages 70-95 yrs, with amnestic mild cognitive impairment (n = 23) and normal cognition (n = 23). Structural magnetic resonance imaging was used to attain volumetric measures of limbic and basal ganglia structures. Quantitative motion analysis was used to measure spatiotemporal parameters of gait. The Trail Making Test was used to assess executive function. RESULTS: During fast-paced walking, older adults with amnestic mild cognitive impairment demonstrated significantly slower gait speed and shorter stride length compared with older adults with normal cognition. Stride length was positively correlated with hippocampal, anterior cingulate, and nucleus accumbens volumes (P < 0.05). Executive function was positively correlated with hippocampal, anterior cingulate, and posterior cingulate volumes (P < 0.05). CONCLUSIONS: Compared with older adults with normal cognition, those with amnestic mild cognitive impairment demonstrated slower gait speed and shorter stride length, during fast-paced walking, and lower executive function. Hippocampal and anterior cingulate volumes demonstrated moderate positive correlation with both gait and executive function, after adjusting for age. TO CLAIM CME CREDITS: Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME CME OBJECTIVES: Upon completion of this article, the reader should be able to: (1) discuss gait performance and cognitive function in older adults with amnestic mild cognitive impairment versus normal cognition, (2) discuss neurocorrelates of gait and executive function in older adults without dementia, and (3) recognize the importance of assessing gait speed and cognitive function in the clinical management of older adults at risk for dementia. LEVEL: Advanced ACCREDITATION: The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.The Association of Academic Physiatrists designates this Journal-based CME activity for a maximum of 0.5 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

Preferential susceptibility of limbic cortices to microstructural damage in temporal lobe epilepsy: A quantitative T1 mapping study.

The majority of MRI studies in temporal lobe epilepsy (TLE) have utilized morphometry to map widespread cortical alterations. Morphological markers, such as cortical thickness or grey matter density, reflect combinations of biological events largely driven by overall cortical geometry rather than intracortical tissue properties. Because of its sensitivity to intracortical myelin, quantitative measurement of longitudinal relaxation time (qT1) provides and an in vivo proxy for cortical microstructure. Here, we mapped the regional distribution of qT1 in a consecutive cohort of 24 TLE patients and 20 healthy controls. Compared to controls, patients presented with a strictly ipsilateral distribution of qT1 increases in temporopolar, parahippocampal and orbitofrontal cortices. Supervised statistical learning applied to qT1 maps could lateralize the seizure focus in 92% of patients. Intracortical profiling of qT1 along streamlines perpendicular to the cortical mantle revealed marked effects in upper levels that tapered off at the white matter interface. Findings remained robust after correction for cortical thickness and interface blurring, suggesting independence from previously reported morphological anomalies in this disorder. Mapping of qT1 along hippocampal subfield surfaces revealed marked increases in anterior portions of the ipsilateral CA1-3 and DG that were also robust against correction for atrophy. Notably, in operated patients, qualitative histopathological analysis of myelin stains in resected hippocampal specimens confirmed disrupted internal architecture and fiber organization. Both hippocampal and neocortical qT1 anomalies were more severe in patients with early disease onset. Finally, analysis of resting-state connectivity from regions of qT1 increases revealed altered intrinsic functional network embedding in patients, particularly to prefrontal networks. Analysis of qT1 suggests a preferential susceptibility of ipsilateral limbic cortices to microstructural damage, possibly related to disrupted myeloarchitecture. These alterations may reflect atypical neurodevelopment and affect the integrity of fronto-limbic functional networks.

Subtypes of breast cancer show different spatial distributions of brain metastases.

The aim of our study was to test the hypothesis that the spatial distribution of breast cancer brain metastases (BM) differ according to their biological subtypes. MR images of 100 patients with BM from primary breast cancer were retrospectively reviewed. Patients were divided according to the biological subtype of the primary tumor, (triple-negative: 24, HER2 positive: 48, luminal: 28). All images marked with BMs were standardized to the human brain MRI atlas provided by the Montreal Neurological Institute 152 database. Distribution pattern of BM was evaluated with intra-group and intergroup analysis. In intra-group analysis, hot spots of metastases from triple-negative are evenly distributed in the brain, meanwhile BMs from HER2 positive and luminal type occur dominantly in occipital lobe and cerebellum. In intergroup analysis, BMs from triple-negative type occurred more often in frontal lobe, limbic region, and parietal lobe, compared with other types (P < .05). Breast cancer subtypes tend to demonstrate different spatial distributions of their BMs. These findings may have direct implications for dose modulation in prophylactic irradiation as well as for differential diagnoses. Thus, this result should be validated in future study with a larger population.

Behavioral sensitization to methamphetamine induces specific interneuronal mRNA pathology across the prelimbic and orbitofrontal cortices.

Schizophrenia is associated with significant pathophysiological changes to interneurons within the prefrontal cortex (PFC), with mRNA and protein changes associated with the GABA network localized to specific interneuron subtypes. Methamphetamine is a commonly abused psychostimulant that can induce chronic psychosis and symptoms that are similar to schizophrenia, suggesting that chronic METH induced psychosis may be associated with similar brain pathology to schizophrenia in the PFC. The aim of this study, therefore, was to examine mRNA expression of interneuron markers across two regions of the PFC (prelimbic (PRL) and orbitofrontal cortices (OFC)) following METH sensitization, an animal model of METH psychosis. We also studied the association between GABA mRNA expression and interneuronal mRNA expression to identify whether particular changes to the GABA network could be localized to a specific inhibitory cellular phenotype. METH sensitization increased the transcriptional expression of calbindin, calretinin, somatostatin, cholecyctokinin and vasoactive intestinal peptide in the PRL while parvalbumin, calbindin, cholectokinin and vasoactive intestinal peptide were upregulated in the OFC. Based on our previous findings, we also found significant correlations between GAD67, GAT1 and parvalbumin while GAD67, GAD65 and GAT1 were positively correlated with cholecystokinin in the PRL of METH sensitized rats. Within the OFC, the expression of GABAAα1 was positively correlated with somatostatin while GABAAα5 was negatively associated with somatostatin and calbindin. These findings suggest that METH sensitization differentially changes the expression of mRNAs encoding for multiple peptides and calcium binding proteins across the PRL and the OFC. Furthermore, these findings support that changes to the GABA network may also occur within specific cell types. These results, therefore, provide the first evidence that METH sensitization mediates differential interneuronal pathology across the PRL and OFC and such changes could have profound consequences on behavior and cognitive output.

Influence of BclI C/G (rs41423247) on hippocampal shape and white matter integrity of the parahippocampal cingulum in major depressive disorder.

We investigated the interactive effects of BclI C/G (rs41423247) allelic variants and the diagnosis of major depressive disorder (MDD) on hippocampal shape and integrity of the left parahippocampal subdivision of the cingulum. Fifty-two patients with MDD and 52 healthy controls (HCs) underwent T1-weighted structural magnetic resonance imaging and BclI C/G (rs41423247) genotyping. We analyzed hippocampal shape using the FIRST module of FSL and analyzed white matter (WM) integrity using diffusion tensor imaging (DTI) and tract-based spatial statistics (TBSS). Significant alterations in left hippocampal shape and decreased fractional anisotropy (FA) values of the left parahippocampal cingulum were observed in MDD patients, compared to HCs. In addition, MDD patients of the BclI minor (G-) allele carrier group showed significant alterations in left hippocampal shape and decreased FA values of the left parahippocampal cingulum compared to BclI minor (G-) allele carrier HCs. No significant differences between diagnostic subgroups of the C/C homozygotes were observed. Our study provides evidence for alterations in hippocampal shape and decreased integrity of the WM region associated with the hippocampus in MDD, and for the possible influence of BclI C/G polymorphism (rs41423247) on hippocampal shape and integrity of the parahippocampal subdivision of the cingulum in depression.

Dysfunctional epileptic neuronal circuits and dysmorphic dendritic spines are mitigated by platelet-activating factor receptor antagonism.

Temporal lobe epilepsy or limbic epilepsy lacks effective therapies due to a void in understanding the cellular and molecular mechanisms that set in motion aberrant neuronal network formations during the course of limbic epileptogenesis (LE). Here we show in in vivo rodent models of LE that the phospholipid mediator platelet-activating factor (PAF) increases in LE and that PAF receptor (PAF-r) ablation mitigates its progression. Synthetic PAF-r antagonists, when administered intraperitoneally in LE, re-establish hippocampal dendritic spine density and prevent formation of dysmorphic dendritic spines. Concomitantly, hippocampal interictal spikes, aberrant oscillations, and neuronal hyper-excitability, evaluated 15-16 weeks after LE using multi-array silicon probe electrodes implanted in the dorsal hippocampus, are reduced in PAF-r antagonist-treated mice. We suggest that over-activation of PAF-r signaling induces aberrant neuronal plasticity in LE and leads to chronic dysfunctional neuronal circuitry that mediates epilepsy.

The White Matter Microintegrity Alterations of Neocortical and Limbic Association Fibers in Major Depressive Disorder and Panic Disorder: The Comparison.

The studies regarding to the comparisons between major depressive disorder (MDD) and panic disorder (PD) in the microintegrity of white matter (WM) are uncommon. Therefore, we tried to a way to classify the MDD and PD. Fifty-three patients with 1st-episode medication-naive PD, 54 healthy controls, and 53 patients with 1st-episode medication-naive MDD were enrolled in this study. The controls and patients were matched for age, gender, education, and handedness. The diffusion tensor imaging scanning was also performed. The WM microintegrity was analyzed and compared between 3 groups of participants (ANOVA analysis) with age and gender as covariates. The MDD group had lower WM microintegrity than the PD group in the left anterior thalamic radiation, left uncinate fasciculus, left inferior fronto-occipital fasciculus, and bilateral corpus callosum. The MDD group had reductions in the microintegrity when compared to controls in the bilateral superior longitudinal fasciculi, inferior longitudinal fasciculi, inferior fronto-occipital fasciculi, and corpus callosum. The PD group had lower microintegrity in bilateral superior longitudinal fasciculi and left inferior fronto-occipital fasciculus when compared to controls. The widespread pattern of microintegrity alterations in fronto-limbic WM circuit for MDD was different from restrictive pattern of alterations for PD.

Structural and Functional Alterations in Right Dorsomedial Prefrontal and Left Insular Cortex Co-Localize in Adolescents with Aggressive Behaviour: An ALE Meta-Analysis.

Recent neuroimaging work has suggested that aggressive behaviour (AB) is associated with structural and functional brain abnormalities in processes subserving emotion processing and regulation. However, most neuroimaging studies on AB to date only contain relatively small sample sizes. To objectively investigate the consistency of previous structural and functional research in adolescent AB, we performed a systematic literature review and two coordinate-based activation likelihood estimation meta-analyses on eight VBM and nine functional neuroimaging studies in a total of 783 participants (408 [224AB/184 controls] and 375 [215 AB/160 controls] for structural and functional analysis respectively). We found 19 structural and eight functional foci of significant alterations in adolescents with AB, mainly located within the emotion processing and regulation network (including orbitofrontal, dorsomedial prefrontal and limbic cortex). A subsequent conjunction analysis revealed that functional and structural alterations co-localize in right dorsomedial prefrontal cortex and left insula. Our results are in line with meta-analytic work as well as structural, functional and connectivity findings to date, all of which make a strong point for the involvement of a network of brain areas responsible for emotion processing and regulation, which is disrupted in AB. Increased knowledge about the behavioural and neuronal underpinnings of AB is crucial for the development of novel and implementation of existing treatment strategies. Longitudinal research studies will have to show whether the observed alterations are a result or primary cause of the phenotypic characteristics in AB.

A Neural Basis for Developmental Topographic Disorientation.

Developmental topographic disorientation (DTD) is a life-long condition in which affected individuals are severely impaired in navigating around their environment. Individuals with DTD have no apparent structural brain damage on conventional imaging and the neural mechanisms underlying DTD are currently unknown. Using functional and diffusion tensor imaging, we present a comprehensive neuroimaging study of an individual, J.N., with well defined DTD. J.N. has intact scene-selective responses in the parahippocampal place area (PPA), transverse occipital sulcus, and retrosplenial cortex (RSC), key regions associated with scene perception and navigation. However, detailed fMRI studies probing selective tuning properties of these regions, as well as functional connectivity, suggest that J.N.'s RSC has an atypical response profile and an atypical functional coupling to PPA compared with human controls. This deviant functional profile of RSC is not due to compromised structural connectivity. This comprehensive examination suggests that the RSC may play a key role in navigation-related processing and that an alteration of the RSC's functional properties may serve as the neural basis for DTD. SIGNIFICANCE STATEMENT: Individuals with developmental topographic disorientation (DTD) have a life-long impairment in spatial navigation in the absence of brain damage, neurological conditions, or basic perceptual or memory deficits. Although progress has been made in identifying brain regions that subserve normal navigation, the neural basis of DTD is unknown. Using functional and structural neuroimaging and detailed statistical analyses, we investigated the brain regions typically involved in navigation and scene processing in a representative DTD individual, J.N. Although scene-selective regions were identified, closer scrutiny indicated that these areas, specifically the retrosplenial cortex (RSC), were functionally disrupted in J.N. This comprehensive examination of a representative DTD individual provides insight into the neural basis of DTD and the role of the RSC in navigation-related processing.

Motor and Nonmotor Circuitry Activation Induced by Subthalamic Nucleus Deep Brain Stimulation in Patients With Parkinson Disease: Intraoperative Functional Magnetic Resonance Imaging for Deep Brain Stimulation.

OBJECTIVE: To test the hypothesis suggested by previous studies that subthalamic nucleus (STN) deep brain stimulation (DBS) in patients with Parkinson disease would affect the activity of motor and nonmotor networks, we applied intraoperative functional magnetic resonance imaging (fMRI) to patients receiving DBS. PATIENTS AND METHODS: Ten patients receiving STN DBS for Parkinson disease underwent intraoperative 1.5-T fMRI during high-frequency stimulation delivered via an external pulse generator. The study was conducted between January 1, 2013, and September 30, 2014. RESULTS: We observed blood oxygen level-dependent (BOLD) signal changes (false discovery rate <0.001) in the motor circuitry (including the primary motor, premotor, and supplementary motor cortices; thalamus; pedunculopontine nucleus; and cerebellum) and in the limbic circuitry (including the cingulate and insular cortices). Activation of the motor network was observed also after applying a Bonferroni correction (P<.001) to the data set, suggesting that across patients, BOLD changes in the motor circuitry are more consistent compared with those occurring in the nonmotor network. CONCLUSION: These findings support the modulatory role of STN DBS on the activity of motor and nonmotor networks and suggest complex mechanisms as the basis of the efficacy of this treatment modality. Furthermore, these results suggest that across patients, BOLD changes in the motor circuitry are more consistent than those in the nonmotor network. With further studies combining the use of real-time intraoperative fMRI with clinical outcomes in patients treated with DBS, functional imaging techniques have the potential not only to elucidate the mechanisms of DBS functioning but also to guide and assist in the surgical treatment of patients affected by movement and neuropsychiatric disorders. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01809613.

Methamphetamine-induced toxicity in indusium griseum of mice is associated with astro- and microgliosis.

The indusium griseum (IG), a thin layer of gray matter in contact with the dorsal surface of the corpus callosum and the lateral gray matter of the cingulate gyrus, has a common origin with hippocampus and shows similar organization with the dentate gyrus. Although some studies have examined the effect of methamphetamine (METH), an addictive and an illegal psychostimulant on this structure, quantitative effects and possible mechanism of actions of METH in this area are lacking. By applying two different protocols of equivalent METH administration (i.e., a high dose of 1 × 30 mg/kg and a lower and repeated injection dose of 3 × 10 mg/kg) and using a specific silver staining method in mice, we demonstrate that this drug produces degeneration in IG with both protocols, without affecting the dopaminergic system. Moreover, we observed quantitative increases in labeling of GFAP and Iba-1, markers of astro- and microgliosis, respectively, which suggest astrogliosis and microgliosis. Thus, our study provides morphological and semi-quantitative evidence that METH induces neurodegeneration in IG and that this damage is associated with astrogliosis and microgliosis in this area.

Structural covariance of superficial white matter in mild Alzheimer's disease compared to normal aging.

INTRODUCTION: Interindividual variations in regional structural properties covary across the brain, thus forming networks that change as a result of aging and accompanying neurological conditions. The alterations of superficial white matter (SWM) in Alzheimer's disease (AD) are of special interest, since they follow the AD-specific pattern characterized by the strongest neurodegeneration of the medial temporal lobe and association cortices. METHODS: Here, we present an SWM network analysis in comparison with SWM topography based on the myelin content quantified with magnetization transfer ratio (MTR) for 39 areas in each hemisphere in 15 AD patients and 15 controls. The networks are represented by graphs, in which nodes correspond to the areas, and edges denote statistical associations between them. RESULTS: In both groups, the networks were characterized by asymmetrically distributed edges (predominantly in the left hemisphere). The AD-related differences were also leftward. The edges lost due to AD tended to connect nodes in the temporal lobe to other lobes or nodes within or between the latter lobes. The newly gained edges were mostly confined to the temporal and paralimbic regions, which manifest demyelination of SWM already in mild AD. CONCLUSION: This pattern suggests that the AD pathological process coordinates SWM demyelination in the temporal and paralimbic regions, but not elsewhere. A comparison of the MTR maps with MTR-based networks shows that although, in general, the changes in network architecture in AD recapitulate the topography of (de)myelination, some aspects of structural covariance (including the interhemispheric asymmetry of networks) have no immediate reflection in the myelination pattern.

Associations between brain morphology and outcome in schizophrenia in a general population sample.

OBJECTIVE: To analyse associations between brain morphology and longitudinal and cross-sectional measures of outcomes in schizophrenia in a general population sample. METHODS: The sample was the Northern Finland 1966 Birth Cohort. In 1999-2001, structural brain MRI and measures of clinical and functional outcomes were analysed for 54 individuals with schizophrenia around the age of 34. Sex, total grey matter, duration of illness and the use of antipsychotic medication were used as covariates. RESULTS: After controlling for multiple covariates, increased density of the left limbic area was associated with less hospitalisations and increased total white matter volume with being in remission. Higher density of left frontal grey matter was associated with not being on a disability pension and higher density of the left frontal lobe and left limbic area were related to better functioning. Higher density of the left limbic area was associated with better longitudinal course of illness. CONCLUSIONS: This study, based on unselected general population data, long follow-up and an extensive database, confirms findings of previous studies, that morphological abnormalities in several brain structures are associated with outcome. The difference in brain morphology in patients with good and poor outcomes may reflect separable aetiologies and developmental trajectories in schizophrenia.