Predictive models demonstrate age‐dependent association of subcortical volumes and cognitive measures

Whether brain matter volume is correlated with cognitive functioning and higher intelligence is controversial. We explored this relationship by analysis of data collected on 193 healthy young and older adults through the “Leipzig Study for Mind–Body–Emotion Interactions” (LEMON) study. Our analysis involved four cognitive measures: fluid intelligence, crystallized intelligence, cognitive flexibility, and working memory. Brain subregion volumes were determined by magnetic resonance imaging. We normalized each subregion volume to the estimated total intracranial volume and conducted training simulations to compare the predictive power of normalized volumes of large regions of the brain (i.e., gray matter, cortical white matter, and cerebrospinal fluid), normalized subcortical volumes, and combined normalized volumes of large brain regions and normalized subcortical volumes. Statistical tests showed significant differences in the performance accuracy and feature importance of the subregion volumes in predicting cognitive skills for young and older adults. Random forest feature selection analysis showed that cortical white matter was the key feature in predicting fluid intelligence in both young and older adults. In young adults, crystallized intelligence was best predicted by caudate nucleus, thalamus, pallidum, and nucleus accumbens volumes, whereas putamen, amygdala, nucleus accumbens, and hippocampus volumes were selected for older adults. Cognitive flexibility was best predicted by the caudate, nucleus accumbens, and hippocampus in young adults and caudate and amygdala in older adults. Finally, working memory was best predicted by the putamen, pallidum, and nucleus accumbens in the younger group, whereas amygdala and hippocampus volumes were predictive in the older group. Thus, machine learning predictive models demonstrated an age‐dependent association between subcortical volumes and cognitive measures. These approaches may be useful in predicting the likelihood of age‐related cognitive decline and in testing of approaches for targeted improvement of cognitive functioning in older adults.     

Genetic and environmental influences on mean diffusivity and volume in subcortical brain regions

Increased mean diffusivity (MD) is hypothesized to reflect tissue degeneration and may provide subtle indicators of neuropathology as well as age‐related brain changes in the absence of volumetric differences. Our aim was to determine the degree to which genetic and environmental variation in subcortical MD is distinct from variation in subcortical volume. Data were derived from a sample of 387 male twins (83 MZ twin pairs, 55 DZ twin pairs, and 111 incomplete twin pairs) who were MRI scanned as part of the Vietnam Era Twin Study of Aging. Quantitative estimates of MD and volume for 7 subcortical regions were obtained: thalamus, caudate nucleus, putamen, pallidum, hippocampus, amygdala, and nucleus accumbens. After adjusting for covariates, bivariate twin models were fitted to estimate the size and significance of phenotypic, genotypic, and environmental correlations between MD and volume at each subcortical region. With the exception of the amygdala, familial aggregation in MD was entirely explained by additive genetic factors across all subcortical regions with estimates ranging from 46 to 84%. Based on bivariate twin modeling, variation in subcortical MD appears to be both genetically and environmentally unrelated to individual differences in subcortical volume. Therefore, subcortical MD may be an alternative biomarker of brain morphology for complex traits worthy of future investigation. Hum Brain Mapp 38:2589–2598, 2017. © 2017 Wiley Periodicals, Inc.     

Genetic influences on individual differences in longitudinal changes in global and subcortical brain volumes: Results of the ENIGMA plasticity working group

Structural brain changes that occur during development and ageing are related to mental health and general cognitive functioning. Individuals differ in the extent to which their brain volumes change over time, but whether these differences can be attributed to differences in their genotypes has not been widely studied. Here we estimate heritability (h²) of changes in global and subcortical brain volumes in five longitudinal twin cohorts from across the world and in different stages of the lifespan (N = 861). Heritability estimates of brain changes were significant and ranged from 16% (caudate) to 42% (cerebellar gray matter) for all global and most subcortical volumes (with the exception of thalamus and pallidum). Heritability estimates of change rates were generally higher in adults than in children suggesting an increasing influence of genetic factors explaining individual differences in brain structural changes with age. In children, environmental influences in part explained individual differences in developmental changes in brain structure. Multivariate genetic modeling showed that genetic influences of change rates and baseline volume significantly overlapped for many structures. The genetic influences explaining individual differences in the change rate for cerebellum, cerebellar gray matter and lateral ventricles were independent of the genetic influences explaining differences in their baseline volumes. These results imply the existence of genetic variants that are specific for brain plasticity, rather than brain volume itself. Identifying these genes may increase our understanding of brain development and ageing and possibly have implications for diseases that are characterized by deviant developmental trajectories of brain structure. Hum Brain Mapp 38:4444–4458, 2017. © 2017 Wiley Periodicals, Inc.     

Thalamic and amygdala-hippocampal volume reductions in first-degree relatives of patients with schizophrenia: an MRI-based morphometric analysis.

BACKGROUND: Schizophrenia is characterized by subcortical and cortical brain abnormalities. Evidence indicates that some nonpsychotic relatives of schizophrenic patients manifest biobehavioral abnormalities, including brain abnormalities. The goal of this study was to determine whether amygdala-hippocampal and thalamic abnormalities are present in relatives of schizophrenic patients. METHODS: Subjects were 28 nonpsychotic, and nonschizotypal, first-degree adult relatives of schizophrenics and 26 normal control subjects. Sixty contiguous 3 mm coronal, T1-weighted 3D magnetic resonance images of the brain were acquired on a 1.5 Tesla magnet. Cortical and subcortical gray and white matter and cerebrospinal fluid (CSF) were segmented using a semi-automated intensity contour mapping algorithm. Analyses of covariance of the volumes of brain regions, controlling for expected intellectual (i.e., reading) ability and diagnosis, were used to compare groups. RESULTS: The main findings were that relatives had significant volume reductions bilaterally in the amygdala-hippocampal region and thalamus compared to control subjects. Marginal differences were noted in the pallidum, putamen, cerebellum, and third and fourth ventricles. CONCLUSIONS: Results support the hypothesis that core components of the vulnerability to schizophrenia include structural abnormalities in the thalamus and amygdala-hippocampus. These findings require further work to determine if the abnormalities are an expression of the genetic liability to schizophrenia.     

Decreased thalamic volumes in adolescent inhalant users from Korea and Australia

Objectives. Research investigating the impact of inhalant misuse on brain structure suggests abnormalities in subcortical regions. We investigated the association between inhalant misuse and subcortical brain volumes in adolescents. Methods. Based on a collaborative dataset from South Korea (inhalant users: N = 15, mean age = 16.7, SD = 1.1; controls: N = 15, mean age = 15.4, SD = 1.2) and Australia (inhalant users: N = 7, mean age = 18.2, SD = 1.4; controls: N = 7, mean age = 18.9, SD = 2.6), the volumes of caudate nucleus, putamen, pallidum, amygdala, hippocampus, and thalamus were estimated in adolescent inhalant users and healthy adolescents using FreeSurfer. Results. The results revealed a significantly decreased right thalamic volume in adolescent inhalant users (P = 0.042), along with a trend-level decrease in left thalamic volume (P = 0.061). A negative correlation (r = –0.544; P = 0.036) between thalamic volume and severity of inhalant use (i.e., reduced volumes associated with greater use) was identified among Korean participants. Conclusions. These findings suggest that compared with other subcortical structures, the thalamus is particularly sensitive to damage following chronic inhalant exposure during adolescence.     

Correlations between ventricular enlargement and gray and white matter volumes of cortex,thalamus, striatum,and internal capsule in schizophrenia

Ventricular enlargement is one of the most consistent abnormal structural brain findings in schizophrenia and has been used to infer brain shrinkage. However, whether ventricular enlargement is related to local overlying cortex and/or adjacent subcortical structures or whether it is related to brain volume change globally has not been assessed. We systematically assessed interrelations of ventricular volumes with gray and white matter volumes of 40 Brodmann areas (BAs), the thalamus and its medial dorsal nucleus and pulvinar, the internal capsule, caudate and putamen. We acquired structural MRI ( patients with schizophrenia (n = 64) and healthy controls (n = 56)) and diffusion tensor fractional anisotropy (FA) (untreated schizophrenia n = 19, controls n = 32). Volumes were assessed by manual tracing of central structures and a semi-automated parcellation of BAs. Patients with schizophrenia had increased ventricular size associated with decreased cortical gray matter volumes widely across the brain; a similar but less pronounced pattern was seen in normal controls; local correlations (e.g. temporal horn with temporal lobe volume) were not appreciably higher than non-local correlations (e.g. temporal horn with prefrontal volume). White matter regions adjacent to the ventricles similarly did not reveal strong regional relationships. FA and center of mass of the anterior limb of the internal capsule also appeared differentially influenced by ventricular volume but findings were similarly not regional. Taken together, these findings indicate that ventricular enlargement is globally interrelated with gray matter volume diminution but not directly correlated with volume loss in the immediately adjacent caudate, putamen, or internal capsule.     

Reduced caudate gray matter volume in women with major depressive disorder

Previous brain-imaging studies have reported that major depressive disorder (MDD) is characterized by decreased volumes of several cortical and subcortical structures, including the hippocampus, amygdala, anterior cingulate cortex, and caudate nucleus. The purpose of the present study was to identify structural volumetric differences between MDD and healthy participants using a method that allows a comparison of gray and white matter volume across the whole brain. In addition, we explored the relation between symptom severity and brain regions with decreased volumes in MDD participants. The study group comprised 22 women diagnosed with MDD and 25 healthy women with no history of major psychiatric disorders. Magnetic resonance brain images were analyzed using optimized voxel-based morphometry to examine group differences in regional gray and white matter volume. Compared with healthy controls, MDD participants were found to have decreased gray matter volume in the bilateral caudate nucleus and the thalamus. No group differences were found for white matter volume, nor were there significant correlations between gray matter volumes and symptom severity within the MDD group. The present results suggest that smaller volume of the caudate nucleus may be related to the pathophysiology of MDD and may account for abnormalities of the cortico-striatal-pallido-thalamic loop in MDD.     

Subcortical nuclei volumes in suicidal behavior: nucleus accumbens may modulate the lethality of acts.

Previously, studies have demonstrated cortical impairments in those who complete or attempt suicide. Subcortical nuclei have less often been implicated in the suicidal vulnerability. In the present study, we investigated, with a specific design in a large population, variations in the volume of subcortical structures in patients with mood disorders who have attempted suicide. We recruited 253 participants: 73 suicide attempters with a past history of both mood disorders and suicidal act, 89 patient controls with a past history of mood disorders but no history of suicidal act, and 91 healthy controls. We collected 1.5 T magnetic resonance imaging data from the caudate, pallidum, putamen, nucleus accumbens, hippocampus, amygdala, ventral diencephalon, and thalamus. Surface-based morphometry (Freesurfer) analysis was used to comprehensively evaluate gray matter volumes. In comparison to controls, suicide attempters showed no difference in subcortical volumes when controlled for intracranial volume. However, within attempters negative correlations between the left (r?=??0.35, p?=?0.002), and right (r?=??0.41, p?<?0.0005) nucleus accumbens volumes and the lethality of the last suicidal act were found. Our study found no differences in the volume of eight subcortical nuclei between suicide attempters and controls, suggesting a lack of association between these regions and suicidal behavior in general. However, individual variations in nucleus accumbens structure and functioning may modulate the lethality of suicidal acts during a suicidal crisis. The known role of nucleus accumbens in action selection toward goals determined by the prefrontal cortex, decision-making or mental pain processing are hypothesized to be potential explanations.     

Structural covariance in the cortex of very preterm adolescents: A voxel‐based morphometry study

On the basis of findings in normative samples that different cortical brain regions covary in gray matter volume, most likely as a result of mutually trophic influences during cortical development, we aimed to study whether patterns of covariation in regional gray matter, i.e., structural covariance, differed between adolescents who were born very preterm and full‐term controls. Optimized voxel‐based morphometry was used to study structural magnetic resonance imaging scans from 218 very preterm adolescents (gestational age <33 weeks) and 127 controls at 14–15 years of age. Local gray matter volumes were obtained for 18 regions of interest involved in sensorimotor and higher‐order cognitive functions. These were then used to predict local volumes in the remaining areas of the cortex, with total gray matter volume, age and gender used as confounding variables. Very preterm adolescents compared with controls demonstrated differential (i.e., both increased and decreased) structural covariance between medial, frontal and cingulate gyri, caudate nucleus, thalamus, primary visual cortex, cerebellum and several other cortical and subcortical regions of the cortex. These findings support previous research indicating that preterm birth is associated with altered cortical development, and suggest that developmental changes in one brain region may result in a cascade of alterations in multiple regions. Hum Brain Mapp, 2010. © 2010 Wiley‐Liss, Inc.     

Early developmental gene enhancers affect subcortical volumes in the adult human brain

Genome‐wide association screens aim to identify common genetic variants contributing to the phenotypic variability of complex traits, such as human height or brain morphology. The identified genetic variants are mostly within noncoding genomic regions and the biology of the genotype–phenotype association typically remains unclear. In this article, we propose a complementary targeted strategy to reveal the genetic underpinnings of variability in subcortical brain volumes, by specifically selecting genomic loci that are experimentally validated forebrain enhancers, active in early embryonic development. We hypothesized that genetic variation within these enhancers may affect the development and ultimately the structure of subcortical brain regions in adults. We tested whether variants in forebrain enhancer regions showed an overall enrichment of association with volumetric variation in subcortical structures of >13,000 healthy adults. We observed significant enrichment of genomic loci that affect the volume of the hippocampus within forebrain enhancers (empirical P = 0.0015), a finding which robustly passed the adjusted threshold for testing of multiple brain phenotypes (cutoff of P < 0.0083 at an alpha of 0.05). In analyses of individual single nucleotide polymorphisms (SNPs), we identified an association upstream of the ID2 gene with rs7588305 and variation in hippocampal volume. This SNP‐based association survived multiple‐testing correction for the number of SNPs analyzed but not for the number of subcortical structures. Targeting known regulatory regions offers a way to understand the underlying biology that connects genotypes to phenotypes, particularly in the context of neuroimaging genetics. This biology‐driven approach generates testable hypotheses regarding the functional biology of identified associations. Hum Brain Mapp 37:1788–1800, 2016. © 2016 Wiley Periodicals, Inc .     

Genetic patterns of correlation among subcortical volumes in humans: Results from a magnetic resonance imaging twin study

Little is known about genetic influences on the volume of subcortical brain structures in adult humans, particularly whether there is regional specificity of genetic effects. Understanding patterns of genetic covariation among volumes of subcortical structures may provide insight into the development of individual differences that have consequences for cognitive and emotional behavior and neuropsychiatric disease liability. We measured the volume of 19 subcortical structures (including brain and ventricular regions) in 404 twins (110 monozygotic and 92 dizygotic pairs) from the Vietnam Era Twin Study of Aging and calculated the degree of genetic correlation among these volumes. We then examined the patterns of genetic correlation through hierarchical cluster analysis and by principal components analysis. We found that a model with four genetic factors best fit the data: a Basal Ganglia/Thalamus factor; a Ventricular factor; a Limbic factor; and a Nucleus Accumbens factor. Homologous regions from each hemisphere loaded on the same factors. The observed patterns of genetic correlation suggest the influence of multiple genetic influences. There is a genetic organization among structures which distinguishes between brain and cerebrospinal fluid spaces and between different subcortical regions. Further study is needed to understand this genetic patterning and whether it reflects influences on early development, functionally dependent patterns of growth or pruning, or regionally specific losses due to genes involved in aging, stress response, or disease. Hum Brain Mapp, 2011. © 2010 Wiley‐Liss, Inc.     

Wellbeing and brain structure: A comprehensive phenotypic and genetic study of image‐derived phenotypes in the UK Biobank

Wellbeing, an important component of mental health, is influenced by genetic and environmental factors. Previous association studies between brain structure and wellbeing have typically focused on volumetric measures and employed small cohorts. Using the UK Biobank Resource, we explored the relationships between wellbeing and brain morphometrics (volume, thickness and surface area) at both phenotypic and genetic levels. The sample comprised 38,982 participants with neuroimaging and wellbeing phenotype data, of which 19,234 had genotypes from which wellbeing polygenic scores (PGS) were calculated. We examined the association of wellbeing phenotype and PGS with all brain regions (including cortical, subcortical, brainstem and cerebellar regions) using multiple linear models, including (1) basic neuroimaging covariates and (2) additional demographic factors that may synergistically impact wellbeing and its neural correlates. Genetic correlations between genomic variants influencing wellbeing and brain structure were also investigated. Small but significant associations between wellbeing and volumes of several cerebellar structures (β = 0.015–0.029, P _FDR = 0.007–3.8 × 10⁻⁹), brainstem, nucleus accumbens and caudate were found. Cortical associations with wellbeing included volume of right lateral occipital, thickness of bilateral lateral occipital and cuneus, and surface area of left superior parietal, supramarginal and pre‐/post‐central regions. Wellbeing‐PGS was associated with cerebellar volumes and supramarginal surface area. Small mediation effects of wellbeing phenotype and PGS on right VIIIb cerebellum were evident. No genetic correlation was found between wellbeing and brain morphometric measures. We provide a comprehensive overview of wellbeing‐related brain morphometric variation. Notably, small effect sizes reflect the multifaceted nature of this concept.     

Cerebral structure on MRI, Part I: Localization of age-related changes

In this report, earlier findings of age-related changes in brain morphology on magnetic resonance (MR) images are extended to include measurements of individual cerebral grey matter structures and an index of white matter degeneration. Volumes of caudate, lenticular, and diencephalic structures are estimated, as are grey matter volumes in eight separate cortical regions. Results suggest that between 30 and 79 years significant decreases occur in the volume of the caudate nucleus, in anterior diencephalic structures, and in the grey matter of most cortical regions. The data suggest that the volumes of the thalamus and the anterior cingulate cortex may be unchanged. Among those cortical regions found to be affected in aging, some evidence is present for greater change in association cortices and mesial temporal lobe structures. There are also dramatic age-related changes in the white matter, manifest as lengthened T2 values on MR images.     

Brain structure and organization five decades after childhood onset epilepsy

The purpose of this project was to characterize brain structure and organization in persons with active and remitted childhood onset epilepsy 50 years after diagnosis compared with healthy controls. Participants from a population‐based investigation of uncomplicated childhood onset epilepsy were followed up 5 decades later. Forty‐one participants had a history of childhood onset epilepsy (mean age of onset = 5.2 years, current chronological age = 56.0 years) and were compared with 48 population‐based controls (mean age = 55.9 years). Of the epilepsy participants, 8 had persisting active epilepsy and in 33 the epilepsy had remitted. All participants underwent 3T MRI with subsequent vertex analysis of cortical volume, thickness, surface area and gyral complexity. In addition, cortical and subcortical volumes, including regions of the frontal, parietal, temporal, and occipital lobes, and subcortical structures including amygdala, thalamus, and hippocampus, were analyzed using graph theory techniques. There were modest group differences in traditional vertex‐based analyses of cortical volume, thickness, surface area and gyral index, as well as across volumes of subcortical structures, after correction for multiple comparisons. Graph theory analyses revealed suboptimal topological structural organization with enhanced network segregation and reduced global integration in the epilepsy participants compared with controls, these patterns significantly more extreme in the active epilepsy group. Furthermore, both groups with epilepsy presented a greater number of higher Z‐score regions in betweenness centrality (BC) than lower Z‐score regions compared with controls. Also, contrary to the group with remitted epilepsy, patients with active epilepsy presented most of their high BC Z‐score regions in subcortical areas including the amygdala, thalamus, hippocampus, pallidum, and accumbens. Overall, this population‐based investigation of long term outcome (5 decades) of childhood onset epilepsy reveals persisting abnormalities, especially when examined by graph theoretical measurements, and provides new insights into the very long‐term outcomes of active and remitted epilepsy. Hum Brain Mapp 38:3289–3299, 2017. © 2017 Wiley Periodicals, Inc.     

Genetic scores for adult subcortical volumes associate with subcortical volumes during infancy and childhood

Individual differences in subcortical brain volumes are highly heritable. Previous studies have identified genetic variants that underlie variation in subcortical volumes in adults. We tested whether those previously identified variants also affect subcortical regions during infancy and early childhood. The study was performed within the Generation R study, a prospective birth cohort. We calculated polygenic scores based on reported GWAS for volumes of the accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen, and thalamus. Participants underwent cranial ultrasound around 7 weeks of age (range: 3–20), and we obtained metrics for the gangliothalamic ovoid, a predecessor of the basal ganglia. Furthermore, the children participated in a magnetic resonance imaging (MRI) study around the age of 10 years (range: 9–12). A total of 340 children had complete data at both examinations. Polygenic scores primarily associated with their corresponding volumes at 10 years of age. The scores also moderately related to the diameter of the gangliothalamic ovoid on cranial ultrasound. Mediation analysis showed that the genetic influence on subcortical volumes at 10 years was only mediated for 16.5–17.6% of the total effect through the gangliothalamic ovoid diameter at 7 weeks of age. Combined, these findings suggest that previously identified genetic variants in adults are relevant for subcortical volumes during early life, and that they affect both prenatal and postnatal development of the subcortical regions.     

Volumetric measurements of subcortical nuclei in patients with temporal lobe epilepsy.

OBJECTIVE: To determine the volumes of subcortical nuclei in patients with chronic epilepsy. BACKGROUND: Animal and human data suggest a crucial role for subcortical structures in the modulation of seizure activity, mostly as seizure-suppressing relays. Although cortical epileptogenic foci can vary in localization and extent, it nevertheless appears that these structures subsequently influence seizure propagation in a universal fashion. There is, however, little knowledge about the size of implicated subcortical structures in patients with epilepsy. METHOD: Using high-resolution MRI, the volumes of selected subcortical nuclei, such as the thalamus, caudate nucleus, putamen, and pallidum, were measured in both hemispheres of 27 patients with temporal lobe epilepsy. Fourteen healthy volunteers served as controls. Statistical analysis was done for both normalized volumes (by total brain volume) and unnormalized volumes. RESULTS: Overall, the patient group had smaller thalamic and striatal volumes in both hemispheres, mostly ipsilateral to the epileptic focus. No significant correlations were noted between volume measurements and age, age at onset, duration of epilepsy, or total seizure frequency, including frequency of generalized seizures. The putamen and thalamus seemed to be affected predominantly in patients with a history of febrile convulsions, whereas patients without febrile convulsions had smaller caudate nuclei bilaterally. CONCLUSIONS: Volumetric measurements of subcortical nuclei reveal atrophy of distinct subcortical nuclei in the patient group, predominantly ipsilateral to the focus. This finding probably reflects persistent abnormalities and not secondary change. In addition, the structural differences between patients with and patients without previous febrile convulsions suggest that these conditions may have different causes.     

White matter abnormalities in gene‐positive myoclonus‐dystonia

Myoclonus‐dystonia is an autosomal dominantly inherited movement disorder clinically characterized by myoclonic jerks and dystonic movements of the upper body. Functional imaging and structural gray matter imaging studies in M‐D suggest defective sensorimotor integration and an association between putaminal volume and severity of dystonia, possibly because of neuronal plasticity. As we expect changes in the connections between the cortical and subcortical regions, we performed a combination of white matter voxel‐based morphometry (wVBM) and diffusion tensor imaging (DTI) to detect macro‐ and microstructural white matter changes, respectively, in DYT‐11 mutations carriers (M‐D). Sixteen clinically affected DYT‐11 mutation carriers and 18 control subjects were scanned with 3‐Tesla MRI to compare white matter volume, fractional anisotropy, and mean diffusivity between groups. In DYT11 mutation carriers, increased white matter volume and FA and decreased mean diffusivity werefound in the subthalamic area of the brain stem, including the red nucleus. Furthermore, decreased mean diffusivity was found in the subgyral cortical sensorimotor areas. The white matter changes found in the subthalamic area of the brain stem, connecting the cerebellum with the thalamus, are compatible with the hypothesis that abnormal function in M‐D involves a network that includes the cerebellum, brain stem, and basal ganglia. Whether these changes are causative or an effect of M‐D requires further study. © 2012 Movement Disorder Society     

Involvement of the thalamocortical network in TLE with and without mesiotemporal sclerosis

Purpose: The thalamus plays an important role in seizure propagation in temporal lobe epilepsy (TLE). This study investigated how structural abnormalities in the focus, ipsilateral thalamus and extrafocal cortical structures relate to each other in TLE with mesiotemporal sclerosis (TLE‐MTS) and without hippocampal sclerosis (TLE‐no). Methods: T₁ and high‐resolution T₂ images were acquired on a 4T magnet in 29 controls, 15 TLE‐MTS cases, and 14 TLE‐no. Thalamus volumes were obtained by warping a labeled atlas onto each subject’s brain. Deformation‐based morphometry was used to identify regions of thalamic volume loss and FreeSurfer for cortical thickness measurements. CA1 volumes were obtained from high‐resolution T₂ images. Multiple regression analysis and correlation analyses for voxel‐ and vertex‐based analyses were performed in SPM2 and FreeSurfer. Results: TLE‐MTS had bilateral volume loss in the anterior thalamus, which was correlated with CA1 volume and cortical thinning in the mesiotemporal lobe. TLE‐no had less severe volume loss in the dorsal lateral nucleus, which was correlated with thinning in the mesiotemporal region but not with extratemporal thinning. Discussion: The findings suggest that seizure propagation from the presumed epileptogenic focus or regions close to it into the thalamus occurs in TLE‐MTS and TLE‐no and results in circumscribed neuronal loss in the thalamus. However, seizure spread beyond the thalamus seems not to be responsible for the extensive extratemporal cortical abnormalities in TLE.     

Effects of cannabis and familial loading on subcortical brain volumes in first-episode schizophrenia

Schizophrenia is a severe neuropsychiatric disorder with familial loading as heritable risk factor and cannabis abuse as the most relevant environmental risk factor up to date. Cannabis abuse has been related to an earlier onset of the disease and persisting cannabis consumption is associated with reduced symptom improvement. However, the underlying morphological and biochemical brain alterations due to these risk factors as well as the effects of gene-environmental interaction are still unclear. In this magnetic resonance imaging (MRI) study in 47 first-episode schizophrenia patients and 30 healthy control subjects, we investigated effects of previous cannabis abuse and increased familial risk on subcortical brain regions such as hippocampus, amygdala, caudate nucleus, putamen, thalamus and subsegments of the corpus callosum (CC). In a subsequent single-volume ¹H-magnetic resonance spectroscopy study, we investigated spectra in the left hippocampus and putamen to detect metabolic alterations. Compared to healthy controls, schizophrenia patients displayed decreased volumes of the left hippocampus, bilateral amygdala and caudate nucleus as well as an increased area of the midsagittal CC1 segment of the corpus callosum. Patients fulfilling the criteria for cannabis abuse at admission showed an increased area of the CC2 segment compared to those who did not fulfill the criteria. Patients with a family history of schizophrenia combined with previous cannabis abuse showed lower volumes of the bilateral caudate nucleus compared to all other patients, implicating an interaction between the genetic background and cannabis abuse as environmental factor. Patients with cannabis abuse also had higher ratios of N-acetyl aspartate/choline in the left putamen, suggesting a possible neuroprotective effect in this area. However, antipsychotic medication prior to MRI acquisition and gender effects may have influenced our results. Future longitudinal studies in first-episode patients with quantification of cannabis abuse and assessment of schizophrenia risk genes are warranted.

     

Volume reduction in subcortical regions according to severity of Alzheimer’s disease

We investigated whether there exists a hierarchical vulnerability of subcortical structures with respect to the severity of Alzheimer’s disease (AD). A total of 236 subjects (179 with AD and 57 with normal cognition) underwent 1.5-T magnetic resonance (MR) imaging. The volumes of the five subcortical structures (amygdala, thalamus, putamen, globus pallidus, and caudate nucleus) and hippocampus were analyzed using a large deformation diffeomorphic metric mapping algorithm. The volume changes were evaluated according to the Clinical Dementia Rating (CDR). Correlation between the volumes of the subcortical structures and scores of the cognitive domain-specific neuropsychological tests were evaluated. Volume loss of the amygdala occurred even in the very mild stage of AD (CDR 0.5), as did volume loss in the hippocampus. Similar reductions in volume occurred in the thalamus and putamen, however during the mild (CDR 1) and moderate (CDR 2) stages of AD, respectively. The globus pallidus and caudate nucleus remained devoid of changes until the moderate stage of AD (p < 0.01). Volume loss in those subcortical structures correlated with the neuropsychological test scores (p < 0.01). Our results suggest that there is a hierarchical vulnerability in subcortical structures according to the clinical severity of AD and that subcortical volume reductions correlate with cognitive impairment.