Development and heritability of subcortical brain volumes at ages 9 and 12

Subcortical brain structures are involved in a variety of cognitive and emotional functions and follow different trajectories of increase and decrease in volume from childhood to adulthood. The heritability of development of subcortical brain volumes during adolescence has not been studied comprehensively. In a longitudinal twin study, we estimated to what extent subcortical brain volumes are influenced by genetic factors at ages 9 and 12. In addition, we assessed whether new genes are expressed at age 12 and whether there is evidence for genotype by sex interaction. Brain scans were acquired for 112 and 89 twin pairs at 9 and 12 years of age. In both boys and girls, there was an increase in volumes of the thalamus, hippocampus, amygdala and pallidum, and a decrease in volumes of the caudate and nucleus accumbens. The putamen showed a decrease in boys bilaterally and an increase in girls in the left hemisphere. Heritability was high (>50%) for all structures – except for the left nucleus accumbens – with heritabilities ranging from 0.50 to 0.91 at age 9, and from 0.59 to 0.88 at age 12. There were no significant new genetic effects coming into play at age 12, and there was no evidence for genotype by sex interactions. These findings suggest that despite their sensitivity to environmental effects, the heritability of subcortical brain structures is high from childhood on, resembling estimates found in adult samples.     

Grey Matter Atrophy in Multiple Sclerosis: Clinical Interpretation Depends on Choice of Analysis Method

Background

Studies disagree on the location of grey matter (GM) atrophy in the multiple sclerosis (MS) brain.

Aim

To examine the consistency between FSL, FreeSurfer, SPM for GM atrophy measurement (for volumes, patient/control discrimination, and correlations with cognition).

Materials and Methods

127 MS patients and 50 controls were included and cortical and deep grey matter (DGM) volumetrics were performed. Consistency of volumes was assessed with Intraclass Correlation Coefficient/ICC. Consistency of patients/controls discrimination was assessed with Cohen’s d, t-tests, MANOVA and a penalized double-loop logistic classifier. Consistency of association with cognition was assessed with Pearson correlation coefficient and ANOVA. Voxel-based morphometry (SPM-VBM and FSL-VBM) and vertex-wise FreeSurfer were used for group-level comparisons.

Results

The highest volumetry ICC were between SPM and FreeSurfer for cortical regions, and the lowest between SPM and FreeSurfer for DGM. The caudate nucleus and temporal lobes had high consistency between all software, while amygdala had lowest volumetric consistency. Consistency of patients/controls discrimination was largest in the DGM for all software, especially for thalamus and pallidum. The penalized double-loop logistic classifier most often selected the thalamus, pallidum and amygdala for all software. FSL yielded the largest number of significant correlations. DGM yielded stronger correlations with cognition than cortical volumes. Bilateral putamen and left insula volumes correlated with cognition using all methods.

Conclusion

GM volumes from FreeSurfer, FSL and SPM are different, especially for cortical regions. While group-level separation between MS and controls is comparable, correlations between regional GM volumes and clinical/cognitive variables in MS should be cautiously interpreted.     

Genetic architecture of subcortical brain regions: common and region‐specific genetic contributions

Understanding the aetiology of patterns of variation within and covariation across brain regions is key to advancing our understanding of the functional, anatomical and developmental networks of the brain. Here we applied multivariate twin modelling and principal component analysis (PCA) to investigate the genetic architecture of the size of seven subcortical regions (caudate nucleus, thalamus, putamen, pallidum, hippocampus, amygdala and nucleus accumbens) in a genetically informative sample of adolescents and young adults (N = 1038; mean age = 21.6 ± 3.2 years; including 148 monozygotic and 202 dizygotic twin pairs) from the Queensland Twin IMaging (QTIM) study. Our multivariate twin modelling identified a common genetic factor that accounts for all the heritability of intracranial volume (0.88) and a substantial proportion of the heritability of all subcortical structures, particularly those of the thalamus (0.71 out of 0.88), pallidum (0.52 out of 0.75) and putamen (0.43 out of 0.89). In addition, we also found substantial region‐specific genetic contributions to the heritability of the hippocampus (0.39 out of 0.79), caudate nucleus (0.46 out of 0.78), amygdala (0.25 out of 0.45) and nucleus accumbens (0.28 out of 0.52). This provides further insight into the extent and organization of subcortical genetic architecture, which includes developmental and general growth pathways, as well as the functional specialization and maturation trajectories that influence each subcortical region.     

Reduced Hippocampal Volume in Healthy Young ApoE4 Carriers: An MRI Study

The E4 allele of the ApoE gene has consistently been shown to be related to an increased risk of Alzheimer''s disease (AD). The E4 allele is also associated with functional and structural grey matter (GM) changes in healthy young, middle-aged and older subjects. Here, we assess volumes of deep grey matter structures of 22 healthy younger ApoE4 carriers and 22 non-carriers (20–38 years). Volumes of the nucleus accumbens, amygdala, caudate nucleus, hippocampus, pallidum, putamen, thalamus and brain stem were calculated by FMRIB''s Integrated Registration and Segmentation Tool (FIRST) algorithm. A significant drop in volume was found in the right hippocampus of ApoE4 carriers (ApoE4+) relative to non-carriers (ApoE4−), while there was a borderline significant decrease in the volume of the left hippocampus of ApoE4 carriers. The volumes of no other structures were found to be significantly affected by genotype. Atrophy has been found to be a sensitive marker of neurodegenerative changes, and our results show that within a healthy young population, the presence of the ApoE4+ carrier gene leads to volume reduction in a structure that is vitally important for memory formation. Our results suggest that the hippocampus may be particularly vulnerable to further degeneration in ApoE4 carriers as they enter middle and old age. Although volume reductions were noted bilaterally in the hippocampus, atrophy was more pronounced in the right hippocampus. This finding relates to previous work which has noted a compensatory increase in right hemisphere activity in ApoE4 carriers in response to preclinical declines in memory function. Possession of the ApoE4 allele may lead to greater predilection for right hemisphere atrophy even in healthy young subjects in their twenties.     

Role of the caudate nucleus in the development of evoked synchronized activity

Synchronized activity (spindles, augmentation response) evoked by stimulation of thalamic nonspecific, association, and specific nuclei was investigated in chronic experiments on 11 cats before and after successive destruction of the caudate nuclei. After destruction of the caudate nuclei the duration of spindle activity in the frontal cortex and subcortical formations (thalamic nuclei, globus pallidus, putamen) was reduced to only three or four oscillations. In the subcortical nuclei its amplitude fell significantly (by 50±10%); in the cortex the decrease in amplitude was smaller and in some cases was not significant. Different changes were observed in the amplitude of the augmentation response, depending on where it was recorded. In the subcortical formations it was considerably and persistently reduced (by 50±10%); in the cortex these changes were unstable in character. Unilateral destruction of the caudate nucleus inhibited synchronized activity evoked by stimulation of the thalamic nuclei on the side of the operation only. Destruction of the basal ganglia (caudate nucleus, globus pallidus, entopeduncular nucleus, and putamen) did not prevent the appearance of synchronized activity; just as after isolated destruction of the caudate nucleus, after this operation synchronized activity was simply reduced in duration and amplitude. It is suggested that the caudate nucleus exerts an ipsilateral facilitatory influence on the nonspecific system of the thalamus during the development of evoked synchronized activity.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 9, No. 3, pp. 239–248, May–June, 1977.     

Age-Related Differences and Relationships Between Elements in Human Amygdala and Other Limbic System or Basal Ganglia

To elucidate the compositional changes of the amygdala with aging, the authors investigated age-related differences of elements in human amygdalae. In addition, the relationships between the amygdala and other brain regions were investigated from a viewpoint of elements. After ordinary dissections at Nara Medical University were finished, the amygdalae were removed from the cerebra of the subjects who consisted of 22 men and 23 women, ranging in age from 70 to 101 years. In addition, the hippocampus, dentate gyrus, mammillary body of the limbic system and the caudate nucleus, putamen, and globus pallidus of the basal ganglia were also removed from the identical cerebra. After the brain samples were incinerated with nitric acid and perchloric acid, the element contents were determined by inductively coupled plasma-atomic emission spectrometry. It was found that both the Ca and Mg contents increased significantly in the amygdalae with aging, but the other five element contents (P, S, Zn, Fe, and Na) did not change significantly in the amygdalae with aging. Regarding the relationships among elements, very significant or significant direct correlations were found among the Ca, P, and Mg contents in the amygdalae. To explore the relationships between the amygdala and either other limbic system or basal ganglia, the correlations between seven elements of the amygdala and hippocampus, dentate gyrus, or mammillary body, and between those of the amygdala and caudate nucleus, putamen, or globus pallidus which derived from the identical cerebra, were analyzed with Pearson’s correlation. It was found that regarding the four elements of Ca, P, Mg, and Fe, a close relationship existed between the amygdala and hippocampus, globus pallidus, or mammillary body.     

Altered Muscarinic and Nicotinic Receptor Densities in Cortical and Subcortical Brain Regions in Parkinson's Disease

Abstract: Muscarinic and nicotinic cholinergic receptors and choline acetyltransferase activity were studied in postmortem brain tissue from patients with histopathologically confirmed Parkinson's disease and matched control subjects. Using washed membrane homogenates from the frontal cortex, hippocampus, caudate nucleus, and putamen, saturation analysis of specific receptor binding was performed for the total number of muscarinic receptors with [³H]quinuclidinyl benzilate, for muscarinic M₁ receptors with [³H]pirenzepine, for muscarinic M₂ receptors with [³H]oxotremorine-M, and for nicotinic receptors with (–)-[³H]nicotine. In comparison with control tissues, choline acetyltransferase activity was reduced in the frontal cortex and hippocampus and unchanged in the caudate nucleus and putamen of parkinsonian patients. In Parkinson's disease the maximal binding site density for [³H]quinuclidinyl benzilate was increased in the frontal cortex and unaltered in the hippocampus, caudate nucleus, and putamen. Specific [³H]pirenzepine binding was increased in the frontal cortex, unaltered in the hippocampus, and decreased in the caudate nucleus and putamen. In parkinsonian patients B_max values for specific [³H]oxotremorine-M binding were reduced in the cortex and unchanged in the hippocampus and striatum compared with controls. Maximal (–)-[³H]nicotine binding was reduced in both the cortex and hippocampus and unaltered in both the caudate nucleus and putamen. Alterations of the equilibrium dissociation constant were not observed for any ligand in any of the brain areas examined. The present results suggest that both the innominatocortical and the septohippocampal cholinergic systems degenerate in Parkinson's disease. The reduction of cortical [³H]oxotremorine-M and (–)-[³H]nicotine binding is compatible with the concept that significant numbers of the binding sites labelled by these ligands are located on presynaptic cholinergic nerve terminals, whereas the increased [³H]pirenzepine binding in the cortex may reflect postsynaptic denervation supersensitivity.     

Biochemical Characterization of α-Adrenergic Receptors in Human Brain and Changes in Alzheimer-Type Dementia

Abstract Using ligand binding techniques, we studied α-adrenergic receptors in brains obtained at autopsy from seven histologically normal controls and seven patients with histopathologically verified Alzheimer-type dementia (ATD). Binding of the α-adrenergic antagonists [³H]prazosin and [³H]yohimbine to membranes of human brains exhibited characteristics compatible with α₁- and α₂-adrenergic receptors, respectively. Binding of both ligands was saturable and reversible, with dissociation constants of 0.15 nM for [³H]prazosin and 5.5 nM for [³H]yohimbine. [³H]Prazosin binding was highest in the hippocampus and frontal cortex and lowest in the caudate and putamen in the control brains. [³H]Yohimbine binding was highest in the nucleus basalis of Meynert (NbM) and frontal cortex and lowest in the caudate and cerebellar hemisphere in the control brains. Compared with values for the controls, [³H]prazosin binding sites were significantly reduced in number in the hippocampus and cerebellar hemisphere, and [³H]yohimbine binding sites were significantly reduced in number in the NbM in the ATD brains. These results suggest that α₁ and α₂-adrenergic receptors are present in the human brain and that there are significant changes in numbers of both receptors in selected regions in patients with ATD.     

Reward‐related ventral striatum reactivity mediates gender‐specific effects of a galanin remote enhancer haplotype on problem drinking

The neuropeptide galanin has been implicated in the regulation of appetitive and consummatory behaviors. Prior studies have shown that direct injection of galanin into the hypothalamus results in increased release of dopamine (DA) in the nucleus accumbens (NAcc), and parallel increases in food and alcohol consumption. These studies are consistent with a role of hypothalamic galanin in regulating reward system reactivity. In humans, a common functional haplotype (GAL5.1) within a remote enhancer region upstream of the galanin gene (GAL) affects promoter activity and galanin expression in hypothalamic neurons in vitro. Given the effects of hypothalamic galanin on NAcc DA release and the effects of the GAL5.1 haplotype on GAL expression, we examined the impact of this functional genetic variation on human reward‐related ventral striatum (VS) reactivity. Using an imaging genetics strategy in Caucasian individuals (N = 138, 72 women) participating in the ongoing Duke Neurogenetics Study, we report a significant gender‐by‐genotype interaction (right hemisphere: F_1,134 = 8.08, P = 0.005; left hemisphere: F_1,134 = 5.39, P = 0.022), such that homozygosity for the GG haplotype, which predicts greater GAL expression, is associated with relatively increased VS reactivity in women (n = 50, right hemisphere: P = 0.015; left hemisphere: P = 0.060), but not in men (N = 49, P‐values > 0.10). Furthermore, these differences in VS reactivity correlated positively with differences in alcohol use, such that VS reactivity mediated a gender‐specific association between GAL5.1 haplotype and problem drinking. Our current results support those in animal models implicating galanin signaling in neural pathways associated with appetitive and consummatory behaviors of relevance for understanding risk for substance use and abuse.     

Brain Activity Changes in Cognitive Networks in Relapsing-Remitting Multiple Sclerosis – Insights from a Longitudinal fMRI Study

Background

Extrapolations from previous cross-sectional fMRI studies suggest cerebral functional changes with progression of Multiple Sclerosis (MS), but longitudinal studies are scarce. We assessed brain activation changes over time in MS patients using a cognitive fMRI paradigm and examined correlations with clinical and cognitive status and brain morphology.

Methods

13 MS patients and 15 healthy controls (HC) underwent MRI including fMRI (go/no-go task), neurological and neuropsychological exams at baseline (BL) and follow-up (FU; minimum 12, median 20 months). We assessed estimates of and changes in fMRI activation, total brain and subcortical grey matter volumes, cortical thickness, and T2-lesion load. Bland-Altman (BA) plots served to assess fMRI signal variability.

Results

Cognitive and disability levels remained largely stable in the patients. With the fMRI task, both at BL and FU, patients compared to HC showed increased activation in the insular cortex, precuneus, cerebellum, posterior cingulate cortex, and occipital cortex. At BL, patients vs. HC also had lower caudate nucleus, thalamus and putamen volumes. Over time, patients (but not HC) demonstrated fMRI activity increments in the left inferior parietal lobule. These correlated with worse single-digit-modality test (SDMT) performance. BA-plots attested to reproducibility of the fMRI task. In the patients, the right caudate nucleus decreased in volume which again correlated with worsening SDMT performance.

Conclusions

Given preserved cognitive performance, the increased activation at BL in the patients may be viewed as largely adaptive. In contrast, the negative correlation with SDMT performance suggests increasing parietal activation over time to be maladaptive. Several areas with purported relevance for cognition showed decreased volumes at BL and right caudate nucleus volume decline correlated with decreasing SDMT performance. This highlights the dynamics of functional changes and the strategic importance of specific brain areas for cognitive processes in MS.     

Mineral Composition of and the Relationships Between Them of Human Basal Ganglia in Very Old Age

Trace elements and the relationships among them were investigated by direct chemical analysis in three basal ganglia regions in very old age individuals and age- and gender-related differences were assessed. After ordinary dissections at Nara Medical University were finished, the caudate nucleus, putamen, and globus pallidus belonging to the basal ganglia were removed from the identical cerebra of the subjects who consisted of 22 men and 23 women, ranging in age from 70 to 101 years (average age?=?83.3?±?7.5 years). After incineration with nitric acid and perchloric acid, the element contents were determined by inductively coupled plasma-atomic emission spectrometry. It was found that the Ca, P, and Mg contents increased significantly in the putamen with aging and the Mg content increased significantly in the globus pallidus with aging, but no elements increased significantly in the caudate nucleus with aging. Regarding the relationships among elements in the basal ganglia, extremely significant direct correlations were found among the Ca, P, and Mg contents in the putamen. These results suggested that slight calcification occurred in the putamen in very old age. With regard to seven elements of Ca, P, S, Mg, Zn, Fe, and Na, it was examined whether there were significant correlations among the caudate nucleus, putamen, and globus pallidus. It was found that there were extremely significant direct correlations among all of the three basal ganglia in the P content. Likewise, with regard to the Fe content, there were extremely or very significant direct correlations among all of the three basal ganglia. Regarding the gender difference in elements, it was found that the Ca content of the caudate nucleus was significantly higher in women than in men.     

Family income buffers the relationship between childhood adverse experiences and putamen volume

Adverse experiences and family income in childhood have been associated with altered brain development. While there is a large body of research examining these associations, it has primarily used cross-sectional data sources and studied adverse experiences and family income in isolation. However, it is possible that low family income and adverse experiences represent dissociable and potentially interacting profiles of risk. To address this gap in the literature, we examined brain structure as a function of adverse experiences in childhood and family income in 158 youths with up to five waves of MRI data. Specifically, we assessed the interactive effect of these two risk factors on six regions of interest: hippocampus, putamen, amygdala, nucleus accumbens, caudate, and thalamus. Adverse experiences and family income interacted to predict putamen volume (B = 0.086, p = 0.011) but only in participants with family income one standard deviation below the mean (slope estimate = −0.11, p = 0.03). These results suggest that adverse experiences in childhood result in distinct patterns of brain development across the socioeconomic gradient. Given previous findings implicating the role of the putamen in psychopathology-related behaviors, these results emphasize the importance of considering life events and socioeconomic context when evaluating markers of risk. Future research should include interactive effects of environmental exposures and family income to better characterize risk for psychopathology in diverse samples.     

Cocaine regulates protein kinase B and glycogen synthase kinase-3 activity in selective regions of rat brain

Protein kinase B (also known as Akt) signaling regulates dopamine-mediated locomotor behaviors. Here the ability of cocaine to regulate Akt and glycogen synthase kinase 3 (GSK3) was studied. Rats were injected with cocaine or saline in a binge-pattern, which consisted of three daily injections of 15 mg/kg cocaine or 1 mL/kg saline spaced 1 h apart for 1, 3, or 14 days. Amygdala, nucleus accumbens, caudate putamen, and hippocampus tissues were dissected 30 min following the last injection and analyzed for phosphorylated and total Akt and GSK3(alpha and beta) protein levels using western blot analysis. Phosphorylation of Akt on the threonine-308 (Thr308) residue was significantly reduced in the nucleus accumbens and increased in the amygdala after 1 day of cocaine treatment; however, these effects were not accompanied by a significant decrease in GSK3 phosphorylation. Phosphorylation of Akt and GSK3 was significantly reduced after 14 days of cocaine administration, an effect that was only observed in the amygdala. Cocaine did not alter Akt or GSK3 phosphorylation in the caudate putamen or hippocampus. The findings in nucleus accumbens may reflect dopaminergic motor-stimulant activity caused by acute cocaine, whereas the effects in amygdala may be associated with changes in emotional state that occur after acute and chronic cocaine exposure.     

Increased apoptosis during neonatal brain development underlies the adult behavioral deficits seen in mice lacking a functional paternally expressed gene 3 (Peg3)

Inactivation of the maternally imprinted, paternally expressed gene 3 (Peg3) induces deficits in olfactory function, sexual and maternal behaviors, oxytocin neuron number, metabolic homeostasis and growth. Peg3 is expressed in a number of developing hypothalamic and basal forebrain structures and is a component of the P53 apoptosis pathway. Peg3 inactivation in neuronal cell culture lines inhibits P53 mediated apoptosis, which is important in the early postnatal development and sexual differentiation of the brain. In this study, we investigated the effect of inactivating the Peg3 gene on the incidence of caspase 3 positive cells (a marker of apoptosis) in 4‐ and 6‐day postpartum mouse brain. Inactivating the Peg3 gene resulted in an increase in the incidence of total forebrain caspase 3 positive cells at 4 and 6 days postpartum. Increases in specific neuroanatomical regions including the bed nucleus of the stria terminalis, nucleus accumbens, caudate putamen, medial pre‐optic area, arcuate nucleus, medial amygdala, anterior cortical and posteriodorsal amygdaloid nuclei, were also observed. In wild‐type mice, sex differences in the incidence of caspase 3 positive cells in the medial amygdala, bed nucleus of the stria terminalis, nucleus accumbens, arcuate nucleus and the M2 motor cortex, were also observed. This neural sex difference was ameliorated in the Peg‐3 mutant. These findings suggest that the neuronal and behavioral deficits seen in mice lacking a functional Peg3 gene are mediated by increases in the incidence of early neonatal apoptosis in neuroanatomical regions important for reproductive behavior, olfactory and pheromonal processing, thermoregulation and reward. © 2009 Wiley Periodicals, Inc. Develop Neurobiol, 2009     

Brain tissue volumes in familial longevity: the Leiden Longevity Study

Atrophy is one of the major age‐related changes in the brain. The absence of brain atrophy in elderly individuals reflects deceleration in the process of biological aging. Moreover, results from human twin studies suggest a large genetic influence on the variance of human brain tissue volumes. To investigate the association of brain volumes with exceptional longevity, we tested whether middle‐aged to elderly offspring of nonagenarian siblings have larger brain volumes than their spouses using magnetic resonance imaging. No differences in whole brain, gray matter and white matter volume were found. These brain volumes were associated with chronological age in offspring and control subjects (all P < 0.001). Left amygdalar volume of the offspring was larger (P = 0.03) compared with control subjects [mean volume offspring (cm³) (95% confidence interval, CI) = 1.39 (1.36–1.42), mean volume control subjects (cm³) (95% CI) = 1.32 (1.29–1.35)]. Association of left amygdalar volume with familial longevity was particularly pronounced when offspring with the oldest long‐lived parent were compared with control subjects (P = 0.01). Amygdalar volumes were not associated with chronological age in both groups. Our findings suggest that the observed association of a larger left amygdalar volume with familial longevity is not caused by a relative preservation of the left amygdala during the course of aging but most likely a result of early development caused by a genetic familial trait.     

Temporal characteristics of triggering dipole sources of the auditory <Emphasis Type="Italic">P</Emphasis>300 in tasks varying in complexity

The localization and the order of triggering of the equivalent dipole sources of the auditory evoked potential (AEP) P300 component were analyzed in healthy subjects performing tasks that required different degrees of concentration. The AEP P300 was isolated and analyzed in 12 subjects aged 18–23 years. The P300 was recorded via 19 channels in mono- and bimodal tasks using two- and three-stimulus methods of the oddball paradigm. Analysis of the equivalent dipole sources of the P300 component upon hearing sounds showed simultaneous activity of dipole sources located in the temporal areas of both hemispheres and in the right frontal area, as well as in the brainstem, irrespective of the task’s complexity. The counting of sounds in the monomodal task was accompanied by consecutive involvement of the left temporal, right temporal, and left frontal sources in the P300 generation; in the bimodal task, these were, respectively, the left parietal, right temporal and hippocampal, and left frontal sources.     

Distribution of Immunoreactive Prolyl Oligopeptidase in Human and Rat Brain

Prolyl oligopeptidase (POP) is a serine endoprotease that hydrolyses peptides shorter than 30-mer. POP may have a role in inositol 1,4,5-triphosphate (IP₃) signaling and in the actions of antidepressants, and POP inhibitors have exhibited antiamnesic and neuroprotective properties. However, little is known about the distribution of POP protein in the brain. We used immunohistochemistry to localize POP enzyme in the human whole hemisphere and in the rat whole brain. In humans, the highest POP densities were observed in caudate nucleus and putamen, hippocampus and cortex. In the rat, the highest POP densities were found in substantia nigra, hippocampus, cerebellum and caudate putamen. In general, the distribution of POP in human and rat brains was very similar and resembled that of IP₃ receptors. Our findings are support for a role of POP in movement regulation, cognition and possibly in IP₃ signaling. The expression of POP in processing nuclei further supports its function beyond neuropeptide metabolism. Dr. Erkki Tupala M.D. sadly passed away during the research project.     

Relationship between neurophysiological indices of cognitive processes and MRI characteristics of some brain structures in healthy subjects and patients with schizophrenia

The relationships between the parameters of waves of auditory event-related potentials (ERPs) in the oddball paradigm and the volumes of the hippocampus, amygdala, and caudate nuclei were analyzed in healthy subjects and patients with schizophrenia. The data obtained suggest that faster mental processes and stronger activation and/or synchronization of the activity of ERP wave generators in healthy subjects correspond to smaller volumes of the structures studied. The structure of the relationships in patients with schizophrenia differed from the normal one; significant correlations were observed with the volume of the caudate nuclei, and more pronounced “normalization” of neurophysiological characteristics was associated with large volumes of these structures.     

Brain and behaviour phenotyping of a mouse model of neurofibromatosis type‐1: an MRI/DTI study on social cognition

Neurofibromatosis type‐1 (NF1) is a common neurogenetic disorder and an important cause of intellectual disability. Brain‐behaviour associations can be examined in vivo using morphometric magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) to study brain structure. Here, we studied structural and behavioural phenotypes in heterozygous Nf1 mice (Nf1^+/?) using T2‐weighted imaging MRI and DTI, with a focus on social recognition deficits. We found that Nf1^+/? mice have larger volumes than wild‐type (WT) mice in regions of interest involved in social cognition, the prefrontal cortex (PFC) and the caudate‐putamen (CPu). Higher diffusivity was found across a distributed network of cortical and subcortical brain regions, within and beyond these regions. Significant differences were observed for the social recognition test. Most importantly, significant structure–function correlations were identified concerning social recognition performance and PFC volumes in Nf1^+/? mice. Analyses of spatial learning corroborated the previously known deficits in the mutant mice, as corroborated by platform crossings, training quadrant time and average proximity measures. Moreover, linear discriminant analysis of spatial performance identified 2 separate sub‐groups in Nf1^+/? mice. A significant correlation between quadrant time and CPu volumes was found specifically for the sub‐group of Nf1^+/? mice with lower spatial learning performance, suggesting additional evidence for reorganization of this region. We found strong evidence that social and spatial cognition deficits can be associated with PFC/CPu structural changes and reorganization in NF1.