Variation In Gray Matter Volume Research Articles

Structural neuroanatomy of human facial behaviors.

The human face plays a central role in emotions and social communication. The emotional and somatic motor networks generate facial behaviors, but whether facial behaviors have representations in the structural anatomy of the human brain is unknown. We coded 16 facial behaviors in 55 healthy older adults who viewed five videos that elicited emotions and examined whether individual differences in facial behavior were related to regional variation in gray matter volume. Voxel-based morphometry analyses revealed that greater emotional facial behavior during the disgust trial (i.e. greater brow furrowing and eye tightening as well as nose wrinkling and upper lip raising) and the amusement trial (i.e. greater smiling and eye tightening) was associated with larger gray matter volume in midcingulate cortex, supplementary motor area, and precentral gyrus, areas spanning both the emotional and somatic motor networks. When measured across trials, however, these facial behaviors (and others) only related to gray matter volume in the precentral gyrus, a somatic motor network hub. These findings suggest that the emotional and somatic motor networks store structural representations of facial behavior and that the midcingulate cortex is critical for generating the predictable movements in the face that arise during emotions.

Gray matter volume alterations in de novo Parkinson's disease: A mediational role in the interplay between sleep quality and anxiety.

Parkinson's disease (PD) is increasingly recognized for its non-motor symptoms, among which emotional disturbances and sleep disorders frequently co-occur. The commonality of neuroanatomical underpinnings for these symptoms is not fully understood. This study is intended to investigate the differences in gray matter volume (GMV) between PD patients with anxiety (A-PD) and those without anxiety (NA-PD). Additionally, it seeks to uncover the interplay between GMV variations and the manifestations of anxiety and sleep quality. A total of 37 A-PD patients, 43 NA-PD patients, and 36 healthy controls (HCs) were recruited, all of whom underwent voxel-based morphometry (VBM) analysis. Group differences in GMV were assessed using analysis of covariance (ANCOVA). Partial correlation between GMV, anxiety symptom, and sleep quality were analyzed. Mediation analysis explored the mediating role of the volume of GMV-distinct brain regions on the relationship between sleep quality and anxiety within the PD patient cohort. A-PD patients showed significantly lower GMV in the fusiform gyrus (FG) and right inferior temporal gyrus (ITG) compared to HCs and NA-PD patients. GMV in these regions correlated negatively with Hamilton Anxiety Rating Scale (HAMA) scores (right ITG: r = -0.690, p < 0.001; left FG: r = -0.509, p < 0.001; right FG: r = -0.576, p < 0.001) and positively with sleep quality in PD patients (right ITG: r = 0.592, p < 0.001; left FG: r = 0.356, p = 0.001; right FG: r = 0.470, p < 0.001). Mediation analysis revealed that GMV in the FG and right ITG mediated the relationship between sleep quality and anxiety symptoms, with substantial effect sizes accounted for by the right ITG (25.74%) and FG (left: 11.90%, right: 15.59%). This study has shed further light on the relationship between sleep disturbances and anxiety symptoms in PD patients. Given the pivotal roles of the FG and the ITG in facial recognition and the recognition of emotion-related facial expressions, our findings indicate that compromised sleep quality, under the pathological conditions of PD, may exacerbate the reduction in GMV within these regions, impairing the recognition of emotional facial expressions and thereby intensifying anxiety symptoms.

Challenges in replication: Does amygdala gray matter volume relate to social network size?

In this work, we tried to replicate and extend prior research on the relationship between social network size and the volume of the amygdala. We focused on the earliest evidence for this relationship (Bickart et al., Nature Neuroscience 14(2), 163–164, 2011) and another methodologically unique study that often is cited as a replication (Kanai et al., Proceedings of the Royal Society B: Biological Sciences, 279(1732), 1327–1334, 2012). Despite their tight link in the literature, we argue that Kanai et al. (Proceedings of the Royal Society B: Biological Sciences, 279(1732), 1327–1334, 2012) is not a replication of Bickart et al. Nature Neuroscience 14(2), 163–164 (2011), because it uses different morphometric measurements. We collected data from 128 participants on a 7-Tesla MRI and examined variations in gray matter volume (GMV) in the amygdala and its nuclei. We found inconclusive support for a correlation between measures of real-world social network and amygdala GMV, with small effect sizes and only anecdotal evidence for a positive relationship. We found support for the absence of a correlation between measures of online social network and amygdala GMV. We discuss different challenges faced in replication attempts for small effects, as initially reported in these two studies, and suggest that the results would be most helpful in the context of estimation and future meta-analytical efforts. Our findings underscore the value of a narrow approach in replication of brain-behavior relationships, one that is focused enough to investigate the specifics of what is measured. This approach can provide a complementary perspective to the more popular “thematic” alternative, in which conclusions are often broader but where conclusions may become disconnected from the evidence.

Altered Sexual Response-Related Functional Connectivity and Morphometric Changes Influenced by Sex Hormones across Menopausal Status.

Our study retrospectively investigated differential patterns of the functional connectivity (FC) of core brain regions synchronous with morphometric changes associated with sexual dysfunction in menopausal women, and their correlations with sexual hormones. Twenty-three premenopausal women (mean age: 41.52 ± 7.38 years) and 21 menopausal women (mean age: 55.52 ± 2.80 years) underwent sex hormone level measurements with high-resolution T1 and functional magnetic resonance imaging (MRI) during rest, neutral, and sexual arousal conditions. Analysis of covariance adjusted for age was used to compare the FC and gray matter (GM) volume between the two groups. Menopausal women showed lower GM volumes in the superior frontal gyrus (SFG), superior temporal pole, parahippocampal gyrus (PHG), hippocampus (Hip), amygdala (Amg), and cerebellum (Cb) compared to premenopausal women (p < 0.05). In addition, compared to premenopausal women, menopausal women showed decreased FC of seed regions involved in the SFG, frontal eye fields, and Amg, as well as target regions involved in the PHG, Hip, inferior frontal gyrus, Cb, and vermis (p < 0.005). Furthermore, the FC between the right Amg and right Cb and between the left Amg and right Cb during sexual arousal in both groups was positively correlated with total estrogen and estradiol levels, respectively (p < 0.01). The GM volume values in the right Amg and right Cb were positively correlated with total estrogen and estradiol levels (p < 0.05). Our study demonstrated an association between menopause-related differential FC and GM volume variations and fluctuating sex hormones. Our findings highlight that overlapping brain regions with functional alterations and morphometric changes are closely linked with menopausal symptom-related decreases in sexual arousal and hormone levels.

SLC25A24 gene methylation and gray matter volume in females with and without conduct disorder: an exploratory epigenetic neuroimaging study

Conduct disorder (CD), a psychiatric disorder characterized by a repetitive pattern of antisocial behaviors, results from a complex interplay between genetic and environmental factors. The clinical presentation of CD varies both according to the individual’s sex and level of callous-unemotional (CU) traits, but it remains unclear how genetic and environmental factors interact at the molecular level to produce these differences. Emerging evidence in males implicates methylation of genes associated with socio-affective processes. Here, we combined an epigenome-wide association study with structural neuroimaging in 51 females with CD and 59 typically developing (TD) females to examine DNA methylation in relation to CD, CU traits, and gray matter volume (GMV). We demonstrate an inverse pattern of correlation between CU traits and methylation of a chromosome 1 region in CD females (positive) as compared to TD females (negative). The identified region spans exon 1 of the SLC25A24 gene, central to energy metabolism due to its role in mitochondrial function. Increased SLC25A24 methylation was also related to lower GMV in multiple brain regions in the overall cohort. These included the superior frontal gyrus, dorsolateral prefrontal cortex, supramarginal gyrus, secondary visual cortex and ventral posterior cingulate cortex, which are regions that have previously been implicated in CD and CU traits. While our findings are preliminary and need to be replicated in larger samples, they provide novel evidence that CU traits in females are associated with methylation levels in a fundamentally different way in CD and TD individuals, which in turn may relate to observable variations in GMV across the brain.

Association Between Gray Matter Volume Variations and Energy Utilization in the Brain: Implications for Developmental Stuttering.

Purpose The biological mechanisms underlying developmental stuttering remain unclear. In a previous investigation, we showed that there is significant spatial correspondence between regional gray matter structural anomalies and the expression of genes linked to energy metabolism. In the current study, we sought to further examine the relationship between structural anomalies in the brain in children with persistent stuttering and brain regional energy metabolism. Method High-resolution structural MRI scans were acquired from 26 persistent stuttering and 44 typically developing children. Voxel-based morphometry was used to quantify the between-group gray matter volume (GMV) differences across the whole brain. Group differences in GMV were then compared with published values for the pattern of glucose metabolism measured via F18 fluorodeoxyglucose uptake in the brains of 29 healthy volunteers using positron emission tomography. Results A significant positive correlation between GMV differences and F18 fluorodeoxyglucose uptake was found in the left hemisphere (ρ = .36, p < .01), where speech-motor and language processing are typically localized. No such correlation was observed in the right hemisphere (ρ = .05, p = .70). Conclusions Corroborating our previous gene expression studies, the results of the current study suggest a potential connection between energy metabolism and stuttering. Brain regions with high energy utilization may be particularly vulnerable to anatomical changes associated with stuttering. Such changes may be further exacerbated when there are sharp increases in brain energy utilization, which coincides with the developmental period of rapid speech/language acquisition and the onset of stuttering during childhood. Supplemental Material https://doi.org/10.23641/asha.14110454.

Menstrual Cycle Variations in Gray Matter Volume, White Matter Volume and Functional Connectivity: Critical Impact on Parietal Lobe.

The role of gonadal hormones in neural plasticity remains unclear. This study aimed to examine the effects of naturally fluctuating hormone levels over the menstrual cycle in healthy females. Gray matter, functional connectivity (FC) and white matter changes over the cycle were assessed by using functional magnetic resonance imaging (fMRI), resting state fMRI, and structural MRIs, respectively, and associated with serum gonadal hormone levels. Moreover, electrocutaneous sensitivity was evaluated in 14 women in four phases of their menstrual cycle (menstrual, follicular, ovulatory, and luteal). Electrocutaneous sensitivity was greater during follicular compared to menstrual phase. Additionally, pain unpleasantness was lower in follicular phase than other phases while pain intensity ratings did not change over the cycle. Significant variations in cycle phase effects on gray matter volume were found in the left inferior parietal lobule (IPL) using voxel-based morphometry. Subsequent Freesurfer analysis revealed greater thickness of left IPL during the menstrual phase when compared to other phases. Also, white matter volume fluctuated across phases in left IPL. Blood estradiol was positively correlated with white matter volume both in left parietal cortex and whole cortex. Seed-driven FC between left IPL and right secondary visual cortex was enhanced during ovulatory phase. A seed placed in right IPL revealed enhanced FC between left and right IPL during the ovulatory phase. Additionally, we found that somatosensory cortical gray matter was thinner during follicular compared to menstrual phase. We discuss these results in the context of likely evolutionary pressures selecting for enhanced perceptual sensitivity across modalities specifically during ovulation.

The relationship between flow proneness in everyday life and variations in the volume of gray matter in the dopaminergic system: A cross-sectional study

Flow Proneness - FP (i.e., dispositional tendency to experience flow) is subjectively different across individuals. An earlier study demonstrated that FP is correlated with the availability of dopamine receptors in the dorsal striatum including the caudate and the putamen. However, it remains unclear whether FP is associated with gray matter volume variations in the brain. The neuro-anatomical basis of FP has been investigated for the first time in the present study. We conducted a cross-sectional study with a high number of healthy employed Japanese adults (n = 680). We measured FP in different domains of everyday life (work, household maintenance, and leisure time) using a Japanese translation of a Swedish flow proneness questionnaire. We investigated gray matter volume using optimized voxel-based morphometry. As hypothesized, we found a significant region in the dorsal striatum. Our results indicate that an increase in gray matter volume in the right caudate is associated with an increase in overall FP in everyday life. However, the resulting correlation was relatively small (0.13). We discuss the potential reasons underlying these findings. Our findings might have further implications for flow research and well-being.

Neuroanatomy of the vmPFC and dlPFC Predicts Individual Differences in Cognitive Regulation During Dietary Self-Control Across Regulation Strategies.

Making healthy food choices is challenging for many people. Individuals differ greatly in their ability to follow health goals in the face of temptation, but it is unclear what underlies such differences. Using voxel-based morphometry, we investigated in healthy humans (i.e., men and women) the links between structural variation in gray matter volume and individuals' level of success in shifting toward healthier food choices. We combined MRI and choice data into a joint dataset by pooling across three independent studies that used a task prompting participants to explicitly focus on the healthiness of food items before making their food choices. Within this dataset, we found that individual differences in gray matter volume in the ventromedial prefrontal cortex (vmPFC) and dorsolateral prefrontal cortex (dlPFC) predicted regulatory success. We extended and confirmed these initial findings by predicting regulatory success out of sample and across tasks in a second dataset requiring participants to apply a different regulation strategy that entailed distancing from cravings for unhealthy, appetitive foods. Our findings suggest that neuroanatomical markers in the vmPFC and dlPFC generalized to different forms of dietary regulation strategies across participant groups. They provide novel evidence that structural differences in neuroanatomy of two key regions for valuation and its control, the vmPFC and dlPFC, predict an individual's ability to exert control in dietary choices.SIGNIFICANCE STATEMENT Dieting involves regulating food choices to eat healthier foods and fewer unhealthy foods. People differ dramatically in their ability to achieve or maintain this regulation, but it is unclear why. Here, we show that individuals with more gray matter volume in the dorsolateral and ventromedial prefrontal cortex are better at exercising dietary self-control. This relationship was observed across four different studies examining two different forms of dietary self-regulation, suggesting that neuroanatomical differences in the ventromedial prefrontal cortex and dorsolateral prefrontal cortex may represent a general marker for self-control abilities. These results identify candidate neuroanatomical markers for dieting success and failure, and suggest potential targets for therapies aimed at preventing or treating obesity and related eating disorders.

Congenital olfactory impairment is linked to cortical changes in prefrontal and limbic brain regions.

The human sense of smell is closely associated with morphological differences of the fronto-limbic system, specifically the piriform cortex and medial orbitofrontal cortex (mOFC). Still it is unclear whether cortical volume in the core olfactory areas and connected brain regions are shaped differently in individuals who suffer from lifelong olfactory deprivation relative to healthy normosmic individuals. To address this question, we examined if regional variations in gray matter volume were associated with smell ability in seventeen individuals with isolated congenital olfactory impairment (COI) matched with sixteen normosmic controls. All subjects underwent whole-brain magnetic resonance imaging, and voxel-based morphometry was used to estimate regional variations in grey matter volume. The analyses showed that relative to controls, COI subjects had significantly larger grey matter volumes in left middle frontal gyrus and right superior frontal sulcus (SFS). COI subjects with severe olfactory impairment (anosmia) had reduced grey matter volume in the left mOFC and increased volume in right piriform cortex and SFS. Within the COI group olfactory ability, measured with the "Sniffin' Sticks" test, was positively associated with larger grey matter volume in right posterior cingulate and parahippocampal cortices whereas the opposite relationship was observed in controls. Across COI subjects and controls, better olfactory detectionthreshold was associated with smaller volume in right piriform cortex, while olfactory identification was negatively associated with right SFS volume. Our findings suggest that lifelong olfactory deprivation trigger changes in the cortical volume of prefrontal and limbic brain regions previously linked to olfactory memory.

The cerebellum's contribution to beat interval discrimination

From expert percussionists to individuals who cannot dance, there are widespread differences in people's abilities to perceive and synchronize with a musical beat. The aim of our study was to identify candidate brain regions that might be associated with these abilities.For this purpose, we used Voxel-Based-Morphometry to correlate inter-individual differences in performance on the Harvard Beat Assessment Tests (H-BAT) with local inter-individual variations in gray matter volumes across the entire brain space in 60 individuals.Analysis revealed significant co-variations between performances on two perceptual tasks of the Harvard Beat Assessment Tests associated with beat interval change discrimination (faster, slower) and gray matter volume variations in the cerebellum. Participant discrimination thresholds for the Beat Finding Interval Test (quarter note beat) were positively associated with gray matter volume variation in cerebellum lobule IX in the left hemisphere and crus I bilaterally. Discrimination thresholds for the Beat Interval Test (simple series of tones) revealed the tendency for a positive association with gray matter volume variations in crus I/II of the left cerebellum.Our results demonstrate the importance of the cerebellum in beat interval discrimination skills, as measured by two perceptual tasks of the Harvard Beat Assessment Tests. Current findings, in combination with evidence from patients with cerebellar degeneration and expert dancers, suggest that cerebellar gray matter and overall cerebellar integrity are important for temporal discrimination abilities.

Astrocytic water channel aquaporin-4 modulates brain plasticity in both mice and humans: a potential gliogenetic mechanism underlying language-associated learning.

The role of astrocytes in brain plasticity has not been extensively studied compared with that of neurons. Here we adopted integrative translational and reverse-translational approaches to explore the role of an astrocyte-specific major water channel in the brain, aquaporin-4 (AQP4), in brain plasticity and learning. We initially identified the most prevalent genetic variant of AQP4 (single nucleotide polymorphism of rs162008 with C or T variation, which has a minor allele frequency of 0.21) from a human database (n=60 706) and examined its functionality in modulating the expression level of AQP4 in an in vitro luciferase reporter assay. In the following experiments, AQP4 knock-down in mice not only impaired hippocampal volumetric plasticity after exposure to enriched environment but also caused loss of long-term potentiation after theta-burst stimulation. In humans, there was a cross-sectional association of rs162008 with gray matter (GM) volume variation in cortices, including the vicinity of the Perisylvian heteromodal language area (Sample 1, n=650). GM volume variation in these brain regions was positively associated with the semantic verbal fluency. In a prospective follow-up study (Sample 2, n=45), the effects of an intensive 5-week foreign language (English) learning experience on regional GM volume increase were modulated by this AQP4 variant, which was also associated with verbal learning capacity change. We then delineated in mice mechanisms that included AQP4-dependent transient astrocytic volume changes and astrocytic structural elaboration. We believe our study provides the first integrative evidence for a gliogenetic basis that involves AQP4, underlying language-associated brain plasticity.

Age-associated patterns in gray matter volume, cerebral perfusion and BOLD oscillations in children and adolescents.

Healthy brain development involves changes in brain structure and function that are believed to support cognitive maturation. However, understanding how structural changes such as grey matter thinning relate to functional changes is challenging. To gain insight into structure-function relationships in development, the present study took a data driven approach to define age-related patterns of variation in gray matter volume (GMV), cerebral blood flow (CBF) and blood-oxygen level dependent (BOLD) signal variation (fractional amplitude of low-frequency fluctuations; fALFF) in 59 healthy children aged 7-18 years, and examined relationships between modalities. Principal components analysis (PCA) was applied to each modality in parallel, and participant scores for the top components were assessed for age associations. We found that decompositions of CBF, GMV and fALFF all included components for which scores were significantly associated with age. The dominant patterns in GMV and CBF showed significant (GMV) or trend level (CBF) associations with age and a strong spatial overlap, driven by increased signal intensity in default mode network (DMN) regions. GMV, CBF and fALFF additionally showed components accounting for 3-5% of variability with significant age associations. However, these patterns were relatively spatially independent, with small-to-moderate overlap between modalities. Independence of age effects was further demonstrated by correlating individual subject maps between modalities: CBF was significantly less correlated with GMV and fALFF in older children relative to younger. These spatially independent effects of age suggest that the parallel decline observed in global GMV and CBF may not reflect spatially synchronized processes. Hum Brain Mapp 38:2398-2407, 2017. © 2017 Wiley Periodicals, Inc.

Brain gray matter alterations and associated demographic profiles in adults with autism spectrum disorder: A meta-analysis of voxel-based morphometry studies.

There is increasing evidence that children with autism spectrum disorder are accompanied by specific anatomical alterations. However, the anatomical abnormalities in adults with autism spectrum disorder are poorly understood. This study was aimed to identify the neuroanatomical substrates underlying the pathophysiology of adults with autism spectrum disorder. We also investigated the relationship between neuroanatomical alterations and clinical and demographic characteristics. A total of 13 datasets were enrolled, of which 12 studies compared whole-brain differences of 382 adult patients with autism and 393 healthy control subjects. We conducted a meta-analysis to quantitatively estimate regional gray matter volume abnormalities in individuals with autism using the effect-size signed differential mapping. The voxel-wise meta-analysis revealed that relative to controls, adults with autism spectrum disorder had significantly increased gray matter volume in the middle temporal gyrus, superior temporal gyrus, postcentral gyrus and parahippocampal gyrus, and reduced gray matter volume in the anterior cingulate cortex and cerebellum. Variations in gray matter volume were significantly associated with the mean age and mean total IQ score of the patients, as well as with the percentage of male patients with autism. These findings confirmed that the neuroanatomical alterations in the fronto-temporal cortices, limbic system and cerebellum in adult individuals with autism were different from the children and young adolescent's autism. The effects of demographic characteristics on the brain morphological changes allow us to further clarify the neurobiological mechanisms and developmental trajectory in adult population with autism spectrum disorder.

Cerebral gray matter volume variation in female-to-male transsexuals: a voxel-based morphometric study.

Several studies seem to support the hypothesis that brain anatomy is associated with transsexualism. However, these studies were still limited because few neuroanatomical findings have been obtained from female-to-male (FtM) transsexuals. This study compared the cerebral regional volumes of gray matter (GM) between FtM transsexuals and female controls using a voxel-based morphometry. Twelve FtM transsexuals who had undergone sex-reassignment surgery and 15 female controls participated in this study. Both groups were age matched and right-handed, with no history of neurological illness. Fifteen female controls were recruited to determine whether GM volumes in FtM transsexuals more closely resembled individuals who shared their biological sex. MRI data were processed using SPM 8 with the diffeomorphic anatomical registration through exponentiated Lie algebra (DARTEL). FtM transsexuals showed significantly larger volumes of the thalamus, hypothalamus, midbrain, gyrus rectus, head of caudate nucleus, precentral gyrus, and subcallosal area compared with the female controls. However, the female controls showed a significantly larger volume in the superior temporal gyrus including Heschl's gyrus and Rolandic operculum. These findings confirm that the volume difference in brain substructures in FtM transsexuals is likely to be associated with transsexualism and that transsexualism is probably associated with distinct cerebral structures, determining gender identity.

Common and distinct structural network abnormalities in major depressive disorder and borderline personality disorder

Major depressive disorder (MDD) and borderline personality disorder (BPD) show substantial overlap in both affective symptom expression and in regional brain volume reduction. To address the specificity of structural brain change for the respective diagnostic category, we investigated structural networks in MDD and BPD to identify shared and distinct patterns of abnormal brain volume associated with these phenotypically related disorders. Using magnetic resonance imaging at 3T, we studied 22 females with MDD, 17 females with BPD and without comorbid posttraumatic stress disorder, and 22 age-matched female healthy controls. We used “source-based morphometry” (SBM) to investigate naturally grouping patterns of gray matter volume variation (i.e. “structural networks”) and the magnitude of their expression between groups. SBM identified three distinct structural networks which showed a significant group effect (p<0.05, FDR-corrected). A bilateral frontostriatal network showed reduced volume in MDD compared to both controls and BPD patients. A medial temporal/medial frontal network was found to be significantly reduced in BPD compared to both controls and MDD patients. Decreased cingulate and lateral prefrontal volume was found in both MDD and BPD when compared to healthy individuals. In MDD significant relationships were found between depressive symptoms and a cingulate/lateral prefrontal structural pattern. In contrast, overall BPD symptoms and impulsivity scores were significantly associated with medial temporal/medial frontal network volume. The data suggest both distinct and common patterns of abnormal brain volume in MDD and BPD. Alterations of distinct structural networks differentially modulate clinical symptom expression in these disorders.

Association of regional gray matter volumes in the brain with disruptive behavior disorders in male and female children.

Because the disruptive behavior disorders are highly impairing conditions, it is important to determine if structural variations in brain are associated early in life with these problems among children.Structural MRI data were acquired from 111 9–11 year olds (58 girls and 53 boys), 43 who met diagnostic criteria for oppositional defiant disorder and/or conduct disorder and 68 healthy controls. Voxel-based morphometry was used to examine associations of behavioral measures with gray matter volumes in whole-brain analyses.Unlike previous studies, variation in gray matter volume was not found to be associated with a disruptive behavior disorder diagnosis in any brain region at p < .05 with FWE correction. Nonetheless, an inverse nonlinear association of the number of conduct disorder (CD) symptoms with gray matter volume along the left superior temporal sulcus was significant in the full sample (p < .05 with FWE correction), with a trend in the right hemisphere (p < 0.001 uncorrected). There also was a trend toward a stronger association of the number of CD symptoms with gray matter volume along the left superior temporal sulcus in girls than boys.The present findings did not replicate previous findings of reduced gray matter volumes in the anterior insula, amygdala, and frontal cortex in youth with CD, but are consistent with previous findings of reduced gray matter volumes in temporal regions, particularly in girls.

A gene−brain−cognition pathway for the effect of an Alzheimer׳s risk gene on working memory in young adults

Identifying pathways by which genetic Alzheimer׳s disease (AD) risk factors exert neurocognitive effects in young adults are essential for the effort to develop early interventions to forestall or prevent AD onset. Here, in a brain-imaging cohort of 59 young adults, we investigated effects of a variant within the clusterin (CLU) gene on working memory function and gray matter volume in cortical areas that support working memory. In addition, we investigated the extent to which effects of CLU genotype on working memory were independent of variation in the strongest AD risk factor gene apolipoprotein E (APOE). CLU is among the strongest genetic AD risk factors and, though it appears to share AD pathogenesis-related features with, APOE, it has been far less well studied. CLU genotype was associated with working memory performance in our study cohort. Notably, we found that variation in gray matter volume in a parietal region, previously implicated in maintenance of information for working memory, mediated the effect of CLU on working memory performance. APOE genotype did not affect working memory within our sample, and did not interact with CLU genotype. To our knowledge, this work represents the first evidence of a behavioral effect of CLU genotype in young people. In addition, this work identifies the first gene−brain−cognition mediation effect pathway for the transmission of the effect of an AD risk factor. Relative to conventional pairwise associations in cognitive neurogenetic research, gene−brain−cognition mediation modeling provides a more integrated understanding of how genetic effects transmit from gene to brain to cognitive function.

Different Brains Process Numbers Differently: Structural Bases of Individual Differences in Spatial and Nonspatial Number Representations

A dominant hypothesis on how the brain processes numerical size proposes a spatial representation of numbers as positions on a "mental number line." An alternative hypothesis considers numbers as elements of a generalized representation of sensorimotor-related magnitude, which is not obligatorily spatial. Here we show that individuals' relative use of spatial and nonspatial representations has a cerebral counterpart in the structural organization of the posterior parietal cortex. Interindividual variability in the linkage between numbers and spatial responses (faster left responses to small numbers and right responses to large numbers; spatial-numerical association of response codes effect) correlated with variations in gray matter volume around the right precuneus. Conversely, differences in the disposition to link numbers to force production (faster soft responses to small numbers and hard responses to large numbers) were related to gray matter volume in the left angular gyrus. This finding suggests that numerical cognition relies on multiple mental representations of analogue magnitude using different neural implementations that are linked to individual traits.

EPA-1018 - Source-based morphometry of gray matter volume in patients with schizophrenia who have persistent auditory verbal hallucinations

Abnormal brain structure of frontal and temporal brain regions has been suggested to occur in patients with schizophrenia who have frequent auditory verbal hallucinations (AVH). However, it is unknown whether this is specific to this patient subgroup. In this study tested the hypothesis that frontotemporal gray matter volume changes would characterize patients with persistent AVH (pAVH) in contrast to healthy controls and patients without AVH. Using structural magnetic resonance imaging at 3T, we studied 20 patients with schizophrenia and 14 matched healthy controls. Ten patients were classified as having chronic and treatment resistant AVH, whereas the remaining 10 patients either never had AVH in the past or were in full remission with regard to AVH (nAVH). Using a multivariate statistical technique for structural data, i.e. 'source-based morphometry' (SBM), we investigated naturally grouping patterns of gray matter volume variation among individuals, the magnitude of their expression between-groups and the relationship between gray matter volume and AVH-specific measures. SBM identified a lower expression of medial and inferior frontal as well as bilateral temporal gray matter volume between pAVH and nAVH. This pattern did not differ between nAVH patients and controls and was associated with 'physical' AVH characteristics (such as symptom duration, location, frequency and intensity) in the pAVH patient group. These results suggest that a pattern of lower gray matter volume in medial frontal and bilateral temporal cortical regions differentiates between patients with persistent AVH and non-hallucinating patients. Moreover, the data support a specific role of this neural pattern in AVH symptom expression.