Regional Gray Matter Volume Differences Research Articles

Use of cortical volume to predict response to temporary CSF drainage in patients with idiopathic normal pressure hydrocephalus.

Temporary drainage of CSF with lumbar puncture or lumbar drainage has a high predictive value for identifying patients with suspected idiopathic normal pressure hydrocephalus (iNPH) who may benefit from ventriculoperitoneal shunt insertion. However, it is unclear what differentiates responders from nonresponders. The authors hypothesized that nonresponders to temporary CSF drainage would have patterns of reduced regional gray matter volume (GMV) as compared with those of responders. The objective of the current investigation was to compare regional GMV between temporary CSF drainage responders and nonresponders. Machine learning using extracted GMV was then used to predict outcomes. This retrospective cohort study included 132 patients with iNPH who underwent temporary CSF drainage and structural MRI. Demographic and clinical variables were examined between groups. Voxel-based morphometry was used to calculate GMV across the brain. Group differences in regional GMV were assessed and correlated with change in results on the Montreal Cognitive Assessment (MoCA) and gait velocity. A support vector machine (SVM) model that used extracted GMV values and was validated with leave-one-out cross-validation was used to predict clinical outcome. There were 87 responders and 45 nonresponders. There were no group differences in terms of age, sex, baseline MoCA score, Evans index, presence of disproportionately enlarged subarachnoid space hydrocephalus, baseline total CSF volume, or baseline white matter T2-weighted hyperintensity volume (p > 0.05). Nonresponders demonstrated decreased GMV in the right supplementary motor area (SMA) and right posterior parietal cortex as compared with responders (p < 0.001, p < 0.05 with false discovery rate cluster correction). GMV in the posterior parietal cortex was associated with change in MoCA (r2 = 0.075, p < 0.05) and gait velocity (r2 = 0.076, p < 0.05). Response status was classified by the SVM with 75.8% accuracy. Decreased GMV in the SMA and posterior parietal cortex may help identify patients with iNPH who are unlikely to benefit from temporary CSF drainage. These patients may have limited capacity for recovery due to atrophy in these regions that are known to be important for motor and cognitive integration. This study represents an important step toward improving patient selection and predicting clinical outcomes in the treatment of iNPH.

Absence of associations with prefrontal cortex and cerebellum may link to early language and social deficits in preschool children with ASD.

Autism spectrum disorder (ASD) is a complex developmental disorder, characterized by language and social deficits that begin to appear in the first years of life. Research in preschool children with ASD has consistently reported increased global brain volume and abnormal cortical patterns, and the brain structure abnormalities have also been found to be clinically and behaviorally relevant. However, little is known regarding the associations between brain structure abnormalities and early language and social deficits in preschool children with ASD. In this study, we collected magnetic resonance imaging (MRI) data from a cohort of Chinese preschool children with and without ASD (24 ASD/20 non-ASD) aged 12-52 months, explored group differences in brain gray matter (GM) volume, and examined associations between regional GM volume and early language and social abilities in these two groups, separately. We observed significantly greater global GM volume in children with ASD as compared to those without ASD, but there were no regional GM volume differences between these two groups. For children without ASD, GM volume in bilateral prefrontal cortex and cerebellum was significantly correlated with language scores; GM volume in bilateral prefrontal cortex was significantly correlated with social scores. No significant correlations were found in children with ASD. Our data demonstrate correlations of regional GM volume with early language and social abilities in preschool children without ASD, and the absence of these associations appear to underlie language and social deficits in children with ASD. These findings provide novel evidence for the neuroanatomical basis associated with language and social abilities in preschool children with and without ASD, which promotes a better understanding of early deficits in language and social functions in ASD.

Correspondence Among Gray Matter Damage and Neurotransmitter Maps Is Clinically Relevant in Multiple Sclerosis (P10-3.004)

<h3>Objective:</h3> To investigate the associations among regional gray matter (GM) atrophy, neurotransmitter distributions and clinical manifestations in a large group of patients with multiple sclerosis (PwMS). <h3>Background:</h3> In multiple sclerosis (MS), clinically-relevant GM atrophy progresses in a non-random manner, possibly due to the preferential involvement of specific neurotransmitter networks, which has not been fully evaluated yet. <h3>Design/Methods:</h3> Brain 3.0 T MRI scans were acquired from 286 PwMS and 172 healthy controls (HC). Regional GM volume differences, cross-correlations between regional GM atrophy and nuclear imaging-derived neurotransmitter maps and their associations with disease duration, clinical disability, cognitive impairment, fatigue and depression were investigated using voxel-based morphometry and Juspace toolbox. <h3>Results:</h3> Compared to HC, PwMS showed a widespread cortico-subcortical GM atrophy being spatially correlated with serotonergic, dopaminergic, opioid, noradrenergic, cholinergic and glutamatergic maps (false discovery rate, [FDR]-p≤0.004). PwMS with a disease duration ≥5 vs &lt;5 years had a significant GM atrophy in several deep GM, cortical and cerebellar regions being spatially correlated with a higher distribution of serotoninergic and dopaminergic receptors (FDR-p≤0.03). Compared to mildly-disabled PwMS, those with Expanded Disability Status Scale (EDSS)≥3.0 or ≥4.0 had significant cortical, subcortical and cerebellar atrophy, which was associated with serotonergic and dopaminergic maps (FDR-p≤0.04). A significant spatial correspondence with opioid and cholinergic maps was also found for PwMS with EDSS≥4.0 vs &lt;4.0 (FDR-p≤0.04). Cognitively-impaired vs cognitively-preserved PwMS had a widespread GM atrophy being spatially correlated with serotonergic, dopaminergic, noradrenergic, cholinergic and glutamatergic maps (FDR-p≤0.04). PwMS with vs without fatigue had significant cortical, subcortical and cerebellar atrophy, which were associated with serotonergic, dopaminergic, opioid and glutamatergic maps (FDR-p≥0.07). No significant GM atrophy and associations with neurotransmitter maps were found according to depression. <h3>Conclusions:</h3> GM atrophy in regions belonging to specific neurotransmitter systems may contribute to explain part of MS clinical manifestations, including locomotor disability, cognitive impairment and fatigue. <b>Disclosure:</b> Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bristol Myers Squibb . Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi Genzyme. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck. Dr. Fiore has nothing to disclose. Dr. Tedone has nothing to disclose. Monica Margoni has received research support from MAGNIMS. Carmen Vizzino has nothing to disclose. Damiano Mistri has nothing to disclose. Dr. Gueye has nothing to disclose. Maria Assunta Rocca has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bayer, Biogen, Bristol Myers Squibb, Celgene, Genzyme, Merck Serono, Novartis, Roche, and Teva. The institution of Maria Assunta Rocca has received research support from Italian Ministry of Health, MS Society of Canada and Fondazione Italiana Sclerosi Multipla. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Bayer, Biogen Idec, Merck-Serono, Novartis, Roche, Sanofi Genzyme, Takeda, and Teva Pharmaceutical Industries. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Bayer, Biogen Idec, Merck-Serono, Novartis, Roche, Sanofi Genzyme, Takeda, and Teva Pharmaceutical Industries. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Springer Nature. The institution of Dr. Filippi has received research support from Biogen Idec, Merck-Serono, Novartis, Roche, Teva Pharmaceutical Industries, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, and ARiSLA (Fondazione Italiana di Ricerca per la SLA).

Correspondence among gray matter atrophy and atlas-based neurotransmitter maps is clinically relevant in multiple sclerosis.

In multiple sclerosis (MS), gray matter (GM) atrophy progresses in a non-random manner, possibly in regions with a high distribution of specific neurotransmitters involved in several relevant central nervous system functions. We investigated the associations among regional GM atrophy, atlas-based neurotransmitter distributions and clinical manifestations in a large MS patients' group. Brain 3 T MRI scans, neurological examinations and neuropsychological evaluations were obtained from 286 MS patients and 172 healthy controls (HC). Spatial correlations among regional GM volume differences and atlas-based nuclear imaging-derived neurotransmitter maps, and their associations with MS clinical features were investigated using voxel-based morphometry and JuSpace toolbox. Compared to HC, MS patients showed widespread GM atrophy being spatially correlated with the majority of neurotransmitter maps (false discovery rate [FDR]-p ≤ 0.004). Patients with a disease duration ≥ 5 vs < 5 years had significant cortical, subcortical and cerebellar atrophy, being spatially correlated with a higher distribution of serotoninergic and dopaminergic receptors (FDR-p ≤ 0.03). Compared to mildly-disabled patients, those with Expanded Disability Status Scale ≥ 3.0 or ≥ 4.0 had significant cortical, subcortical and cerebellar atrophy being associated with serotonergic, dopaminergic, opioid and cholinergic maps (FDR-p ≤ 0.04). Cognitivelyimpaired vs cognitivelypreserved patients had widespread GM atrophy being spatially associated with serotonergic, dopaminergic, noradrenergic, cholinergic and glutamatergic maps (FDR-p ≤ 0.04). Fatigued vs non-fatigued MS patients had significant cortical, subcortical and cerebellar atrophy, not associated with neurotransmitter maps. No significant association between GM atrophy and neurotransmitter maps was found for depression. Regional GM atrophy with specific neurotransmitter systems may explain part of MS clinical manifestations, including locomotor disability, cognitive impairment and fatigue.

Cognitive impairment in mild traumatic brain injury: a diffusion kurtosis imaging and volumetric study.

A significant number of patients with mild traumatic brain injury (mTBI) would experience cognitive deficit. To investigate the brain structural changes in sub-acute mTBI by diffusion kurtosis imaging (DKI) and volumetric analysis, and to assess the relationship between brain structural changes and cognitive functions. A total of 23 patients with sub-acute mTBI and 24 control participants were recruited. All the participants underwent examinations of neuropsychological tests, DKI, and magnetic resonance imaging (MRI)-based morphological scans. Images were investigated using whole brain-based analysis and further regions of interest-based analysis for subcortical nuclei. The neuropsychological tests were compared between the mTBI and the control group. Correlation analysis was performed to examine the relationship between gray matter (GM) volume, DKI parameters, and cognitive functions. Compared with control participants, mTBI patients performed worse in the domains of verbal memory, attention and executive function (P < 0.05). No regional GM volume differences were observed between the mTBI and control groups (P > 0.05). Using DKI, patients with mTBI showed lower mean kurtosis (MK) in widespread white matter (WM) regions and several subcortical nuclei (P < 0.05), and higher mean diffusivity (MD) in the right pallidum (P < 0.05). Lower MK value of multiple WM regions and several subcortical nuclei correlated with cognitive impairment (P < 0.05). DKI was sensitive in detecting brain microstructural changes in patients with sub-acute mTBI showing lower MK value in widespread WM regions and several subcortical nuclei, which were statistically associated with cognitive deficits.

Regional brain volume predicts response to methylphenidate treatment in individuals with ADHD

BackgroundDespite the effectiveness of methylphenidate for treating ADHD, up to 30% of individuals with ADHD show poor responses to methylphenidate. Neuroimaging biomarkers to predict medication responses remain elusive. This study characterized neuroanatomical features that differentiated between clinically good and poor methylphenidate responders with ADHD.MethodsUsing a naturalistic observation design selected from a larger cohort, we included 79 drug-naive individuals (aged 6–42 years) with ADHD without major psychiatric comorbidity, who had acceptable baseline structural MRI data quality. Based on a retrospective chart review, we defined responders by individuals’ responses to at least one-month treatment with methylphenidate. A nonparametric mass-univariate voxel-based morphometric analysis was used to compare regional gray matter volume differences between good and poor responders. A multivariate pattern recognition based on the support vector machine was further implemented to identify neuroanatomical indicators to predict an individual’s response.Results63 and 16 individuals were classified in the good and poor responder group, respectively. Using the small-volume correction procedure based on the hypothesis-driven striatal and default-mode network masks, poor responders had smaller regional volumes of the left putamen as well as larger precuneus volumes compared to good responders at baseline. The machine learning approach identified that volumetric information among these two regions alongside the left frontoparietal regions, occipital lobes, and posterior/inferior cerebellum could predict clinical responses to methylphenidate in individuals with ADHD.ConclusionOur results suggest regional striatal and precuneus gray matter volumes play a critical role in mediating treatment responses in individuals with ADHD.

Differential patterns of gray matter volumes and associated gene expression profiles in cognitively-defined Alzheimer’s disease subgroups

The clinical presentation of Alzheimer’s disease (AD) varies widely across individuals but the neurobiological mechanisms underlying this heterogeneity are largely unknown. Here, we compared regional gray matter (GM) volumes and associated gene expression profiles between cognitively-defined subgroups of amyloid-β positive individuals clinically diagnosed with AD dementia (age: 66 ± 7, 47% male, MMSE: 21 ± 5). All participants underwent neuropsychological assessment with tests covering memory, executive-functioning, language and visuospatial-functioning domains. Subgroup classification was achieved using a psychometric framework that assesses which cognitive domain shows substantial relative impairment compared to the intra-individual average across domains, which yielded the following subgroups in our sample; AD-Memory (n = 41), AD-Executive (n = 117), AD-Language (n = 33), AD-Visuospatial (n = 171). We performed voxel-wise contrasts of GM volumes derived from 3Tesla structural MRI between subgroups and controls (n = 127, age 58 ± 9, 42% male, MMSE 29 ± 1), and observed that differences in regional GM volumes compared to controls closely matched the respective cognitive profiles. Specifically, we detected lower medial temporal lobe GM volumes in AD-Memory, lower fronto-parietal GM volumes in AD-Executive, asymmetric GM volumes in the temporal lobe (left < right) in AD-Language, and lower GM volumes in posterior areas in AD-Visuospatial. In order to examine possible biological drivers of these differences in regional GM volumes, we correlated subgroup-specific regional GM volumes to brain-wide gene expression profiles based on a stereotactic characterization of the transcriptional architecture of the human brain as provided by the Allen human brain atlas. Gene-set enrichment analyses revealed that variations in regional expression of genes involved in processes like mitochondrial respiration and metabolism of proteins were associated with patterns of regional GM volume across multiple subgroups. Other gene expression vs GM volume-associations were only detected in particular subgroups, e.g., genes involved in the cell cycle for AD-Memory, specific sets of genes related to protein metabolism in AD-Language, and genes associated with modification of gene expression in AD-Visuospatial. We conclude that cognitively-defined AD subgroups show neurobiological differences, and distinct biological pathways may be involved in the emergence of these differences.

Larger whole brain grey matter associated with long-term Sahaja Yoga Meditation: A detailed area by area comparison.

Our previous study showed that long-term practitioners of Sahaja Yoga Meditation (SYM) had around 7% larger grey matter volume (GMV) in the whole brain compared with healthy controls; however, when testing individual regions, only 5 small brain areas were statistically different between groups. Under the hypothesis that those results were statistically conservative, with the same dataset, we investigated in more detail the regional differences in GMV associated with the practice of SYM, with a different statistical approach. Twenty-three experienced practitioners of SYM and 23 healthy non-meditators matched on age, sex and education level, were scanned using structural magnetic resonance imaging (MRI). Their GMV were extracted and compared using Voxel-Based Morphometry (VBM). Using a novel ad-hoc general linear model, statistical comparisons were made to observe if the GMV differences between meditators and controls were statistically significant. In the 16 lobe area subdivisions, GMV was statistically significantly different in 4 out of 16 areas: in right hemispheric temporal and frontal lobes, left frontal lobe and brainstem. In the 116 AAL area subdivisions, GMV difference was statistically significant in 11 areas. The GMV differences were statistically more significant in right hemispheric brain areas. The study shows that long-term practice of SYM is associated with larger GMV overall, and with significant differences mainly in temporal and frontal areas of the right hemisphere and the brainstem. These neuroplastic changes may reflect emotional and attentional control mechanisms developed with SYM. On the other hand, our statistical ad-hoc method shows that there were more brain areas with statistical significance compared to the traditional methodology which we think is susceptible to conservative Type II errors.

Hippocampal subfield morphology in monozygotic twins discordant for affective disorders.

Unipolar and bipolar disorders aggregate in families and have been associated with a reduced gray-matter volume in hippocampal and prefrontal cortex. Here we used structural MRI to clarify whether abnormalities in hippocampal subfield and prefrontal cortical morphology are associated with familial vulnerability (i.e., changes present both in patients and unaffected relatives compared to healthy individuals), resilience (i.e., changes differentiating unaffected relatives and patients), or sequalae of illness in a sample of monozygotic twins. We investigated regional differences in gray-matter volume extracted using FreeSurfer 6.0 between remitted affected twins (AT) with either unipolar or bipolar disorder (n = 67), unaffected discordant co-twins (UT, n = 39), and low-risk twins (LT, n = 31) with no personal or first-degree family history of affective disorders. The UT showed greater bilateral hippocampal volumes compared to AT. Between group differences in left hippocampal volume were driven by greater cornu ammonis 1-3 and 4, subiculum and subfield of dentate gyrus. For the right hippocampus, differences were driven by greater hippocampal tail and subiculum. There was a trend for UT having a larger left hippocampus than LT, but no significant differences in hippocampal volumes between AT and LT. Outside the hippocampus, AT showed a smaller volume of left dorsomedial prefrontal cortex compared to LT. Our results suggest that larger volume of specific hippocampal subfields may be associated with resilience in healthy relatives of patients with an affective illness. Moreover, a smaller volume of left dorsomedial prefrontal cortex may reflect a sequalae of illness.

Association between tooth loss and gray matter volume in cognitive impairment.

Previous studies have reported an association between tooth loss and gray matter volume (GMV) in healthy adults. The study aims to elucidate the link between tooth loss, brain volume differences, and cognitive impairment by investigating the total and regional differences in GMV associated with tooth loss in older people with and without cognitive impairment. Forty older participants with mild cognitive impairment or Alzheimer's disease [the cognitive impairment (CI) group] and 30 age- and sex-matched healthy participants [the control (CON) group] received T1-weighted magnetic resonance imaging scans and assessments of oral functions, including masticatory performance (MP) and the number of missing teeth (NMT). Voxel-based morphometry was used to assess the total and regional GMV, including that of the medial temporal lobe and motor-related areas. (A) When the total intracranial volume and age were controlled for, an increased MP was associated with a larger GMV in the premotor cortex in the CON group. (B) In the CI group, an increased NMT was significantly correlated with smaller regional GMV of the bilateral primary motor cortex and the premotor cortex. (C) In the CI group, but not the CON group, an increased NMT was associated with both smaller total GMV and regional GMV of the left medial temporal lobe, including the left hippocampus and parahippocampus. Tooth loss may be preferentially related to the structural differences in the medial temporal lobe in cognitively impaired older people. Further research is required to understand the mechanisms of the relationships.

Associations between Brain Structural Damage and Core Muscle Loss in Patients with Parkinson's Disease.

Background: Parkinson’s disease (PD) is a common neurodegenerative disease associated with progressive gray matter atrophy. In addition to motor function disorder, frailty and decreased muscle mass potentially contribute to increased morbidity risk. Objective: This study aimed to investigate the associations between lean muscle loss and gray matter volume (GMV) in PD patients. Methods: Thirty patients with PD and fifteen healthy controls underwent brain and bilateral thigh MRIs. The IDEAL sequence was employed, measuring the regions of interest (ROI) of fat percentage at the 50% point of femur length. Voxel-base morphometry (VBM) was used to assess regional gray matter volume differences between groups. Further correlation analysis was performed to evaluate the changes between gray matter volume and fatty percentage of the bilateral thigh after adjusting for age and gender. Multiple linear regression analysis was applied to evaluate the risk factor of core muscle loss in PD patients. Results: Compared with controls, patients with PD had significantly higher thigh fat percentage and smaller gray matter volume of several brain locations of the default mode network (DMN), specifically the left superior temporal gyrus, right uncus, and left inferior temporal gyrus, revealing association with higher thigh fat percentage. Further multiple linear regression analysis indicated that higher thigh fat percentage is associated with gender (female), increased disease duration, and smaller gray matter volume of the left superior temporal gyrus and right uncus in PD patients. Conclusions: Patients with PD experience core muscle loss in the thigh, associated with default mode network (DMN) degeneration, longer disease duration, and female gender. Identification of risk factors associated with lean muscle mass loss may assist in early prevention of comorbidities such as sarcopenia.

Associations of Regional Brain Structural Differences With Aging, Modifiable Risk Factors for Dementia, and Cognitive Performance

Identifying brain regions associated with risk factors for dementia could guide mechanistic understanding of risk factors associated with Alzheimer disease (AD). To characterize volume changes in brain regions associated with aging and modifiable risk factors for dementia (MRFD) and to test whether volume differences in these regions are associated with cognitive performance. This cross-sectional study used data from UK Biobank participants who underwent T1-weighted structural brain imaging from August 5, 2014, to October 14, 2016. A voxelwise linear model was applied to test for regional gray matter volume differences associated with aging and MRFD (ie, hypertension, diabetes, obesity, and frequent alcohol use). The potential clinical relevance of these associations was explored by comparing their neuroanatomical distributions with the regional brain atrophy found with AD. Mediation models for risk factors, brain volume differences, and cognitive measures were tested. The primary hypothesis was that common, overlapping regions would be found. Primary analysis was conducted on April 1, 2018. Gray matter regions that showed relative atrophy associated with AD, aging, and greater numbers of MRFD. Among 8312 participants (mean [SD] age, 62.4 [7.4] years; 3959 [47.1%] men), aging and 4 major MRFD (ie, hypertension, diabetes, obesity, and frequent alcohol use) had independent negative associations with specific gray matter volumes. These regions overlapped neuroanatomically with those showing lower volumes in participants with AD, including the posterior cingulate cortex, the thalamus, the hippocampus, and the orbitofrontal cortex. Associations between these MRFD and spatial memory were mediated by differences in posterior cingulate cortex volume (β = 0.0014; SE = 0.0006; P = .02). This cross-sectional study identified differences in localized brain gray matter volume associated with aging and MRFD, suggesting regional vulnerabilities. These differences appeared relevant to cognitive performance even among people considered cognitively healthy.

Altered brain structural and cognitive impairment in end-stage renal disease patients with secondary hyperparathyroidism.

Cognitive impairment has received attention as an important problem in patients with end-stage renal disease, although end-stage renal disease patients with secondary hyperparathyroidism have not been studied. To assess the pattern of brain volume changes in end-stage renal disease patients with secondary hyperparathyroidism by using voxel-based morphometry and correlating these measures with clinical markers and the Montreal Cognitive Assessment scores. Fifty end-stage renal disease patients with no anatomical abnormalities in conventional MRI (25 patients with secondary hyperparathyroidism, 14 men, mean age 42.20 ± 7.53 years; 25 patients without secondary hyperparathyroidism, 15 men, mean age 41.96 ± 6.17 years) were selected in this study. All patients underwent laboratory tests, neuropsychological tests, and MRI. Voxel-based morphometry analysis was performed to detect regional gray matter volume differences between the two groups. The relationships between abnormal gray matter volume and clinical markers and Montreal Cognitive Assessment scores were investigated. Voxel-based morphometry revealed increased gray matter volume in end-stage renal disease patients with secondary hyperparathyroidism in the bilateral caudate and bilateral thalamus compared with non- secondary hyperparathyroidism end-stage renal disease patients (P < 0.05, FWE corrected). Regarding the laboratory and neuropsychological tests, we found significant correlations between volume in these brain regions and intact parathyroid hormone levels and negative correlations with the Montreal Cognitive Assessment scores. There were no significant associations between brain volume changes and other clinical data (disease duration, urea, creatinine, and uric acid levels). Our results showed significantly increased gray matter volume in end-stage renal disease patients with secondary hyperparathyroidism, which was associated with intact parathyroid hormone levels and cognitive impairment. Serum intact parathyroid hormone levels may be a risk factor for cognitive impairment in end-stage renal disease patients with secondary hyperparathyroidism.

Altered brain morphology in chronic pancreatitis patients and its association with pain and other disease characteristics.

Abnormal pain processing in the central nervous system is a hallmark of chronic pancreatitis (CP). We characterized brain structure in CP patients and identified disease characteristics that impact the brain structure in CP patients. Thirty-three CP patients and 23 matched healthy controls underwent brain MRI. Total and regional gray matter volume (GMV) and cortical thickness analyses were carried out. Multivariate linear regression models were used to determine the independent predictors of total GMV. CP patients had 31.9 ± 9.3 ml (mean ± SE) (5.1%) reduced total GMV compared with the healthy controls (587.1 ± 5.8 vs. 619.0 ± 7.0 cm, P < 0.001). Alcoholic etiology was associated independently with a decreased total GMV (P < 0.001), whereas no association was observed for pain or other disease characteristics (all P > 0.05). Similarly, regional GMV loss and cortical thinning were observed for several cortical areas in patients with alcoholic etiology compared with their nonalcoholic counterparts (P < 0.05). These regional differences were particularly evident for pain-related cortical areas; however, no significant differences in regional GMV or cortical thickness were observed between patients with and without pain (all P > 0.05). Patients with CP have GMV loss that is associated with alcoholic disease etiology. No associations were detected between pain and GMV loss, likely because the potential effect of long-lasting pain on brain structure is masked by the effects of previous alcohol use. The findings imply that alcoholic etiology is the most prominent contributing factor for structural brain alterations in CP patients.

A neural signature of metabolic syndrome.

That metabolic syndrome (MetS) is associated with age-related cognitive decline is well established. The neurobiological changes underlying these cognitive deficits, however, are not well understood. The goal of this study was to determine whether MetS is associated with regional differences in gray-matter volume (GMV) using a cross-sectional, between-group contrast design in a large, ethnically homogenous sample. T1-weighted MRIs were sampled from the genetics of brain structure (GOBS) data archive for 208 Mexican-American participants: 104 participants met or exceeded standard criteria for MetS and 104 participants were age- and sex-matched metabolically healthy controls. Participants ranged in age from 18 to 74 years (37.3 ± 13.2 years, 56.7% female). Images were analyzed in a whole-brain, voxel-wise manner using voxel-based morphometry (VBM). Three contrast analyses were performed, a whole sample analysis of all 208 participants, and two post hoc half-sample analyses split by age along the median (35.5 years). Significant associations between MetS and decreased GMV were observed in multiple, spatially discrete brain regions including the posterior cerebellum, brainstem, orbitofrontal cortex, bilateral caudate nuclei, right parahippocampus, right amygdala, right insula, lingual gyrus, and right superior temporal gyrus. Age, as shown in the post hoc analyses, was demonstrated to be a significant covariate. A further functional interpretation of the structures exhibiting lower GMV in MetS reflected a significant involvement in reward perception, emotional valence, and reasoning. Additional studies are needed to characterize the influence of MetS's individual clinical components on brain structure and to explore the bidirectional association between GMV and MetS.

Nerve Growth Factor Serum Levels Are Associated With Regional Gray Matter Volume Differences in Schizophrenia Patients.

Numerous neuroimaging studies have revealed structural brain abnormalities in schizophrenia patients. There is emerging evidence that dysfunctional nerve growth factor (NGF) signaling may contribute to structural brain alterations found in these patients. In this pilot study, we investigated whether there was a correlation between NGF serum levels and gray matter volume (GMV) in schizophrenia patients. Further, we investigated whether there was an overlap between the correlative findings and cross-sectional GMV differences between schizophrenia patients (n = 18) and healthy controls (n = 19). Serum NGF was significantly correlated to GMV in the left prefrontal lobe, the left midcingulate cortex, and the brainstem in schizophrenia patients. However, we did not find any correlations of NGF serum levels with GMV in healthy controls. Schizophrenia patients showed smaller GMV than healthy controls in brain regions located in the bilateral limbic system, bilateral parietal lobe, bilateral insula, bilateral primary auditory cortex, left frontal lobe, and bilateral occipital regions. In a conjunction analysis, GMV in the left midcingulate cortex (MCC) appears negatively correlated to NGF serum levels in the group of schizophrenia patients and also to be reduced compared to healthy controls. These results suggest an increased vulnerability of schizophrenia patients to changes in NGF levels compared to healthy controls and support a role for NGF signaling in the pathophysiology of schizophrenia. As our pilot study is exploratory in nature, further studies enrolling larger sample sizes will be needed to further corroborate our findings and to investigate the influence of additional covariates.

Nonlinear neuroplasticity corresponding to sports experience: A voxel-based morphometry and resting-state functional connectivity study.

We aimed to investigate the structural neuroplasticity associated with different levels of sports experience and its effect on the corresponding resting-state functional circuitry. We recruited 18 skilled baseball batters (SB), 19 intermediate baseball batters (IB), and 17 healthy controls (HC), and used magnetic resonance imaging methods to compare their regional gray-matter volume (GMV) and seed-based resting-state functional connectivity (rsFC). Our results revealed that a quadratic function could better depict intergroup differences in regional GMV than a linear function. In particular, the IB showed lower or higher regional GMV than the other two groups. The difference in GMV in the supplementary motor area and areas belonging to the ventral stream, including the middle temporal gyrus and middle temporal pole, might be possibly related to baseball-specific motor and perceptual experience, such as inhibitory action control and pitch identification. On the other hand, the stronger rsFC seeded from the right middle temporal pole to the default mode network, particularly in the precuneus, in the SB and IB relative to that in the HC might be possibly associated with the theory of mind, such as deciding whether to swing or not against the pitcher by detecting the spatial information of pitches. In conclusion, our three-group design enabled the capture of the unique and transient changes that occur during the intermediate phase of expertise development. Our findings indicated that structural and functional brain changes do not necessarily linearly increase as a function of experience as previously suggested by the literature.

A Voxel-Wise Meta-Analysis of Gray Matter Abnormalities in Essential Tremor.

Objective: To identify the consistent gray matter (GM) volume changes from the whole brain voxel-based morphometry (VBM) studies on essential tremor (ET).Methods: The whole brain VBM studies comparing ET patients and healthy controls (HCs) were systematically searched in the PubMed, Embase and Web of Science from January 2000 to December 2017. Coordinates with significant differences in regional GM volume between ET patients and HCs were extracted from included studies and the meta-analysis was performed using effect size-based signed differential mapping (ES-SDM).Results: A total of 10 studies with 241 ET patients and 213 HCs were included in the meta-analysis. The consistent GM volume reduction was detected in the left precuneus extending to the left posterior cingulate gyrus. The subgroup meta-analysis which included studies performed on a 3.0 T scanner revealed significant GM volume increases in the bilateral frontal lobes, bilateral temporal lobes, left insula, left striatum and left pons, but obvious publication biases of these findings were detected through funnel plots and Egger's tests.Conclusions: The consistent result of our meta-analysis showed a structural damage in the left precuneus extending to the left posterior cingulate gyrus, which possibly played a role in the cognitive dysfunction and depression in ET patients. It might enhance our understanding of the pathophysiological mechanisms underlying ET.

Brain gray matter volume differences in obese youth with type 2 diabetes: a pilot study.

Adults with type 2 diabetes (T2D) have significantly lower gray matter volume (GMV) compared to healthy peers. Whether GMV differences exist in youth with T2D remains unclear. Thus, we compared global and regional GMV between obese youth with T2D with age, race and sex similar healthy controls. In a cross-sectional study, 20 obese youth with T2D underwent T1-weighted brain magnetic resonance imaging (MRI). Comparisons were made to 20 age, race and sex similar controls. Differences in global and regional GMV between groups were identified using voxel-based morphometry (VBM). Youth with T2D had a significantly lower global GMV-to-intracranial volume ratio (0.51±0.02 in T2D vs. 0.53±0.02 in controls, p=0.02, Cohen's d=0.85). There were 14 regions where GMV was significantly lower in the T2D group, and nine of these were found in either the temporal or occipital lobes. There were six regions with increased GMV in T2D. All regional differences were significant at p<0.05 after adjusting for multiple comparisons. Results from this pilot study show obese youth with T2D have significantly lower global GMV and regional GMV differences, when compared to their age, race and sex similar peers. Future work is needed to determine whether these brain findings are a direct result of adolescent-onset T2D.

Brain Structural Differences between Normal and Obese Adults and their Links with Lack of Perseverance, Negative Urgency, and Sensation Seeking

In order to examine the difference in brain structure between obese and normal weight individuals, and to explore the relationship between the neuroanatomical changes and impulsivity traits, this study used a voxel-based morphometry method to examine gray matter (GM) volume alterations related to impulsive personality traits in obese individuals relative to normal weight. Eighty adults that completed the UPPS-P Impulsive Behavior Scale were analyzed. Possible GM volume alterations were first analyzed at the whole brain level, and then the relationship between regional GM volume differences and UPPS-P scores were examined in selected regions of interest. Reduced GM volumes were found in the frontal and limbic regions in the obese group compared to normal weight individuals. In the normal weight group, lack of perseverance was negatively correlated with GM volume in the anterior cingulate cortex, and negative urgency was negatively correlated with GM volume in the insula. In the obese group, sensation seeking was negatively correlated with GM volume in the left amygdala and right pallidum. These findings might improve our understanding of the relationship between lack of perseverance, negative urgency, and sensation seeking and body weight fluctuations.