scholarly journals Linking lysosomal enzyme targeting genes and energy metabolism with altered gray matter volume in children with persistent stuttering

2019 ◽  
Author(s):  
Ho Ming Chow ◽  
Emily O. Garnett ◽  
Hua Li ◽  
Andrew Etchell ◽  
Jorge Sepulcre ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gray Matter ◽  
Structural Changes ◽  
Neurodevelopmental Disorder ◽  
Gray Matter Volume ◽  
Expression Patterns ◽  
High Energy ◽  
Energy Utilization ◽  
Matter Volume ◽  
Heritable Disorder

AbstractDevelopmental stuttering is a childhood onset neurodevelopmental disorder with an unclear etiology. Subtle changes in brain structure and function are present in both children and adults who stutter. It is a highly heritable disorder, and up to 12-20% of stuttering cases may carry a mutation in one of four genes involved in mannose-6-phosphate mediated protein intracellular trafficking. To better understand the relationship between genetic factors and brain structural changes, we used gene expression data from the Allen Institute for Brain Science (AIBS) and voxel-based morphometry (VBM) to investigate the spatial correspondence between gene expression patterns and differences in gray matter volume (GMV) between children with persistent stuttering (n=26, 87 scans) and their fluent peers (n=44, 139 scans). We found that expression patterns of two stuttering-related genes (GNPTG and NAGPA) in the brain exhibit a strong positive spatial correlation with the magnitude of GMV differences between groups. Further gene set enrichment analyses revealed that genes whose expression was highly correlated with the GMV differences were enriched for glycolysis and oxidative metabolism in mitochondria. Although the results are correlational and cannot inform us about underlying casual mechanisms, our results suggest a possibility that regions with high expression level of genes associated with stuttering may be particularly vulnerable to the effect of alterations in these genes. This effect may be further exacerbated by the relatively high energy utilization in those brain during the period of a sharp increase in brain energy utilization, which coincides with a period of rapid language development and the onset of stuttering during childhood.

scholarly journals Linking Lysosomal Enzyme Targeting Genes and Energy Metabolism with Altered Gray Matter Volume in Children with Persistent Stuttering

2020 ◽  
Vol 1 (3) ◽  
pp. 365-380
Author(s):  
Ho Ming Chow ◽  
Emily O. Garnett ◽  
Hua Li ◽  
Andrew Etchell ◽  
Jorge Sepulcre ◽  
...  
Keyword(s):  
Gene Expression ◽  
Energy Metabolism ◽  
Gray Matter ◽  
Lysosomal Enzyme ◽  
Neurodevelopmental Disorder ◽  
Gray Matter Volume ◽  
Expression Patterns ◽  
Spatial Relationship ◽  
Matter Volume ◽  
Enzyme Targeting

Developmental stuttering is a childhood onset neurodevelopmental disorder with an unclear etiology. Subtle changes in brain structure and function are present in both children and adults who stutter. It is a highly heritable disorder, and 12–20% of stuttering cases may carry a mutation in one of four genes involved in intracellular trafficking. To better understand the relationship between genetics and neuroanatomical changes, we used gene expression data from the Allen Institute for Brain Science and voxel-based morphometry to investigate the spatial correspondence between gene expression patterns and differences in gray matter volume between children with persistent stuttering ( n = 26, and 87 scans) and their fluent peers ( n = 44, and 139 scans). We found that the expression patterns of two stuttering-related genes ( GNPTG and NAGPA) from the Allen Institute data exhibited a strong positive spatial correlation with the magnitude of between-group gray matter volume differences. Additional gene set enrichment analyses revealed that genes whose expression was highly correlated with the gray matter volume differences were enriched for glycolysis and oxidative metabolism in mitochondria. Because our current study did not examine the participants’ genomes, these results cannot establish the direct association between genetic mutations and gray matter volume differences in stuttering. However, our results support further study of the involvement of lysosomal enzyme targeting genes, as well as energy metabolism in stuttering. Future studies assessing variations of these genes in the participants’ genomes may lead to increased understanding of the biological mechanisms of the observed spatial relationship between gene expression and gray matter volume.

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

2021 ◽  
pp. 1-8
Author(s):  
Nathaniel Boley ◽  
Sanath Patil ◽  
Emily O. Garnett ◽  
Hua Li ◽  
Diane C. Chugani ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Gray Matter ◽  
Right Hemisphere ◽  
Gray Matter Volume ◽  
High Energy ◽  
Energy Utilization ◽  
Matter Volume ◽  
Developmental Stuttering ◽  
The Brain ◽  
Structural Anomalies

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 F 18 fluorodeoxyglucose uptake in the brains of 29 healthy volunteers using positron emission tomography. Results A significant positive correlation between GMV differences and F 18 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

scholarly journals Moderating Effect of Insulin Resistance on the Relationship between Gray Matter Volumes and Cognitive Function

2018 ◽  
Vol 7 (11) ◽  
pp. 413 ◽  
Author(s):  
Jiyeon Lee ◽  
Jihyeon Kim ◽  
Seong Shin ◽  
Soowon Park ◽  
Dong Yoon ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Insulin Resistance ◽  
Alzheimer's Disease ◽  
Cognitive Function ◽  
Cognitive Decline ◽  
Gray Matter ◽  
Structural Changes ◽  
Gray Matter Volume ◽  
Volume Loss ◽  
Matter Volume

Background: It is controversial whether exposure to insulin resistance accelerates cognitive deterioration. The present study aimed to investigate the association between insulin resistance and gray matter volume loss to predict the cognitive decline. Methods: We recruited 160 participants (78 with Alzheimer’s disease and 82 without Alzheimer’s disease). Insulin resistance, regional gray matter volume, and cognitive function were assessed. A hierarchical moderated multiple regression (MMR) model was used to determine any associations among insulin resistance, structural changes in the brain, and cognitive decline. Results: The volumes of 7 regions in the gray matter were negatively related to insulin resistance in Alzheimer’s disease (p =0.032). Hierarchical MMR analysis indicated that insulin resistance did not directly affect the cognitive decline but moderated the cognitive decline through the decrease in gray matter volume in the key brain regions, i.e., inferior orbitofrontal gyrus (left), middle cingulate gyrus (right), hippocampus (right), and precuneus (right) (p < 0.05 in each case). Conclusion: Insulin resistance appears to exacerbate the cognitive decline associated with several gray matter volume loss.

scholarly journals The Association between Gray Matter Volume and Reading Proficiency: A Longitudinal Study of Beginning Readers

2015 ◽  
Vol 27 (2) ◽  
pp. 308-318 ◽  
Author(s):  
Janosch Linkersdörfer ◽  
Alina Jurcoane ◽  
Sven Lindberg ◽  
Jochen Kaiser ◽  
Marcus Hasselhorn ◽  
...  
Keyword(s):  
Reading Instruction ◽  
Gray Matter ◽  
Structural Changes ◽  
Gray Matter Volume ◽  
Negative Relationship ◽  
Reading Proficiency ◽  
Superior Temporal Gyrus ◽  
Measurement Time ◽  
Cortical Volume ◽  
Matter Volume

Neural systems involved in the processing of written language have been identified by a number of functional imaging studies. Structural changes in cortical anatomy that occur in the course of literacy acquisition, however, remain largely unknown. Here, we follow elementary school children over their first 2 years of formal reading instruction and use tensor-based morphometry to relate reading proficiency to cortical volume at baseline and follow-up measurement as well as to intraindividual longitudinal volume development between the two measurement time points. A positive relationship was found between baseline gray matter volume in the left superior temporal gyrus and subsequent changes in reading proficiency. Furthermore, a negative relationship was found between reading proficiency at the second measurement time point and intraindividual cortical volume development in the inferior parietal lobule and the precentral and postcentral gyri of the left hemisphere. These results are interpreted as evidence that reading acquisition is associated with preexisting structural differences as well as with experience-dependent structural changes involving dendritic and synaptic pruning.

scholarly journals Structural changes in secondary, but not primary, sensory cortex in individuals with congenital olfactory sensory loss

2019 ◽  
Author(s):  
Moa G. Peter ◽  
Gustav Mårtensson ◽  
Elbrich M. Postma ◽  
Love Engström Nordin ◽  
Eric Westman ◽  
...  
Keyword(s):  
Gray Matter ◽  
Structural Changes ◽  
Gray Matter Volume ◽  
Piriform Cortex ◽  
Sensory Cortex ◽  
Brain Morphology ◽  
Sensory Loss ◽  
Morphological Alterations ◽  
Matter Volume ◽  
Primary Sensory Cortex

ABSTRACTIndividuals with congenital sensory loss usually demonstrate altered brain morphology in areas associated with early processing of the lost sense. Here, we aimed to establish whether this also applies to individuals born without a sense of smell (congenital anosmia) by comparing cortical morphology between 33 individuals with isolated congenital anosmia and matched controls. We detected no structural alterations in the primary olfactory (piriform) cortex. However, individuals with anosmia demonstrated gray matter volume atrophy in bilateral olfactory sulci, explained by decreased cortical area, curvature, and sulcus depth. They further demonstrated increased gray matter volume and cortical thickness in the medial orbital gyri; regions closely associated with olfactory processing, sensory integration, and value-coding. Our results suggest that a lifelong absence of sensory input does not necessarily lead to morphological alterations in primary sensory cortex and extend previous findings with divergent morphological alterations in bilateral orbitofrontal cortex, indicating influences of different plastic processes.

scholarly journals Altered Default Mode Network Is Associated With Cognitive Impairment in Cadasil as Revealed by Multimodal Neuroimaging

2021 ◽  
Author(s):  
Panlong Li ◽  
Qi Huang ◽  
Shiyu Ban ◽  
Yuan Qiao ◽  
Jing Wu ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Gray Matter ◽  
Default Mode Network ◽  
Structural Changes ◽  
Diffusion Tensor ◽  
Small Vessel Disease ◽  
Hippocampal Formation ◽  
Gray Matter Volume ◽  
Default Mode ◽  
Matter Volume

Abstract Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) caused by mutations in NOTCH3 gene is a hereditary cerebral small vessel disease, manifesting with stroke, cognitive impairment and mood disturbances. Functional or structural changes in the default mode network (DMN), which plays important roles in cognitive and mental maintenance, have been found in a number of neurological and mental diseases. However, it is still unclear whether DMN is altered in CADASIL patients.Methods: Multimodal imaging methods, including magnetic resonance imaging (MRI) and positron emission tomography (PET), were applied to evaluate the functional, structural and metabolic characteristics of DMN in 25 CADASIL patients and 42 healthy controls.Results: Compared to controls, CADASIL patients had decreased nodal efficiency and degree centrality of the dorsal medial prefrontal cortex and hippocampal formation within DMN. Structural MRI and diffusion tensor imaging (DTI) showed decreased gray matter volume and fiber tracks presented in the bilateral hippocampal formation. Meanwhile, PET imaging showed decreased metabolism within the whole DMN in CADASIL. Furthermore, correlation analyses showed that these nodal characteristics, gray matter volume, and metabolic signals of DMN were related to cognitive scores in CADASIL.Conclusions: Our results suggested that altered network characteristics of DMN may play important roles in cognitive deficits of CADASIL.

scholarly journals Functional Activation-Informed Structural Changes during Stroke Recovery: A Longitudinal MRI Study

2017 ◽  
Vol 2017 ◽  
pp. 1-13
Author(s):  
Zhiyuan Wu ◽  
Lin Cheng ◽  
Guo-Yuan Yang ◽  
Shanbao Tong ◽  
Junfeng Sun ◽  
...  
Keyword(s):  
Gray Matter ◽  
Structural Changes ◽  
Structural Information ◽  
Gray Matter Volume ◽  
Brain Regions ◽  
Stroke Recovery ◽  
Functional Reorganization ◽  
Matter Volume ◽  
Initial Stage ◽  
Mri Study

Objective. Neuroimaging studies revealed the functional reorganization or the structural changes during stroke recovery. However, previous studies did not combine the functional and structural information and the results might be affected by heterogeneous lesion. This study aimed to investigate functional activation-informed structural changes during stroke recovery. Methods. MRI data of twelve stroke patients were collected at four consecutive time points during the first 3 months after stroke onset. Functional activation during finger-tapping task was used to inform the analysis of structural changes of activated brain regions. Correlation between structural changes in motor-related activated brain regions and motor function recovery was estimated. Results. The averaged gray matter volume (aGMV) of contralesional activated brain regions and laterality index of gray matter volume (LIGMV) increased during stroke recovery, and LIGMV was positively correlated with Fugl-Meyer Index (FMI) at initial stage after stroke. The aGMV of bilateral activated brain regions was negatively correlated with FMI during the stroke recovery. Conclusion. This study demonstrated that combining the stroke-induced functional reorganization and structural change provided new insights into the underlying innate plasticity process during stroke recovery. Significance. This study proposed a new approach to integrate functional and structural information for investigating the innate plasticity after stroke.

scholarly journals Structural MRI Study of the Planum Temporale in Individuals With an At-Risk Mental State Using Labeled Cortical Distance Mapping

2020 ◽  
Vol 11 ◽  
Author(s):  
Yoichiro Takayanagi ◽  
Sue Kulason ◽  
Daiki Sasabayashi ◽  
Tsutomu Takahashi ◽  
Naoyuki Katagiri ◽  
...  
Keyword(s):  
Surface Area ◽  
Gray Matter ◽  
Mental State ◽  
Structural Changes ◽  
Gray Matter Volume ◽  
Planum Temporale ◽  
Healthy Controls ◽  
Matter Volume ◽  
Distance Mapping ◽  
At Risk Mental State

Background: Recent studies have demonstrated brain structural changes that predate or accompany the onset of frank psychosis, such as schizophrenia, among individuals with an at-risk mental state (ARMS). The planum temporale (PT) is a brain region involved in language processing. In schizophrenia patients, gray matter volume reduction and lack of normal asymmetry (left &gt; right) of PT have repeatedly been reported. Some studies showed progressive gray matter reduction of PT in first-episode schizophrenia patients, and in ARMS subjects during their development of psychosis.Methods: MRI scans (1.5 T field strength) were obtained from 73 ARMS subjects and 74 gender- and age-matched healthy controls at three sites (University of Toyama, Toho University and Tohoku University). Participants with ARMS were clinically monitored for at least 2 years to confirm whether they subsequently developed frank psychosis. Cortical thickness, gray matter volume, and surface area of PT were estimated using FreeSurfer-initiated labeled cortical distance mapping (FSLCDM). PT measures were compared among healthy controls, ARMS subjects who later developed overt psychosis (ARMS-P), and those who did not (ARMS-NP). In each statistical model, age, sex, intracranial volume, and scanning sites were treated as nuisance covariates.Results: Of 73 ARMS subjects, 18 developed overt psychosis (12 schizophrenia and 6 other psychoses) within the follow-up period. There were no significant group differences of PT measures. In addition, significant asymmetries of PT volume and surface area (left &gt; right) were found in all diagnostic groups. PT measures did not correlate with the neurocognitive performance of ARMS subjects.Discussion: Our results suggest that the previously-reported gray matter reduction and lack of normal anatomical asymmetry of PT in schizophrenia patients may not emerge during the prodromal stage of psychosis; taken together with previous longitudinal findings, such PT structural changes may occur just before or during the onset of psychosis.

scholarly journals Repetitive T1 Imaging Influences Gray Matter Volume Estimations in Structural Brain Imaging

2021 ◽  
Vol 12 ◽  
Author(s):  
Gregor Broessner ◽  
Isabel Ellerbrock ◽  
Mareike M. Menz ◽  
Florian Frank ◽  
Michael Verius ◽  
...  
Keyword(s):  
Gray Matter ◽  
Structural Changes ◽  
Brain Plasticity ◽  
Longitudinal Design ◽  
Gray Matter Volume ◽  
Anterior Cingulate ◽  
Control Group ◽  
Short Term ◽  
Matter Volume ◽  
Signal Changes

Voxel-based morphometry (VBM) is a widely used tool for studying structural patterns of brain plasticity, brain development and disease. The source of the T1-signal changes is not understood. Most of these changes are discussed to represent loss or possibly gain of brain gray matter and recent publications speculate also about non-structural changes affecting T1-signal. We investigated the potential of pain stimulation to ultra-short-term alter gray matter signal changes in pain relevant brain regions in healthy volunteers using a longitudinal design. Immediately following regional nociceptive input, we detected significant gray matter volume (GMV) changes in central pain processing areas, i.e. anterior cingulate and insula cortex. However, similar results were observed in a control group using the identical time intervals but without nociceptive painful input. These GMV changes could be reproduced in almost 100 scanning sessions enrolling 72 healthy individuals comprising repetitive magnetization-prepared rapid gradient-echo (MPRAGE) sequences. These data suggest that short-term longitudinal repetitive MPRAGE may produce significant GMV changes without any intervention. Future studies investigating brain plasticity should focus and specifically report a consistent timing at which time-point during the experiment the T1-weighted scan is conducted. There is a necessity of a control group for longitudinal imaging studies.

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