Significant Gray Matter Volume Decrease Research Articles

Differential cortical gray matter changes in early- and late-onset patients with amyotrophic lateral sclerosis.

Age at onset may be an important feature associated with distinct subtypes of amyotrophic lateral sclerosis (ALS). Little is known about the neuropathological mechanism of early-onset ALS (EO-ALS) and late-onset ALS (LO-ALS). Ninety ALS patients were divided into EO-ALS and LO-ALS group, and 128 healthy controls were matched into young controls(YCs) and old controls (OCs). A voxel-based morphometry approach was employed to investigate differences in gray matter volume (GMV). Significant age at onset-by-diagnosis interactions were found in the left parietal operculum, left precentral gyrus, bilateral postcentral gyrus, right occipital gyrus, and right orbitofrontal cortex. Post hoc analysis revealed a significant decrease in GMV in all affected regions of EO-ALS patients compared with YCs, with increased GMV in 5 of the 6 brain regions, except for the right orbitofrontal cortex, in LO-ALS patients compared with OCs. LO-ALS patients had a significantly increased GMV than EO-ALS patients after removing the aging effect. Correspondingly, GMV of the left postcentral gyrus correlated with disease severity in the 2 ALS groups. Our findings suggested that the pathological mechanisms in ALS patients with different ages at onset might differ. These findings provide unique insight into the clinical and biological heterogeneity of the 2 ALS subtypes.

Gray matter alterations in tremor-dominant Parkinson's disease after MRgFUS thalamotomy are correlated with tremor improvement: a pilot study.

Regional differences in gray matter volume (GMV) have been reported to be a reliable marker for diagnosing Parkinson's disease (PD). This study aimed to explore the clinical value of GMV to assess magnetic resonance imaging-guided focused ultrasound (MRgFUS) thalamotomy as a treatment for tremor-dominant PD (TDPD). Nine TDPD patients with MRgFUS thalamotomy were recruited for structural magnetic resonance image (MRI) scanning and clinical score evaluation. GMV was calculated. To investigate changes after treatment, voxel- and region of interest (ROI)-wise GMV analyses were performed. Then, GMV with significant differences was extracted from patients to investigate its dynamic alterations by one-way repeated-measures analysis of variance (ANOVA). The nonparametric Spearman rank correlation analysis was used to evaluate the relationship between GMV alterations and tremor improvement after thalamotomy. Tremors were significantly relieved after MRgFUS thalamotomy in nine patients (P<0.05). The treated hand tremor scores improved 74.82% on average in patients from pre-operation to 12 months post-operation. Voxel-wise analysis at the cluster level showed a significant decrease in GMV in the left middle occipital gyrus (MOG) [t=11.81, voxel-level P<0.001, cluster-level Pfamily-wise error (FWE) <0.05] and an increase in GMV in the left precentral gyrus (PreCG) (t=7.99, voxel-level P<0.001, cluster-level PFWE <0.05) in TDPD patients from preoperative to 12 months post-operation, which was significantly correlated with tremor scores (rho =0.346-0.439, P<0.05). ROI-wise analysis showed that GMV related to MRgFUS thalamotomy was associated with long-term structural alterations (P<0.05 with Bonferroni correction), including specific basal ganglia and related nuclei and cerebellum subregions. GMV can be used to reflect tremor improvement after MRgFUS thalamotomy and be helpful to better understand the distant effect of MRgFUS thalamotomy and the involvement of GMV in tremor control in TDPD. ClinicalTrials.gov identifier: NCT04570046.

Brain Network Integrity Changes in Subjective Cognitive Decline: A Possible Physiological Biomarker of Dementia.

Objective: The current study seeks to illustrate potential early and objective neurophysiological biomarkers of neurodegenerative cognitive decline by evaluating features of brain network physiological performance and structure utilizing different modalities.Methods: This study included 17 clinically healthy individuals with self-reported cognitive decline (Subjective Cognitive Decline group, SCD, no objective finding of cognitive decline), 12 individuals diagnosed with amnestic Mild Cognitive Impairment (aMCI), 11 individuals diagnosed with Dementia, and 15 healthy subjects. All subjects underwent computerized cognitive performance testing, MRI scans including T1 for gray matter (GM) volume quantification, DTI for quantification of white matter (WM) microstructure fractional anisotropy (FA) and mean diffusivity (MD), and brain network function evaluation using DELPHI (TMS-EEG) measures of connectivity, excitability, and plasticity.Results: Both DELPHI analysis of network function and DTI analysis detected a significant decrease in connectivity, excitability, and WM integrity in the SCD group compared to healthy control (HC) subjects; a significant decrease was also noted for aMCI and Dementia groups compared to HC. In contrast, no significant decrease was observed in GM volume in the SCD group compared to healthy norms, a significant GM volume decrease was observed only in objectively cognitively impaired aMCI subjects and in dementia subjects.Conclusions: This study results suggest that objective direct measures of brain network physiology and WM integrity may provide early-stage biomarkers of neurodegenerative-related changes in subjects that have not yet displayed any other objective measurable cognitive or GM volume deficits which may facilitate early preventive care for neurodegenerative decline and dementia.

Dynamic gray matter and intrinsic activity changes after epilepsy surgery.

To explore the dynamic changes of gray matter volume and intrinsic brain activity following anterior temporal lobectomy (ATL) in patients with unilateral mesial temporal lobe epilepsy (mTLE) who achieved seizure-free for 2years. High-resolution T1-weighted MRI and resting-state functional MRI data were obtained in ten mTLE patients at five serial timepoints: before surgery, 3, 6, 12, and 24months after surgery. The gray matter volume (GMV) and amplitude of low-frequency fluctuations (ALFF) were compared among the five scans to depict the dynamic changes after ATL. After successful ATL, GMV decreased in several ipsilateral brain regions: ipsilateral insula, thalamus, and putamen showed gradual gray matter atrophy from 3 to 24months, while ipsilateral superior temporal gyrus, middle temporal gyrus, inferior temporal gyrus, middle occipital gyrus, inferior occipital gyrus, caudate nucleus, lingual gyrus, and fusiform gyrus showed significant GMV decrease at 3months follow-up, without further changes. Ipsilateral insula showed gradual ALFF decrease from 3 to 24months after surgery. Ipsilateral superior temporal gyrus showed ALFF decrease at 3months follow-up, without further changes. Ipsilateral thalamus and cerebellar vermis showed obvious ALFF increase after surgery. Surgical resection may lead to a short-term reduction of gray matter volume and intrinsic brain activity in neighboring regions, while the progressive gray matter atrophy may be due to possible intrinsic mechanism of mTLE. Dynamic ALFF changes provide evidence that disrupted focal spontaneous activities were reorganized after successful surgery.

Outcomes at 6 months are related to brain structural and white matter microstructural reorganization in idiopathic tinnitus patients treated with sound therapy

This study aimed to explore brain structural and white matter microstructural reorganization in the early stage of tinnitus and identify brain alterations that contribute to its relief after 6 months of sound therapy. We studied 64 patients with idiopathic tinnitus, including 29 patients who were categorized into an effective group (EG) and 35 who were categorized into an ineffective group (IG) according to the 6‐month follow‐up improvement of the Tinnitus Handicap Inventory score, along with 63 healthy controls (HCs). All participants underwent structural and diffusion tensor imaging scanning on a 3‐T magnetic resonance system. Differences in brain gray/white matter volume and white matter microstructure were evaluated using voxel‐based morphometry analysis and tract‐based spatial statistics among the three groups. Associations between brain reorganization and the improvement of tinnitus symptoms were also investigated. Compared with EG patients, IG patients experienced a significant gray matter volume decrease in the right middle frontal gyrus (MFG)/right precentral gyrus (PreCG). Meanwhile, both EG and IG patients showed significant changes (decrease or increase) in brain white matter integrity in the auditory‐related or nonauditory‐related white matter fiber tracts compared with HCs, while EG patients showed decreased axial diffusivity in the bilateral middle cerebellar peduncle (MCP) compared with IG patients. We combined the gray matter change of the MFG/PreCG and the white matter integrity of the bilateral MCP as an imaging indicator to evaluate the patient's prognosis and screen patients before treatment; this approach reached a sensitivity of 77.1% and a specificity of 82.8%. Our study suggests that there was a close relationship between brain reorganization and tinnitus improvement. The right MFG/PreCG and bilateral MCP may be indicators that can be used to predict prognoses in patients with idiopathic tinnitus and may be used to screen patients before sound therapy. These findings may provide new useful information that can lead to a better understanding of the tinnitus mechanism.

Hippocampal involvement in nonpathological déjà vu: Subfield vulnerability rather than temporal lobe epilepsy equivalent.

IntroductionMorphological correlates of nonpathological déjà vu (DV) have been identified recently within the human brain. Significantly reduced gray matter volume (GMV) within a set of cortical and subcortical regions reported in subjects experiencing DV seems to mirror the distribution of GMV reduction in mesial temporal lobe epilepsy (MTLE) patients but vary in terms of the hippocampus. Another condition associated with hippocampal GMV reduction and DV alike disturbance in memory processing is schizophrenia (SCH). Here, we tested the hypothesis that hippocampal involvement in nonpathological DV resembles more closely the pattern of GMV decrease observed in MTLE compared with that occurring in SCH.MethodsUsing automated segmentation of the MRI data we compared the medians of GMV within 12 specific hippocampal subfields in healthy individuals that do (DV+; N = 87) and do not report déjà vu experience (DV−; N = 26), and patients with MTLE (N = 47) and SCH (N = 29). By Pearson correlation, we then evaluated the similarity of MTLE and SCH groups to DV+ group with respect to spatial distribution of GMV deviation from DV− group.ResultsSignificant GMV decrease was found in MTLE group in most of the subfields. There were just trends in the hippocampal GMV decrease found in DV+ or SCH groups. Concerning the spatial distribution of GMV decrease, we revealed statistically significant correlation for the left hippocampus for SCH vs DV+. Otherwise there was no statistically significant correlation.ConclusionsOur findings reveal structural features of hippocampal involvement in nonpathological DV, MTLE, and SCH. Despite our expectations, the pattern of GMV reduction in the DV+ relative to the DV− group does not resemble the pattern observed in MTLE any more than that observed in SCH. The highly similar patterns of the three clinical groups rather suggest an increased vulnerability of certain hippocampal subfields; namely, Cornu Ammonis (CA)4, CA3, dentate gyrus granular cell layer (GC‐DG), hippocampal–amygdaloid transition area (HATA) and subiculum.

Meta-analysis of voxel-based morphometry studies of gray matter abnormalities in patients with mesial temporal lobe epilepsy and unilateral hippocampal sclerosis.

We aimed to perform a meta-analysis to systematically determine the most consistent regions of gray matter volume (GMV) abnormality in patients of unilateral mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS), and to reveal the difference of GMV abnormality between the patients with left-sided and right-sided MTLE-HS. A comprehensive and systematic search was performed in PubMed for voxel-based morphometry (VBM) studies of MTLE-HS. A total of 12 MTLE-HS studies, including 9 left-sided MTLE-HS (LMTLE-HS) and 8 right-sided MTLE-HS (RMTLE-HS) studies were included. The activation likelihood estimation (ALE) method was applied in our meta-analysis. Compared to the healthy controls, MTLE-HS patients showed significant GMV decrease in the parahippocampal gyrus, left pulvinar and right pyramis. For LMTLE-HS, the most consistent GMV decrease was detected in the left parahippocampal gyrus. For RMTLE-HS, the most consistent GMV decrease was found in the right parahippocampal gyrus. No shared regions of significant GMV reduction were found between LMTLE-HS and RMTLE-HS either. This meta-analysis revealed that MTLE-HS patients had significant GMV reduction even beyond the hippocampus, and the subtypes showed distinct reduction patterns. Our findings, if were further verified with larger samples, would have implications for the clinical diagnosis of MTLE-HS.

Brain Gray Matter Atrophy after Spinal Cord Injury: A Voxel-Based Morphometry Study.

The aim of this study was to explore possible changes in whole brain gray matter volume (GMV) after spinal cord injury (SCI) using voxel-based morphometry (VBM), and to study their associations with the injury duration, severity, and clinical variables. In total, 21 patients with SCI (10 with complete and 11 with incomplete SCI) and 21 age- and sex-matched healthy controls (HCs) were recruited. The 3D high-resolution T1-weighted structural images of all subjects were obtained using a 3.0 Tesla MRI system. Disease duration and American Spinal Injury Association (ASIA) Scale scores were also obtained from each patient. Voxel-based morphometry analysis was carried out to investigate the differences in GMV between patients with SCI and HCs, and between the SCI sub-groups. Associations between GMV and clinical variables were also analyzed. Compared with HCs, patients with SCI showed significant GMV decrease in the dorsal anterior cingulate cortex, bilateral anterior insular cortex, bilateral orbital frontal cortex (OFC), and right superior temporal gyrus. No significant difference in GMV in these areas was found either between the complete and incomplete SCI sub-groups, or between the sub-acute (duration <1 year) and chronic (duration >1 year) sub-groups. Finally, the GMV of the right OFC was correlated with the clinical motor scores of left extremities in not only all SCI patients, but especially the CSCI subgroup. In the sub-acute subgroup, we found a significant positive correlation between the dACC GMV and the total clinical motor scores, and a significant negative correlation between right OFC GMV and the injury duration. These findings indicate that SCI can cause remote atrophy of brain gray matter, especially in the salient network. In general, the duration and severity of SCI may be not associated with the degree of brain atrophy in total SCI patients, but there may be associations between them in subgroups.

Patterns of Gray Matter Abnormalities in Idiopathic Generalized Epilepsy: A Meta-Analysis of Voxel-Based Morphology Studies.

ObjectiveWe aimed to identify the consistent regions of gray matter volume (GMV) abnormalities in idiopathic generalized epilepsy (IGE), and to study the difference of GMV abnormalities among IGE subsyndromes by applying activation likelihood estimation (ALE) meta-analysis.MethodsA systematic review of VBM studies on GMV of patients with absence epilepsy (AE), juvenile myoclonic epilepsy (JME), IGE and controls indexed in PubMed and ScienceDirect from January 1999 to June 2016 was conducted. A total of 12 IGE studies, including 7 JME and 3 AE studies, were selected. Meta-analysis was performed on these studies by using the pooled and within-subtypes analysis (www.brainmap.org). Based on the above results, between-subtypes contrast analysis was carried out to detect the abnormal GMV regions common in and unique to each subtype as well.ResultsIGE demonstrated significant GMV increase in right ventral lateral nucleus (VL) and right medial frontal gyrus, and significant GMV decrease in bilateral pulvinar. For JME, significant GMV increase was seen in right medial frontal gyrus, right anterior cingulate cortex (ACC), while significant GMV decrease was found in right pulvinar. In AE, the most significant GMV increase was found in right VL, and slight GMV reduction was seen in right medial dorsal nucleus, right subcallosal gyrus, left caudate and left precuneus. No overlapped and unique regions with significant GMV abnormalities were found between JME and AE.SignificanceThis meta-analysis demonstrated that thalamo-frontal network was a structure with significant GMV abnormality in IGE, and the IGE subsyndromes showed different GMV abnormal regions. These observations may provide instructions on the clinical diagnosis of IGE.

Contralesional Cortical Structural Reorganization Contributes to Motor Recovery after Sub-Cortical Stroke: A Longitudinal Voxel-Based Morphometry Study.

Although changes in brain gray matter after stroke have been identified in some neuroimaging studies, lesion heterogeneity and individual variability make the detection of potential neuronal reorganization difficult. This study attempted to investigate the potential structural cortical reorganization after sub-cortical stroke using a longitudinal voxel-based gray matter volume (GMV) analysis. Eleven right-handed patients with first-onset, subcortical, ischemic infarctions involving the basal ganglia regions underwent structural magnetic resonance imaging in addition to National Institutes of Health Stroke Scale (NIHSS) and Motricity Index (MI) assessments in the acute (<5 days) and chronic stages (1 year later). The GMVs were calculated and compared between the two stages using nonparametric permutation paired t-tests. Moreover, the Spearman correlations between the GMV changes and clinical recoveries were analyzed. Compared with the acute stage, significant decreases in GMV were observed in the ipsilesional (IL) precentral gyrus (PreCG), paracentral gyrus (ParaCG), and contralesional (CL) cerebellar lobule VII in the chronic stage. Additionally, significant increases in GMV were found in the CL orbitofrontal cortex (OFC) and middle (MFG) and inferior frontal gyri (IFG). Furthermore, severe GMV atrophy in the IL PreCG predicted poorer clinical recovery, and greater GMV increases in the CL OFG and MFG predicted better clinical recovery. Our findings suggest that structural reorganization of the CL “cognitive” cortices might contribute to motor recovery after sub-cortical stroke.

Longitudinal brain structural alterations and systemic inflammation in obstructive sleep apnea before and after surgical treatment.

BackgroundSystemic inflammation, neurocognitive impairments, and morphologic brain changes are associated with obstructive sleep apnea (OSA). Understanding their longitudinal evolution and interactions after surgical treatment provides clues to the pathogenesis of cognitive impairment and its reversibility. In the present study, we investigate clinical disease severity, systemic inflammation, cognitive deficits, and corresponding gray matter volume (GMV) changes in OSA, and the modifications following surgery.MethodsTwenty-one patients with OSA (apnea-hypopnea index, AHI > 5) and 15 healthy volunteers (AHI < 5) underwent serial evaluation, including polysomnography, flow cytometry for leukocyte apoptosis categorization, cognitive function evaluation, and high-resolution brain scan. Disease severity, leukocyte apoptosis, cognitive function, and imaging data were collected to assess therapeutic efficacy 3 months after surgery.ResultsPre-operatively, patients presented with worse cognitive function, worse polysomnography scores, and higher early leukocyte apoptosis associated with increased insular GMV. There was reduced GMV in the anterior cingulate gyrus before and after surgery in the cases compared to that in controls, suggesting an irreversible structural deficit. Post-operatively, there were significant improvements in different cognitive domains, including attention, executive and visuospatial function, and depression, and in early leukocyte apoptosis. There was also a significant decrease in GMVs after treatment, suggesting recovery from vasogenic edema in the precuneus, insula, and cerebellum. Improvement in early leukocyte apoptosis post-surgery predicted better recovery of precuneus GMV.ConclusionsIn OSA, increased disease severity and systemic inflammation can alter GMV in vulnerable regions. Surgical treatment may improve disease severity and systemic inflammation, with subsequent recovery in brain structures and functions.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-016-0887-8) contains supplementary material, which is available to authorized users.

Gray matter volume abnormalities were associated with sustained attention in unmedicated major depression

BackgroundImpaired sustained attention seems to be a core feature of depression while the anatomical alteration of brain was widely reported in depression patients. The authors aimed to identify the relationship between anatomical brain changes and sustained attention deficits in unmedicated patients with major depressive disorder (MDD). MethodsA total of 51 medication-free MDD patients and 51 matched healthy controls (HC) underwent high-resolution structural magnetic resonance imaging scanning, and optimized voxel-based morphometry method was performed to analyze the changes of gray matter volume (GMV). We employed a computerized neurocognitive task from the Cambridge Neuropsychological Tests Automated Battery (CANTAB) – Rapid Visual Information Processing (RVP) task – as a measurement of sustained attention. Based on clinical symptoms, 40 patients who had completed CANTAB-RVP test were divided into MDDa (mild depression patients) and MDDb (severe depression patients) groups. Then the relationships among sustained attention, GMV of different regions and clinical symptoms were explored separately. ResultsMDD patients showed significant GMV increase in left posterior cingulate cortex (PCC) and inferior frontal gyrus (IFG) (p<0.001, uncorrected), and significant GMV decrease in medial/superior frontal gyrus (MFG/SFG) and lingual gyrus (p<0.001, uncorrected). Structure–cognition correlation analyses revealed that in MDD patients, GMV alterations of the IFG were significantly correlated with sustained attention as measured by the CANTAB-RVP. ConclusionsIncreased GMV values of IFG were associated with sustained attention which may underlie the pathophysiology of MDD or be part of the cognition circuit. In the severe depression patients, sustained attention deficits were positively correlated with clinical symptoms.

Gray matter alteration in isolated congenital anosmia patient: a voxel-based morphometry study

Decreased volume of gray matter (GM) was observed in olfactory loss in patients with neurodegenerative disorder. However, GM volume has not yet been investigated in isolated congenital anosmia (ICA) people. We herewith investigated the volume change of gray matter of an ICA boy by morphometric analysis of magnetic resonance images (voxel-based morphometry), and compared with that of 20 age-matched healthy controls. ICA boy presented a significant decrease in GM volume in the orbitofrontal cortex, anterior cingulate cortex, middle cingulate cortex, thalamus, insular cortex, cerebellum, precuneus, gyrus rectus, subcallosal gyrus, middle temporal gyrus, fusiform gyrus and piriform cortex. No significant GM volume increase was detected in other brain areas. The pattern of GM atrophy was similar as previous literature reported. Our results identified similar GM volume alterations regardless of the causes of olfactory impairment. Decreased GM volume was not only shown in olfactory bulbs, olfactory tracts and olfactory sulcus, also in primary olfactory cortex and the secondary cerebral olfactory areas in ICA people. This is the first study to evaluate GM volume alterations in ICA people.

Gray-matter volume reduction in the thalamus and frontal lobe in epileptic patients with generalized tonic-clonic seizures

Generalized tonic-clonic seizures (GTCS) comprise a common subsyndrome of idiopathic generalized epilepsy (IGE). Previous studies found that patients with GTCS had structural abnormalities in a few specific brain regions. However, the underlying clinical cause leading to these abnormalities remains unclear. The present study aimed to explore the relationship between changes in gray-matter (GM) volume and duration of epilepsy, based on GM volume differences observed between GTCS patients and healthy controls. Voxel-based morphometry (VBM) analysis with DARTEL (diffeomorphic anatomical registration through exponential Lie algebra) was used to investigate GM volume differences in 31 GTCS patients compared with 37 age- and gender-matched healthy controls. Voxel-based correlation analysis was used to explore the relationship between GM volume and duration of epilepsy in GTCS patients. Compared with healthy controls, GTCS patients showed significant decreases in GM volume in the bilateral thalami, frontal lobe, insula and cerebellum. In addition, GM volume in the bilateral thalami and left medial frontal gyrus had a negative correlation with duration of epilepsy. GM volume changes in the thalamus and frontal lobe were associated with progressive epileptic seizures. The results indicate the presence of an abnormal thalamocortical network, which may reflect an underlying pathophysiological mechanism of GTCS.