Gray Matter Loss Research Articles

White matter tract-specific microstructural disruption is associated with depressive symptoms in isolated RBD

ObjectiveWhite matter (WM) tract-specific changes may precede gray matter loss in isolated rapid eye movement sleep behavior disorder (iRBD). We aimed to evaluate tract-specific WM changes using tract-specific statistical analysis (TSSA) and their correlation with clinical variables in iRBD patients. MethodsThis was a cross-sectional single-center study of 50 polysomnography-confirmed iRBD patients and 20 age- and sex-matched controls. We used TSSA to identify tract-specific fractional anisotropy (FA) and mean diffusivity (MD) in fourteen major fiber tracts and analyzed between-group differences in these values. Correlations between FA or MD values and clinical variables, including RBD symptom severity, depression and cognition, were evaluated. ResultsPatients with iRBD showed lower FA in the right anterior thalamic radiation (ATR) and higher MD in the bilateral ATR and right inferior fronto-occipital fasciculus (IF-OF) than controls after adjusting for age, sex, and years of education. MD values in the IF-OF positively correlated with scores on the Korean version of the Rapid Eye Movement Sleep Behavior Disorder Questionnaire-Hong Kong (RBDQ-KR, p = 0.042) and the Korean version of the geriatric depression scale (GDS-K, p = 0.002) in iRBD patients. Only GDS-K scores independently correlated with IF-OF MD values after adjusting for RBDQ-KR scores (adjusted p = 0.026). ConclusionThis study suggests WM microstructural disruption in the bilateral ATR and right IF-OF in patients with iRBD and that alterations in the IF-OF may contribute to depressive symptoms.

Increased brain rewiring in patients with mild cognitive impairment

AbstractBackgroundDepending on disease progression, differentiation of patients with mild cognitive impairments from those with Alzheimer disease from structural MRI is often difficult as grey matter (GM) loss is not yet present in MCI patients. Therefore, we re‐assessed WM densities at the initial and changes between two measurements in 22 randomly chosen MCI patients from the ADNI3 cohort [Weiner MW et al. 2017] and compared them to 25 matched controls.MethodWe computed full brain probabilistic tractography by MrTrix3 [Tournier et al. 2019]. ROI to ROI connectivity (HCP MMP 1.0 brain atlas) was compared between groups for Superior Longitudinal Fasciculus (SLF) and Occipital Cortex networks in two longitudinal DTI scans with one year interval by the help of NICARA (www.nicara.eu) [Kopetzky, Butz‐Ostendorf, 2018].ResultSurprisingly, MCI patients showed an increase in brain connectivity of the SLF that was associated with an increased brain rewiring, which we did not observe in matched controls. By contrast, we did not find a similar pattern in WM connections of the visual cortex. This observation was seen in about 40% of MCI patients and did not correlate with age, nor with disease onset. Patients with increased connectivity did not show a decrease in MMSE scores over time whereas patients with a loss in connectivity were more likely to decrease in MMSE score.ConclusionThis study is the first that reports a pronounced brain [Van Ooyen, Butz‐Ostendorf 2017 (eds)] rewiring in association with WM hyperconnectivity [Delli Puzzi et al. 2019] in MCI patients. Phases of pronounced brain rewiring could be an expression of a compensatory response aiming at functional reorganization of brain networks. Our findings point to the urgent need for including longitudinal DTI tractographies in routine brain scans and clinical trials.

Progression in WMH volume is accompanied by higher gray matter loss: One‐year follow‐up MRI study in TATA Longitudinal Study on Aging Cohort of India

AbstractBackgroundSmall vessel disease pathologies such as white matter hyperintensity (WMH) and loss in neuroanatomical volumes with aging have been investigated across various cross‐ sectional and longitudinal‐aging studies in different parts of world. However, it is yet not extensively investigated whether the changes in WMH kinetics over the period impacts the neuroanatomical health? Here, we have measured changes in WMH and neuroanatomic‐volumes, in an ongoing longitudinal study on aging in India called TATA longitudinal study on aging (TLSA), at the baseline and one‐year‐follow‐up visit. The TLSA‐study is a prospective, community‐based, cohort study that comprises of cognitively healthy, educated, and multilingual individuals of both genders aged ≥45 years. The subjects are recruited from urban‐Bangalore, a large metropolitan city in southern India.MethodMRI measurements were conducted on 3T whole‐body‐scanner. MRI study performed close to the first clinical and cognitive‐examination is termed as baseline visit (V0), while MRI close to one‐year follow‐up is termed as V1. T2w‐FLAIR, 3D‐MPRAGE and DWI MRI were performed at both V0‐ and V1‐visits. WMH was quantified using T2w‐FLAIR and MPRAGE‐T1w images. Anatomical volumes were determined using Freesurfer. The volumes were normalized to the total‐intracranial‐volume. Changes in WMH and anatomic volume were calculated as (Volume at V1 – Volume at V0).ResultChanges in WMH and neuroanatomic volumes were evaluated for 128‐subjects who had MRI at both the visits, V0 and V1. Quantification of change in WMH (Delta‐WMH) in the TLSA‐subjects revealed that 65% of the subjects showed progression in WMH‐volume while another 35% did not show WMH‐progression. This indicated that there is a subset of cohorts that showed progression in WMH volume (+0.5‐7.9 ml) while another subset of subjects had no change in WMH over the period. Segmentation of neuroanatomical‐volume showed that the subset of the cohort that showed WNH‐progression over the one‐year period had significantly larger reduction in gray‐matter and increase in CSF volume at V1 compared to another subset that did not had changes in WMH.ConclusionProgression in WMH may be associated with increased vascular insult to the brain resulting in substantial gray‐matter loss and ventricular increase. Increase in WMH volume may fasten the neuroanatomic deteriorations with aging.

Atrophy in dopaminergic pathways is associated with emergence of delusions in patients with Alzheimer’s disease

AbstractBackgroundPeople with advanced Alzheimer’s disease (AD) may present with delusions that are associated with worse quality of life and prognosis. However, early markers of delusions have not been identified yet. The present study aimed to investigate whether differences in cognitive and grey matter (GM) volume decline can be detected in the year before symptom onset between patients with AD who will and will not develop delusions.MethodTwo samples of patients with AD, 63 who will (AD‐D) and 63 who will not develop delusions (AD‐ND) over a year as recorded by means of the NPI, were identified from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database and matched for diagnosis, cognitive status, age, education, sex, handedness and APOE genotype. Sixty‐three additional matched healthy controls (HC) were selected. Group‐by‐time models were used to compare cognitive and clinical data across groups, as well as GM maps by means of VBM. Change in NPI scores was used as covariate. Post hoc analyses were performed to investigate AD‐D vs AD‐ND differences in volume decline in areas found to be more atrophic in the AD‐D group and in brainstem nuclei connected to these areas.ResultNo neurocognitive differences were observed between patient groups either prior to or at symptom onset. When the two patient groups were compared to HC, the AD‐ND showed no greater atrophy over time while greater atrophy in the left caudate was observed in the AD‐D group. Post hoc analyses revealed greater GM loss in the AD‐D group in both caudate bodies and dopaminergic nuclei (i.e. the substantia nigra and the ventral tegmental area), but not in serotoninergic nuclei.ConclusionPatients with AD who will develop delusion showed faster neurodegeneration prior to symptom onset in dopaminergic systems, especially in the nigrostriatal pathway. Therefore, alterations in dopamine neurotransmission due to AD‐related pathology may explain the emergence of delusional thoughts in this population, consistently with the dopaminergic hypothesis of positive symptoms in schizophrenia.

Molecular biomarkers correlate with brain grey and white matter changes in patients with mitochondrial m.3243A > G mutation

IntroductionThe mitochondrial DNA (mtDNA) m.3243A > G mutation in the MT-TL1 gene results in a multi-systemic disease, that is commonly associated with neurodegenerative changes in the brain. MethodsSeventeen patients harboring the m3243A > G mutation were enrolled (age 43.1 ± 11.4 years, 10 M/7F). A panel of plasma biomarkers including lactate acid, alanine, L-arginine, fibroblast growth factor 21 (FGF-21), growth/differentiation factor 15 (GDF-15) and circulating cell free -mtDNA (ccf-mtDNA), as well as blood, urine and muscle mtDNA heteroplasmy were evaluated.Patients also underwent a brain standardized MR protocol that included volumetric T1-weighted images and diffusion-weighted MRI. Twenty sex- and age-matched healthy controls were included. Voxel-wise analysis was performed on T1-weighted and diffusion imaging, respectively with VBM (voxel-based morphometry) and TBSS (Tract-based Spatial Statistics). Ventricular lactate was also evaluated by 1H-MR spectroscopy. ResultsA widespread cortical gray matter (GM) loss was observed, more severe (p < 0.001) in the bilateral calcarine, insular, frontal and parietal cortex, along with infratentorial cerebellar cortex.High urine mtDNA mutation load, high levels of plasma lactate and alanine, low levels of plasma arginine, high levels of serum FGF-21 and ventricular lactate accumulation significantly (p < 0.05) correlated with the reduced brain GM density.Widespread microstructural alterations were highlighted in the white matter, significantly (p < 0.05) correlated with plasma alanine and arginine levels, with mtDNA mutation load in urine, with high level of serum GDF-15 and with high content of plasma ccf-mtDNA. ConclusionsOur results suggest that the synergy of two pathogenic mechanisms, mtDNA-related mitochondrial respiratory deficiency and defective nitric oxide metabolism, contributes to the brain neurodegeneration in m.3243A > G patients.

Is addiction a brain disease? A plea for agnosticism and heterogeneity.

Although increasingly subject to criticism, the brain disease model of addiction (BDMA) remains dominant within addiction science. Yet few advocates or critics of the BDMA have provided an account of what a brain disease is. The aim of this review is to conceptually clarify what it would mean for the BDMA to be true, rather than to argue decisively for or against it. Conceptual clarification of the BDMA requires consideration of possible models of disease and their relationship to the BDMA. A barrier to such consideration is belief that the BDMA is necessary to combatting addiction stigma. To address this barrier, I begin with discussion of what we know about the effects of the brain disease label on addiction stigma, and why labelling effects should have no bearing on the validity of the BDMA. I then distinguish strong, minimal, network, and mismatch models of disease, and I argue that the BDMA aligns with a strong disease model. This means that underlying brain pathology is hypothesized to be the cause of the personal-level observable signs and experienced symptoms characteristic of addiction. Evaluation of the BDMA therefore requires analysis of the concepts of brain dysfunction and causation, and their application to addiction science. Brain dysfunction cannot be analyzed merely as brain changes or brain differences; nor can it be inferred merely from the presence of personal-level signs and symptoms. It is necessary to have an account of normal brain function by which to measure it. The theoretical and empirical challenges to developing such an account are not insurmountable, but they are substantial. Although there exist competing analyses of causation, there is a relatively standard method used to establish it within experimental science: intervention. Using this method, the causal significance of brain states, such as, e.g., extensive gray matter loss and/or neuroadapations in the mesocorticolimbic dopamine system, is not yet fully demonstrated. Further studies are necessary to determine their effect compared with other possible variables, such as, e.g., alternative reinforcers. Conceptual clarification and preliminary empirical assessment of the BDMA recommends agnosticism about its validity and an openness to heterogeneity; in some cases addiction may be a brain disease, in others not. Either way, addiction stigma can be combatted by fighting moralism about drugs and moralistic drug policies directly, as opposed to resting hopes on the brain disease label.

Reduced age-related gray matter loss in the subgenual cingulate cortex in long-term meditators.

Accumulating evidence suggests that meditation practices have positive effects on brain ageing overall. The cingulate is known to be recruited during meditation, but research into possible effects of meditation on the ageing of the cingulate is currently missing. Thus, the present study was designed to help close this knowledge gap, with particular focus on the subgenual cingulate, a region involved in emotional regulation and autonomic and endocrine functions, making it potentially relevant for meditation. Here, we investigated differences in age-related gray matter loss between 50 long-term meditation practitioners (28 male, 22 female), aged between 24 and 77, and 50 age- and sex-matched controls. Areas of interest were four subregions of the subgenual cingulate gyrus (areas 25, 33, s24, and s32) defined as per the Julich-Brain atlas. Our study revealed a significant age-related decline in all subregions in both meditators and controls, but with significantly lower rates of annual tissue loss in meditators, specifically in left and right area s32 and right area 25. These regions have been shown to play a role in mood regulation, autonomic processing, and the integration of emotion and cognitive processes, which are all involved in and impacted by meditation. Overall, the results add further evidence to the emerging notion that meditation may slow the effects of ageing on the brain.

Ageing-related changes in nap neuroscillatory activity are mediated and moderated by grey matter volume.

Ageing‐related changes in grey matter result in changes in the intensity and topography of sleep neural activity. However, it is unclear whether these findings can be explained by ageing‐related differences in sleep pressure or circadian influence. The current study used high‐density electroencephalography to assess how grey matter volume differences between young and older adults mediate and moderate neuroscillatory activity differences during a midday nap following a motor sequencing task. Delta, theta, and sigma amplitude were reduced in older relative to young adults, especially over frontocentral scalp, leading to increases in relative delta frontality and relative sigma lateral centroposteriority. Delta reductions in older adults were mediated by grey matter loss in frontal medial cortex, primary motor cortex, thalamus, caudate, putamen, and pallidum, and were moderated by putamen grey matter volume. Theta reductions were mediated by grey matter loss in primary motor cortex, thalamus, and caudate, and were moderated by putamen and pallidum grey matter volume. Sigma changes were moderated by putamen and pallidum grey matter volume. Moderation results suggested that across frequencies, young adults with more grey matter had increased activity, whereas older adults with more grey matter had unchanged or decreased activity. These results provide a critical extension of previous findings from overnight sleep in a midday nap, indicating that they are not driven by sleep pressure or circadian confounds. Moreover, these results suggest brain regions associated with motor sequence learning contribute to sleep neural activity following a motor sequencing task.

The behavioral variant of frontotemporal dementia: Linking cerebellar MRI alterations to behavioral and affective symptoms

Frontotemporal dementias (FTDs) are progressive neurodegenerative disorders associated with grey matter (GM) loss in frontal and temporal brain regions (Rascovsky et al., 2011) and presenting with marked behavioral symptoms and/or language deficits. The Behavioral variant of FTD (bvFTD) is clinically characterized by insidious changes in personality, interpersonal conduct and emotion processing (Piguet, et al. 2017). Considering its role in higher-level functions (Schmahmann & Sherman, 1998) the cerebellum was recently proposed to be implicated in FTD pathophysiology (Yu Chen et al.,2019) although its specific contribution to bvFTD symptoms still needs to be clarified. Aim of the present study was to assess cerebellar GM changes in patients with bvFTD and their potential association with affective symptoms.

Optical Coherence Tomography and Pattern Electroretinography Changes in Egyptian Patients with Major Depressive Disorder

Abstract Background Major depressive disorder (MDD) is a common psychiatric disorder that affects nearly 11.1-14.6 % of the population in their lifetime. Pathophysiology and brain imaging findings show that degenerative and inflammatory processes may play a role. Meta-analysis of voxel-based morphometry studies in MDD demonstrated significant gray matter loss. From anatomical and embryological perspectives, the retina can be considered a unique extension of the brain and is able to reflect axonal histopathology. Being unmyelinated, it can provide insight into the pathophysiological processes of diseases with a neurodegenerative element. Aim to compare retinal optical coherence tomography (OCT) parameters in a group of MDD patients with a healthy control group and to correlate OCT parameters with pattern electroretinography (PERG) parameters. Method a controlled cross sectional study was conducted on 30 MDD patients and 28 age and sex matched controls. Both groups had a full ophthalmological examination, OCT imaging and 7 patients and 11 controls have PERG recorded. Results Thinning of the superior retinal nerve fiber layer, thinning of most of the ganglion cell inner plexiform (GCIP) layer, thinning of most of the macular thickness and thinning of macular volume in both eyes were detected. There was a statistically significant positive correlation between the left GCIP layer and the amplitude of the N95 wave. Also a statistically significant negative correlation existed between MDD duration in years with the left eye's average volume of the outer ring of the macula. Conclusion Significant retinal changes were detected by OCT in MDD patients supporting the theory of neurodegeneration as a pathophysiology of MDD.

Hypertension With High Homocysteine Is Associated With Default Network Gray Matter Loss.

Hypertension with high homocysteine (Hcy, ≥10 μmol/L) is also known as H-type hypertension (HHT) and proposed as an independent risk factor for stroke and cognitive impairment. Although previous studies have established the relationships among hypertension, Hcy levels, and cognitive impairment, how they affect brain neuroanatomy remains unclear. Thus, we aimed to investigate whether and to what extent hypertension and high Hcy may affect gray matter volume in 52 middle-aged HHT patients and 51 demographically matched normotensive subjects. Voxel-based morphological analysis suggested that HHT patients experienced significant gray matter loss in the default network. The default network atrophy was significantly correlated with Hcy level and global cognitive function. These findings provide, to our knowledge, novel insights into how HHT affects brain gray matter morphology through blood pressure and Hcy.

ProspeCtive study to evaluate efficacy, safety and tOlerability of dietary supplemeNT of Curcumin (BCM95) in subjects with Active relapsing MultIple Sclerosis treated with subcutaNeous Interferon beta 1a 44 mcg TIW (CONTAIN): A randomized, controlled trial

Backgroundmultiple sclerosis (MS) is a complex disease sustained by several pathogenic mechanisms. As such, combination therapy strategies, targeting a range of disease mechanisms, might represent the ideal therapeutic approach. Here we investigated the efficacy of curcumin, a naturally occurring poly-phenolic phytochemical with potent anti-inflammatory and antioxidant properties, in subjects under treatment with IFN β-1a, to test the effects of this combination therapy on clinical and MRI parameters of inflammation and neurodegeneration in relapsing MS (RMS). Methodseighty active RMS were prospectively enrolled, randomized (1:1) to either the IFN-curcumin or the IFN-placebo group and followed up longitudinally with clinical and MRI assessments for 24 months. Primary endpoint was the efficacy of curcumin versus placebo as add-on therapy on new/enlarging T2 lesions in RMS subjects under treatment with subcutaneous IFN β-1a 44 mcg TIW. Efficacy on clinical parameters (relapses and disability progression), other MRI parameters of inflammation (T1 Gd-enhancing lesions, combined unique active-CUA lesions) and neurodegeneration (T1-hypointense lesions, grey matter loss and white matter microstructural damage) as well as safety and tolerability of curcumin were explored as secondary endpoints. Resultsten subjects dropped out from the study by month 12 (6 in the IFN-curcumin group and 4 in the IFN-placebo group), and 27 by month 24 (11 in the IFN-curcumin group and 16 in the IFN-placebo group). Although no between-group difference was present in terms of proportion of subjects free from new/enlarging T2 lesions, a lower proportion of patients with CUA lesions was noted at month 12 in the IFN-curcumin group in comparison with the IFN-placebo group (7.5% vs 17.5%, χ² test p= 0.0167). This result was not confirmed at month 24. The statistical analysis failed to reveal any difference between the two treatment groups – IFN-curcumin and IFN-placebo – in terms of relapses, disability progression, other MRI metrics of inflammation and MRI changes suggestive of ongoing neurodegeneration. No difference in the rate and nature of adverse events was observed between the two treatment groups. ConclusionAlthough the study drop-out rate was too high to allow definite conclusions, our findings suggest that curcumin might add to IFN β-1a efficacy on radiological signs of inflammation in MS, while it did not seem to exert any neuroprotective effect as assessed by clinical and MRI parameters. (NCT01514370)

Brain Structure and Degeneration Staging in Friedreich Ataxia: Magnetic Resonance Imaging Volumetrics from the ENIGMA-Ataxia Working Group.

ObjectiveFriedreich ataxia (FRDA) is an inherited neurological disease defined by progressive movement incoordination. We undertook a comprehensive characterization of the spatial profile and progressive evolution of structural brain abnormalities in people with FRDA.MethodsA coordinated international analysis of regional brain volume using magnetic resonance imaging data charted the whole‐brain profile, interindividual variability, and temporal staging of structural brain differences in 248 individuals with FRDA and 262 healthy controls.ResultsThe brainstem, dentate nucleus region, and superior and inferior cerebellar peduncles showed the greatest reductions in volume relative to controls (Cohen d = 1.5–2.6). Cerebellar gray matter alterations were most pronounced in lobules I–VI (d = 0.8), whereas cerebral differences occurred most prominently in precentral gyri (d = 0.6) and corticospinal tracts (d = 1.4). Earlier onset age predicted less volume in the motor cerebellum (r max = 0.35) and peduncles (r max = 0.36). Disease duration and severity correlated with volume deficits in the dentate nucleus region, brainstem, and superior/inferior cerebellar peduncles (r max = −0.49); subgrouping showed these to be robust and early features of FRDA, and strong candidates for further biomarker validation. Cerebral white matter abnormalities, particularly in corticospinal pathways, emerge as intermediate disease features. Cerebellar and cerebral gray matter loss, principally targeting motor and sensory systems, preferentially manifests later in the disease course.InterpretationFRDA is defined by an evolving spatial profile of neuroanatomical changes beyond primary pathology in the cerebellum and spinal cord, in line with its progressive clinical course. The design, interpretation, and generalization of research studies and clinical trials must consider neuroanatomical staging and associated interindividual variability in brain measures. ANN NEUROL 2021;90:570–583

Grey Matter Loss at Different Stages of Cognitive Decline: A Role for the Thalamus in Developing Alzheimer's Disease.

Background:Alzheimer’s disease (AD) is characterized by cognitive impairment and large loss of grey matter volume and is the most prevalent form of dementia worldwide. Mild cognitive impairment (MCI) is the stage that precedes the AD dementia stage, but individuals with MCI do not always convert to the AD dementia stage, and it remains unclear why.Objective:We aimed to assess grey matter loss across the brain at different stages of the clinical continuum of AD to gain a better understanding of disease progression.Methods:In this large-cohort study (N = 1,386) using neuroimaging data from the Alzheimer’s Disease Neuroimaging Initiative, voxel-based morphometry analyses were performed between healthy controls, individuals with early and late and AD dementia stage.Results:Clear patterns of grey matter loss in mostly hippocampal and temporal regions were found across clinical stages, though not yet in early MCI. In contrast, thalamic volume loss seems one of the first signs of cognitive decline already during early MCI, whereas this volume loss does not further progress from late MCI to AD dementia stage. AD dementia stage converters already show grey matter loss in hippocampal and mid-temporal areas as well as the posterior thalamus (pulvinar) and angular gyrus at baseline.Conclusion:This study confirms the role of temporal brain regions in AD development and suggests additional involvement of the thalamus/pulvinar and angular gyrus that may be linked to visuospatial, attentional, and memory related problems in both early MCI and AD dementia stage conversion.

Hypnic Headache: A Rare Primary Headache Syndrome in an Indian Population with a Mini Review of Literature.

Hypnic headache (HH) is a rare primary headache syndrome first described by Raskin in 1988. To describe the occurrence of HH in Indian patients and compare its clinicoepidemiological features to those published in the literature and attempt to trace some of the evolving concepts regarding its etiology and clinical features since it was first described. Patients attending the neurology outpatient department of a tertiary referral teaching hospital from 01-05-2011 to 30-04-2016 who were identified to have HH as per ICHD 3 beta criteria were included in the study. A meticulous history of the headache and comorbidities, clinical examination, Epworth Sleepiness Scale, blood counts, blood biochemistry, magnetic resonance imaging (MRI) scans of the brain and polysomnography (in selected patients) were done and the results were compared to selected international literature. A total of 11 patients with HH were identified during the study period, of which 8 (72.72%) were males and 3 (27.27%) were females. The age of the patients varied from a minimum of 53 years to a maximum of 78 years (Mean: 63.36, SD: 8.09). The frequency of attacks per month ranged from 5 to 46(Mean: 20.36, SD: 11.67). The duration of each headache episode ranged from a minimum of 30 minutes to a maximum of 4 hours (Mean: 1.93, SD: 1.23). The occurrence of the headaches was maximum during the time periods of 0.00-2.00am and 2.00-4.00am (38% and 36%, respectively). The pain was dull in a majority of patients, 7 (63.63%). Trigeminal autonomic features such as lacrimation, ptosis, or rhinorrhea were not recorded from our cohort. Motor activity was noted in 7 (63.63%) cases. Two (18.18%) patients had associated migraine headaches whereas 3 (27.27%) had associated tension-type headaches. None of the patients in our series had chronic obstructive pulmonary disease. Four (36.36%) patients had systemic hypertension and 1 patient (9.09%) had diabetes mellitus. Two (18.18%) patients had symptoms of obstructive sleep apnea syndrome. Three (27.27%) patients had symptoms of excessive daytime sleepiness according to the Epworth Sleepiness Scale. Blood examinations and MRI were normal in all patients, except for the findings of a few lacunar infarcts and nonspecific T2 weighted hyperintensities in 3 patients (27.27%). Our study proves the existence of the newly described primary headache syndrome called HH in the Indian population. On comparing our results with the international literature, the similarities are much greater than the differences. MRI voxel-based morphometry to demonstrate the loss of gray matter in the posterior hypothalamus may prove to be a reliable test to diagnose primary HH in the future.

Fronto-Parietal Gray Matter Volume Loss Is Associated with Decreased Working Memory Performance in Adolescents with a First Episode of Psychosis.

Cognitive maturation during adolescence is modulated by brain maturation. However, it is unknown how these processes intertwine in early onset psychosis (EOP). Studies examining longitudinal brain changes and cognitive performance in psychosis lend support for an altered development of high-order cognitive functions, which parallels progressive gray matter (GM) loss over time, particularly in fronto-parietal brain regions. We aimed to assess this relationship in a subsample of 33 adolescents with first-episode EOP and 47 matched controls over 2 years. Backwards stepwise regression analyses were conducted to determine the association and predictive value of longitudinal brain changes over cognitive performance within each group. Fronto-parietal GM volume loss was positively associated with decreased working memory in adolescents with psychosis (frontal left (B = 0.096, p = 0.008); right (B = 0.089, p = 0.015); parietal left (B = 0.119, p = 0.007), right (B = 0.125, p = 0.015)) as a function of age. A particular decrease in frontal left GM volume best predicted a significant amount (22.28%) of the variance of decreased working memory performance over time, accounting for variance in age (14.9%). No such association was found in controls. Our results suggest that during adolescence, EOP individuals seem to follow an abnormal neurodevelopmental trajectory, in which fronto-parietal GM volume reduction is associated with the differential age-related working memory dysfunction in this group.

Morphological changes after cranial fractionated photon radiotherapy: Localized loss of white matter and grey matter volume with increasing dose

PurposeNumerous brain MR imaging studies have been performed to understand radiation-induced cognitive decline. However, many of them focus on a single region of interest, e.g. cerebral cortex or hippocampus. In this study, we use deformation-based morphometry (DBM) and voxel-based morphometry (VBM) to measure the morphological changes in patients receiving fractionated photon RT, and relate these to the dose. Additionally, we study tissue specific volume changes in white matter (WM), grey matter (GM), cerebrospinal fluid and total intracranial volume (TIV). Methods and materialsFrom our database, we selected 28 patients with MRI of high quality available at baseline and 1 year after RT. Scans were rigidly registered to each other, and to the planning CT and dose file. We used DBM to study non-tissue-specific volumetric changes, and VBM to study volume loss in grey matter. Observed changes were then related to the applied radiation dose (in EQD2). Additionally, brain tissue was segmented into WM, GM and cerebrospinal fluid, and changes in these volumes and TIV were tested. ResultsPerforming DBM resulted in clusters of dose-dependent volume loss 1 year after RT seen throughout the brain. Both WM and GM were affected; within the latter both cerebral cortex and subcortical nuclei show volume loss. Volume loss rates ranging from 5.3 to 15.3%/30 Gy were seen in the cerebral cortical regions in which more than 40% of voxels were affected. In VBM, similar loss rates were seen in the cortex and nuclei. The total volume of WM and GM significantly decreased with rates of 5.8% and 2.1%, while TIV remained unchanged as expected. ConclusionsRadiotherapy is associated with dose-dependent intracranial morphological changes throughout the entire brain. Therefore, we will consider to revise sparing of organs at risk based on future cognitive and neurofunctional data.

Pattern of cerebellar grey matter loss associated with ataxia severity in spinocerebellar ataxias type 3: a multi-voxel pattern analysis.

Spinocerebellar ataxias type 3 (SCA3) patients are clinically characterized by progressive cerebellar ataxia combined with degeneration of the cerebellum. Previous neuroimaging studies have indicated ataxia severity associated with cerebellar atrophy using univariate methods. However, whether cerebellar atrophy patterns can be used to quantitatively predict ataxia severity in SCA3 patients at the individual level remains largely unexplored. In this study, a group of 66 SCA3 patients and 58 healthy controls were included. Disease duration and ataxia assessment, including theScale for the Assessment and Rating of Ataxia (SARA) and the International Cooperative Ataxia Rating Scale (ICARS), were collected for SCA3 patients. The high-resolution T1-weighted MRI was obtained, and cerebellar grey matter (GM) was extracted using a spatially unbiased infratentorial template toolbox for all participants. We investigated the association between the pattern of cerebellar grey matter (GM) loss and ataxia assessment in SCA3 by using a multivariate machine learning technique. We found that the application of RVR allowed quantitative prediction of both SARA scores (leave-one-subject-out cross-validation: correlation = 0.56, p-value = 0.001; mean squared error (MSE) = 20.51, p-value = 0.001; ten-fold cross-validation: correlation = 0.52, p-value = 0.001; MSE = 21.00, p-value = 0.001) and ICARS score (leave-one-subject-out cross-validation: correlation = 0.59, p-value = 0.001; MSE = 139.69, p-value = 0.001; ten-fold cross-validation: correlation = 0.57, p-value = 0.001; MSE = 145.371, p-value = 0.001) with statistically significant accuracy. These results provide proof-of-concept that ataxia severity in SCA3 patients can be predicted by the alteration pattern of cerebellar GM using multi-voxel pattern analysis.

Regional grey matter microstructural changes and volume loss according to disease duration in multiple sclerosis patients

The spatio-temporal characteristics of grey matter (GM) impairment in multiple sclerosis (MS) are poorly understood. We used a new surface-based diffusion MRI processing tool to investigate regional modifications of microstructure, and we quantified volume loss in GM in a cohort of patients with MS classified into three groups according to disease duration. Additionally, we investigated the relationship between GM changes with disease severity. We studied 54 healthy controls and 247 MS patients classified regarding disease duration: MS1 (less than 5 years, n = 67); MS2 (5–15 years, n = 107); and MS3 (more than15 years, n = 73). We compared GM mean diffusivity (MD), fractional anisotropy (FA) and volume between groups, and estimated their clinical associations. Regional modifications in diffusion measures (MD and FA) and volume did not overlap early in the disease, and became widespread in later phases. We found higher MD in MS1 group, mainly in the temporal cortex, and volume reduction in deep GM and left precuneus. Additional MD changes were evident in cingulate and occipital cortices in the MS2 group, coupled to volume reductions in deep GM and parietal and frontal poles. Changes in MD and volume extended to more than 80% of regions in MS3 group. Conversely, increments in FA, with very low effect size, were observed in the parietal cortex and thalamus in MS1 and MS2 groups, and extended to the frontal lobe in the later group. MD and GM changes were associated with white matter lesion load and with physical and cognitive disability. Microstructural integrity loss and atrophy present differential spatial predominance early in MS and accrual over time, probably due to distinct pathogenic mechanisms that underlie tissue damage.

Infratentorial MRI Findings in Rasmussen Encephalitis Suggest Primary Cerebellar Involvement.

Background and ObjectiveRasmussen encephalitis (RE) is characterized by its unilateral cerebral involvement. However, both ipsi- and contralesional cerebellar atrophy have been anecdotally reported raising questions about the nature and extent of infratentorial findings. Using MRI, we morphometrically investigated the cerebellum and hypothesized abnormalities beyond the effects of secondary atrophy, implicating a primary involvement of the cerebellum by RE.MethodsVoxel-based morphometry of the cerebellum and brainstem was conducted in 57 patients with RE and in 57 matched controls. Furthermore, patient-specific asymmetry indices (AIs) of cerebellar morphometry and fluid-attenuated inversion recovery (FLAIR) intensity were calculated. Using diffusion tensor imaging, the integrity of the cortico-ponto-cerebellar (CPC) tract was assessed. Finally, a spatial independent component analysis (ICA) was used to compare atrophy patterns between groups.ResultsPatients with RE showed bilateral cerebellar and predominantly ipsilesional mesencephalic atrophy (p < 0.01). Morphometric AIs revealed ipsilesional < contralesional asymmetry in 27 and ipsilesional > contralesional asymmetry in 30 patients. In patients with predominant ipsilesional atrophy, morphometric AIs strongly correlated with FLAIR intensity AIs (r = 0.86, p < 0.0001). Fractional anisotropy was lower for ipsilesional-to-contralesional CPC tracts than opposite tracts (T = 2.30, p < 0.05). ICA revealed bilateral and strictly ipsi- and contralesional atrophy components in patients with RE (p < 0.05).DiscussionWe demonstrated atrophy of the ipsilesional-to-contralesional CPC pathway and, consequently, interpret the loss of contralesional gray matter as secondary crossed cerebellar atrophy. The ipsilesional cerebellar atrophy, however, defies this explanation. Based on FLAIR hyperintensities, we interpret ipsilesional atrophy to be due to inflammation in the scope of a primary involvement of the cerebellum by RE.