Cerebral Gray Matter Volume Research Articles

Cortical pattern of reduced perfusion in hearing loss revealed by ASL-MRI.

Age-related hearing loss (HL) can be related to brain dysfunction or structural damage and may result in cerebral metabolic/perfusion abnormalities. Arterial spin labeling (ASL) magnetic resonance imaging (MRI) allows investigating noninvasively brain perfusion changes. Pseudocontinuous ASL and T1-weighted MRI (at 3 T) and neuropsychological testing (Montreal Cognitive Assessment) were performed in 31 HL (age range = 47-77 years, mean age ± SD = 63.4 ± 8.4 years, pure-tone average [PTA] HL > 50 dB) and 28 normal hearing (NH; age range = 48-78 years, mean age ± SD = 59.7 ± 7.4 years) subjects. Cerebral blood flow (CBF) and gray matter volume (GMV) were analyzed in the cortical volume to assess perfusion and structural group differences. Two HL subjects showing cognitive impairment were excluded from group comparisons. No significant differences in either global or local atrophy were detected between groups but the HL group exhibited significant regional effects of reduced perfusion within the bilateral primary auditory cortex, with maximal CBF difference (-17.2%) in the right lateral Heschl's gyrus. For the whole sample of HL and NH subjects (n = 59 = 31 HL + 28 NH), the regional CBF was correlated positively to the regional GMV (p = 0.020). In HL subjects (n = 31), the regional CBF was correlated negatively to the audiogram steepness (frequency range: 2-4 kHz, right ear: p = 0.022, left ear: p = 0.015). The observed cortical pattern of perfusion reduction suggests that neuronal metabolism can be related to HL before the recognition of brain structural damage. This also illustrates the potential of ASL-MRI to contribute early functional markers of reduced central processing associated with HL.

Emergent Prophylactic, Reparative and Restorative Brain Interventions for Infants Born Preterm With Cerebral Palsy.

Worldwide, an estimated 15 million babies are born preterm (<37 weeks' gestation) every year. Despite significant improvements in survival rates, preterm infants often face a lifetime of neurodevelopmental disability including cognitive, behavioral, and motor impairments. Indeed, prematurity remains the largest risk factor for the development of cerebral palsy. The developing brain of the preterm infant is particularly fragile; preterm babies exhibit varying severities of cerebral palsy arising from reductions in both cerebral white and gray matter volumes, as well as altered brain microstructure and connectivity. Current intensive care therapies aim to optimize cardiovascular and respiratory function to protect the brain from injury by preserving oxygenation and blood flow. If a brain injury does occur, definitive diagnosis of cerebral palsy in the first few hours and weeks of life is difficult, especially when the lesions are subtle and not apparent on cranial ultrasound. However, early diagnosis of mildly affected infants is critical, because these are the patients most likely to respond to emergent treatments inducing neuroplasticity via high-intensity motor training programs and regenerative therapies involving stem cells. A current controversy is whether to test universal treatment in all infants at risk of brain injury, accepting that some patients never required treatment, because the perceived potential benefits outweigh the risk of harm. Versus, waiting for a diagnosis before commencing targeted treatment for infants with a brain injury, and potentially missing the therapeutic window. In this review, we discuss the emerging prophylactic, reparative, and restorative brain interventions for infants born preterm, who are at high risk of developing cerebral palsy. We examine the current evidence, considering the timing of the intervention with relation to the proposed mechanism/s of action. Finally, we consider the development of novel markers of preterm brain injury, which will undoubtedly lead to improved diagnostic and prognostic capability, and more accurate instruments to assess the efficacy of emerging interventions for this most vulnerable group of infants.

Pregnancy and adolescence entail similar neuroanatomical adaptations: A comparative analysis of cerebral morphometric changes

Mapping the impact of pregnancy on the human brain is essential for understanding the neurobiology of maternal caregiving. Recently, we found that pregnancy leads to a long-lasting reduction in cerebral gray matter volume. However, the morphometric features behind the volumetric reductions remain unexplored. Furthermore, the similarity between these reductions and those occurring during adolescence, another hormonally similar transitional period of life, still needs to be investigated. Here, we used surface-based methods to analyze the longitudinal magnetic resonance imaging data of a group of 25 first-time mothers (before and after pregnancy) and compare them to those of a group of 25 female adolescents (during 2 years of pubertal development). For both first-time mothers and adolescent girls, a monthly rate of volumetric reductions of 0.09 mm3 was observed. In both cases, these reductions were accompanied by decreases in cortical thickness, surface area, local gyrification index, sulcal depth, and sulcal length, as well as increases in sulcal width. In fact, the changes associated with pregnancy did not differ from those that characterize the transition during adolescence in any of these measures. Our findings are consistent with the notion that the brain morphometric changes associated with pregnancy and adolescence reflect similar hormonally primed biological processes.

Genetic and environmental influences on structural brain measures in twins with autism spectrum disorder

Atypical growth patterns of the brain have been previously reported in autism spectrum disorder (ASD) but these alterations are heterogeneous across individuals, which may be associated with the variable effects of genetic and environmental influences on brain development. Monozygotic (MZ) and dizygotic (DZ) twin pairs with and without ASD (aged 6–15 years) were recruited to participate in this study. T1-weighted MRIs (n = 164) were processed with FreeSurfer to evaluate structural brain measures. Intra-class correlations were examined within twin pairs and compared across diagnostic groups. ACE modeling was also completed. Structural brain measures, including cerebral and cerebellar gray matter (GM) and white matter (WM) volume, surface area, and cortical thickness, were primarily influenced by genetic factors in TD twins; however, mean curvature appeared to be primarily influenced by environmental factors. Similarly, genetic factors accounted for the majority of variation in brain size in twins with ASD, potentially to a larger extent regarding curvature and subcortical GM; however, there were also more environmental contributions in twins with ASD on some structural brain measures, such that cortical thickness and cerebellar WM volume were primarily influenced by environmental factors. These findings indicate potential neurobiological outcomes of the genetic and environmental risk factors that have been previously associated with ASD and, although preliminary, may help account for some of the previously outlined neurobiological heterogeneity across affected individuals. This is especially relevant regarding the role of genetic and environmental factors in the development of ASD, in which certain brain structures may be more sensitive to specific influences.

Reduced gray matter volume in cognitively preserved COMT 158Val/Val Parkinson's disease patients and its association with cognitive decline.

The COMT Val158Met polymorphism has recently been identified as a predictor for cognitive decline in Parkinson's disease (PD). However, it remains unknown whether an early brain structural compromise could be involved in this clinical association. Here, in a cohort of 120 cognitively preserved de novo PD patients from the Parkinson's Progression Markers Initiative (PPMI) database, we found a widespread reduction in cerebral gray matter volume (GMV) in patients harboring the Val/Val genotype. The atrophic pattern included fronto-subcortical and parieto-temporal territories. Importantly, the GMV at some of the identified regions was associated with cognitive decline in a 4-year follow-up period. These findings suggest that GMV compromise in the early stages of PD may be a predisposing factor for cognitive decline of COMT Val/Val homozygotes.

Structural brain changes in perinatally HIV-infected young adolescents in South Africa

To describe the structural brain changes, neurocognitive and mental health associations in adolescents perinatally infected with HIV-1 infection. Cross-sectional. Two hundred and four adolescents with perinatally acquired HIV and 44 uninfected frequency-matched controls aged 9-11 years were enrolled within the Cape Town Adolescent Antiretroviral Cohort. Diffusion tensor imaging and structural brain MRI was done to determine fractional anisotropy, mean diffusivity, grey and white matter volumes, cortical thickness and cortical surfractional anisotropy area. Correlation coefficients were calculated between total grey and white matter volume, cortical surface area, cortical thickness, whole brain fractional anisotropy and whole brain mean diffusivity and clinical and laboratory parameters including general intellectual functioning, Becks Youth Inventory, Child Motivation Scale and Child Behaviour Checklist. HIV-infected adolescents performed worse than controls on the Wechsler Abbreviated Scale of Intelligence (WASI; P < 0.01). HIV-infected adolescents had significant fractional anisotropy decreases, mean diffusivity increases and decreases in cerebral grey matter volumes, cortical surface area and decreased gyrification. Whole-brain mean fractional anisotropy was significantly reduced in the HIV-infected group (P = 0.031). There were significant correlation coefficients between greater total grey (P = 0.008) and white matter volume (P = 0.004) with the WASI and the Becks self-concept subscale (P = 0.038). Lower whole brain fractional anisotropy was associated with higher scores on the Becks anger (P = 0.018) and disruptive behaviour subscales (P = 0.031). Higher whole brain mean diffusivity was associated with apathy (P = 0.046). The pattern of increased risk of white matter microstructure alterations, smaller grey matter volumes, reduced cortical surface area and decreased gyrification, suggests abnormal neurodevelopment in perinatally infected younger adolescents.

Effect of mood stabilizer on gray matter volume in patients with bipolar disorder I

Objective To investigate the abnormal change of gray matter volume in patients with euthymic bipolar disorder I (BD-I), and to elucidate the relationship between the use of different mood stabilizers and brain structure variations. Methods Voxel-based morphometry (VBM) was used to analyze the volume of local gray matter in 35 patients with BD-I and 30 healthy controls(HC). The patients were divided into BD-I with lithium group and BD-I with valproate group according to different mood stabilizers.The volume differences of gray matter of the three groups were compared by one-way ANOVA. Results Compared with HC, BD-I patients showed significantly reduced gray matter volume in the medial frontal cortex (MNI(x, y, z): 2, 34, -18), orbital frontal cortex (MNI(x, y, z): -32, 22, -4), frontal operculum (MNI(x, y, z): 38, 18, 4) and insula cortex (MNI(x, y, z): -32, 22, -4)(P 0.05). Conclusion Emotional disturbance in patients with BD-I may be associated with reduced gray matter volume in the medial frontal cortex, orbital frontal cortex, frontal operculum and insula cortex.There are not significant difference about the effects of lithium carbonate and valproate on cerebral gray matter volume in patients with BD-I. Key words: Bipolar disorder; Voxel-based morphology; Mood stabilizer

Association between physical fitness and cerebral grey matter integrity in patients suffering from Parkinson's disease, a structural MRI study

Being physically active protects the elders against cerebral grey matter (GM) loss in regions particularly exposed to aging [1] . This cross-sectional study extended this hypothesis by searching correlations between volume or microstructure of GM and physical fitness in the nigrostriatal system of patients suffering from Parkinson's disease (PPD). Cerebral grey matter volume (GMV), magnetization transfer (MT) and R2* (an index of local iron) parameters were extracted from whole brain 3 T MRI and were analysed voxel-by-voxel using SPM12 in 42 PPD and 32 matched healthy controls (HC). All subjects were also tested for Peak work load (PWL) and knee flexor strength (KFS). First, we performed a two-sample t -test to look at areas affected in the nigrostriatal system of the PPD in comparison to HC. Next, we used a regression analysis to test which of these regions, if any, showed a relationship between (1) GMV, MT or R2* and (2) individual PWL or KFS. The comparative study showed increased R2* in bilateral SN, reduced GMV and increased R2* in left and right striata ( P uncorrected < 0.001). In PPD, GMV in the head of the right caudate nucleus and anterior putamen showed a positive correlation with PWL and GMV ( P corrected < 0.023). Besides, GMV in this cluster also correlated with global cognitive performance assessed by the Mattis Dementia Rating Scale ( P corrected < 0.024). None of the disturbed regions correlated with KFS. No significant correlations were observed in these regions for HC. Aerobic fitness may have a specific neuroprotective effect on the right anterior striatum of PPD, and this could be associated with better cognition.

An Association Study on the Cognitive Function and the Cerebral Grey Matter Volume of Patients with First-Episode Schizophrenia.

BackgroundThe impairment of cognitive function is one of the core symptoms in schizophrenia, and the degree of recovery is closely related to whether patients are able to rejoin society successfully.ObjectiveThis study was to clarify the correlation between cognitive function and cerebral grey matter volume in schizophrenia.MethodsThe neuro-cognitive functions of thirty-seven patients with first-episode schizophrenia (the patient group) and thirty healthy controls (the control group) was evaluated with the Clock Drawing Test, Trail Marking Test, Digit Span Test, Auditory Verbal Learning Test, Wisconsin Card Sorting Test, Verbal Fluency Test, Semantic Similarity Test and Stroop Color-Word Test. The facial emotion cognitive task was employed to assess the facial emotion cognitive functions of thirty-two patients with first-episode schizophrenia (the patient group) and 29 healthy controls (the control group). The psychotic symptoms of patients with first-episode schizophrenia were evaluated using the Positive and Negative Syndrome Scale (PANSS). The brain imaging data of the patient group and control group were collected using the magnetic resonance imagine (MRI).ResultsThe difference between the patient group and the control group in the results of Clock Drawing Test, Trail Marking Test, Digit Span Test, Auditory Verbal Learning Test, Wisconsin Card Sorting Test, Verbal Fluency Test, Semantic Similarity Test and Stroop Color-Word Test’s reaction time were significant. These two groups’ Slopes in the facial emotion cognitive task were also significantly different from each other. According to the comparison of cerebral grey matter volume between the patient group and the control group, it was found that the grey matter volume of the patient group increased in the left superior frontal gyrus, and decreased in the left occipital gyrus, lingual gyrus and upper cerebellum. Based on the analyses of neuro-cognitive data and brain imaging data of the patient group, the scores of the number of correct responses in Stroop Color-Word Test’s Card C were negatively correlated with grey matter volumes of the left upper frontal gyrus, right upper frontal gyrus and middle frontal gyrus. The analyses on the facial emotion cognitive task and brain imaging data of the patient group showed that the slope data were positively correlated with grey matter volumes of the right superior temporal gyrus, middle temporal gyrus, left middle temporal gyrus, inferior temporal gyrus and fusiform gyrus.ConclusionThere are general impairments in the neuro-cognitive functions and facial emotion cognitive functions of patients with first-episode schizophrenia, and the results suggest that brain areas with abnormal grey matter volumes are likely to be the brain structure and functional basis of the cognitive impairments.

Relationships between cerebral structure and cognitive function in African Americans with type 2 diabetes

BackgroundRelationships between cognitive function and brain structure remain poorly defined in African Americans with type 2 diabetes. MethodsCognitive testing and cerebral magnetic resonance imaging in African Americans from the Diabetes Heart Study Memory IN Diabetes (n = 480) and Action to Control Cardiovascular Risk in Diabetes MIND (n = 104) studies were examined for associations. Cerebral gray matter volume (GMV), white matter volume (WMV) and white matter lesion volume (WMLV) and cognitive performance (Mini-mental State Exam [MMSE and 3MSE], Digit Symbol Coding (DSC), Stroop test, and Rey Auditory Verbal Learning Test) were recorded. Multivariable models adjusted for age, sex, BMI, scanner, intracranial volume, education, diabetes duration, HbA1c, LDL-cholesterol, smoking, hypertension and cardiovascular disease assessed associations between cognitive tests and brain volumes by study and meta-analysis. ResultsMean(SD) participant age was 60.1(7.9) years, diabetes duration 12.1(7.7) years, and HbA1c 8.3(1.7)%. In the fully-adjusted meta-analysis, lower GMV associated with poorer global performance on MMSE/3MSE (β̂ = 7.1 × 10−3, SE 2.4 × 10−3, p = 3.6 × 10−3), higher WMLV associated with poorer performance on DSC (β̂ = −3 × 10−2, SE 6.4 × 10−3, p = 5.2 × 10−5) and higher WMV associated with poorer MMSE/3MSE performance (β̂ = −7.1 × 10−3, SE = 2.4 × 10−3, p = 3.6 × 10−3). ConclusionsIn African Americans with diabetes, smaller GMV and increased WMLV associated with poorer performance on tests of global cognitive and executive function. These data suggest that WML burden and gray matter atrophy associate with cognitive performance independent of diabetes-related factors in this population.

Alzheimer Disease and Mild Cognitive Impairment: Integrated Pulsed Arterial Spin-Labeling MRI and 18F-FDG PET.

Purpose To compare PET/MR hypoperfusion and hypometabolism in patients with Alzheimer disease (AD) and mild cognitive impairment (MCI) compared with healthy control (HC) participants. Materials and Methods Maps of cerebral blood flow (CBF; pulsed arterial spin-labeling [ASL] MRI), glucose metabolism (fluorine 18 [18F] fluorodeoxyglucose [FDG] PET), and gray matter (GM) volume (structural T1-weighted MRI) were calculated from integrated PET/MR data in 45 patients with AD (mean age, 69 years ± 9 [standard deviation]; age range, 51-89 years), 20 patients with MCI (mean age, 64 years ± 10; age range, 45-82 years), and 11 HC participants (mean age, 65 years ± 8; age range, 54-80 years) between 2011 and 2014. After preprocessing, voxel-wise analyses of variance, volume of interest, and independent component analyses were performed for comparisons of CBF and glucose metabolism. Results Analyses revealed high overlap between components, regional and quantitative hypoperfusion, and hypometabolism in patients with AD compared with HC participants in precuneus, parietal, temporal, and occipital cortex. In patients with MCI compared with HC participants, FDG PET exclusively demonstrated quantitative hypometabolism and a component in the precuneus. Volume-of-interest analysis in global GM in patients with AD compared with HC participants showed lower CBF (42 mL/100 g per minute ± 8 vs 49 mL/100 g per minute ± 7, respectively; P = .035) and lower FDG uptake (0.8 ± 0.1 vs 1 ± 0.1, respectively; P < .001). Conclusion In patients with AD, pulsed ASL MRI revealed regional and quantitative abnormalities and components similar to 18F-FDG PET with a reduced extent. In patients with MCI, 18F-FDG PET exclusively demonstrated quantitative hypometabolism and a component in the precuneus, indicating higher sensitivity to detect preclinical AD compared with the currently used pulsed ASL MRI sequence.

Volumetric brain analysis as a predictor of a worse cognitive outcome in Parkinson's disease

Cognitive impairment in Parkinson's disease (PD) results in significant morbidity and mortality being early diagnosis essential. Identification of patients who are at higher risk of developing cognitive impairment based only on clinical data is not sufficient. To this end, magnetic resonance imaging (MRI) with automatic segmentation, such as FreeSurfer, could be a useful tool with high accuracy because it has histological validation. ObjectivesThe objective of this study was to evaluate clinical, neuropsychological and FreeSurfer variables that may be related to worse cognitive outcomes over 18 months in PD patients compared with controls. MethodsPD patients were recruited according to established inclusion and exclusion criteria as well individuals without any neurological or psychiatric diagnosis and were submitted to the same protocol: neurological, neuropsychological and neuroimaging evaluations. After 18 months, the study subjects were reassessed by neurological and neuropsychological evaluations. ResultsOf 171 individuals selected for first evaluation, 96 concluded the study during 18-month follow-up. The PD group presented worse performance in the neuropsychological assessment during both the initial and final evaluations. The results obtained by FreeSurfer revealed a significant reduction (unilateral or bilateral) in the volume of thalamus, caudate nucleus, putamen, hippocampus, amygdala, accumbens, corpus callosum and cerebral gray matter in the PD group. A worse cognitive outcome was more prevalent in the PD group. ConclusionsWorse cognitive performance documented by neuropsychological assessment in the PD group was correlated with reduced volume of several structures by FreeSurfer analysis and may be a biomarker of cognitive decline.

Sleep-related brain atrophy and disrupted functional connectivity in older adults

Aging associates with sleep dysfunction as well as brain alterations. However, the association between age-related brain alterations and their subjective sleep changes is less understood. To address this issue, we recorded T1 weighted structural and resting-state functional magnetic resonance imaging from both young (n = 62) and older adults (n = 108). In addition, all participants completed a battery of psychometric tests, including the Pittsburg Sleep Quality Index. We found that the age-related atrophy of cerebral gray matter, hippocampal and thalamic volume were associated with subjective sleep decline, and the atrophy of cerebral gray matter mediated the age effect on sleep. In addition, older adults exhibited decreased functional connectivity within the medial temporal lobe subsystem than their young counterparts. Moreover, there is a significant positive association between sleep and functional connectivity in young but not in older adults. In light of our findings, we suggest a neuropathological model in which age-related brain alterations may partially explain the well-documented declines in sleep with aging.

Abstract 025: Cross-sectional Relations of Serum Cortisol and Cognitive and Structural Brain Measures in Young Adults: The Framingham Heart Study

Introduction: Chronic stress and related changes in serum cortisol have adverse effects on brain structure and cognition in animal models. However, evidence from population-based studies is scant. We assessed the association of early morning serum cortisol with cognition and brain structural integrity in middle-aged adults without dementia. Hypotheses: High or low levels of serum cortisol are associated with lower cognitive performance and brain volumes. Methods: We evaluated dementia-free Framingham Study (Generation 3) participants (mean age 48.5 years; 46.8% men), who underwent cognitive testing of memory, abstract reasoning, visual perception, attention, and executive function (n= 2231), and brain MRI (n=2018) to assess total white matter, lobar gray matter, and white matter hyperintensity volumes and fractional anisotropy (FA) measures. We used linear or logistic (cortisol categorized in tertiles, middle tertile as the reference) regression to assess the relations of cortisol with cognition, MRI volumes and voxel-based microstructural white matter integrity and gray matter density, adjusting for age, sex, APOE and vascular risk factors. Results: Higher cortisol (highest tertile vs. middle tertile) was associated with worse memory and visual perception, as well as lower total cerebral brain, occipital and frontal lobar gray matter volumes (Table ) . Higher cortisol was associated with multiple areas of microstructural changes on voxel-based analyses (gray matter density and FA). The association of cortisol with total cerebral brain volume varied by sex ( Pinteraction =0.048 , highest cortisol tertile inversely associated with cerebral brain volume in women [ P= 0.001] but not in men [ P =0.717]). There was no effect modification by the apoE4 genotype of the relations of cortisol and cognition or imaging traits. Conclusions: Higher serum cortisol was associated with lower brain volumes and impaired memory in asymptomatic young adults in their forties; women may be particularly susceptible to this influence.

Cerebral gray matter volume losses in essential tremor: A case-control study using high resolution tissue probability maps

IntroductionEssential tremor (ET) is increasingly recognized as a multi-dimensional disorder with both motor and non-motor features. For this reason, imaging studies are more broadly examining regions outside the cerebellar motor loop. Reliable detection of cerebral gray matter (GM) atrophy requires optimized processing, adapted to high-resolution magnetic resonance imaging (MRI). We investigated cerebral GM volume loss in ET cases using automated segmentation of MRI T1-weighted images. MethodsMRI was acquired on 47 ET cases and 36 controls. Automated segmentation and voxel-wise comparisons of volume were performed using Statistical Parametric Mapping (SPM) software. To improve upon standard protocols, the high-resolution International Consortium for Brain Mapping (ICBM) 2009a atlas and tissue probability maps were used to process each subject image. Group comparisons were performed: all ET vs. Controls, ET with head tremor (ETH) vs. Controls, and severe ET vs. Controls. An analysis of variance (ANOVA) was performed between ET with and without head tremor and controls. Age, sex, and Montreal Cognitive Assessment (MoCA) score were regressed out from each comparison. ResultsWe were able to consistently identify regions of cerebral GM volume loss in ET and in ET subgroups in the posterior insula, superior temporal gyri, cingulate cortex, inferior frontal gyri and other occipital and parietal regions. There were no significant increases in GM volume in ET in any comparisons with controls. ConclusionThis study, which uses improved methodologies, provides evidence that GM volume loss in ET is present beyond the cerebellum, and in fact, is widespread throughout the cerebrum as well.

Brain gray matter alterations in Chinese patients with chronic knee osteoarthritis pain based on voxel-based morphometry.

Altered cerebral gray matter volume (GMV) is commonly found in patients with chronic pain. Chronic pain is the prominent characteristic of knee osteoarthritis (KOA), yet little is known about its morphological changes in the brain. Here an MRI study was performed to examine the structural brain abnormalities in 30 KOA patients with knee pain and age-matched healthy subjects. We detected that the patients exhibited significant almost 2-fold age-related decreases of GMV compared to healthy controls. Moreover, KOA patients also had significant loss of regional GMV including in the bilateral orbital frontal cortex (OFC), the right lateral prefrontal cortex (lPFC), and precentral and postcentral cortices. In addition, a high proportion of KOA patients exerted abnormal scores of Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Scale (HAMA), Mini Mental State examination (MMSE), and Montreal Cognitive Assessment (MoCA) compare to controls. Our results imply that chronic pain conditions which preferentially involve PFC might consider as a “cognitive state.” And emotion and cognitive function about chronic pain should be highly regarded.

Clinical Perspectives of Lithium's Neuroprotective Effect.

Evidence for a neuroprotective effect of lithium has accumulated over the last 2 decades, and this phenomenon has been regarded as an important mechanism of lithium action in mood disorders. It has been reflected by an increase in cerebral gray matter volume in lithium-treated subjects and by the favorable influence of lithium on cognitive functions. A neuroprotective effect of lithium also makes this ion a possible candidate for use as a therapeutic drug in neurology, especially in neurodegenerative disorders. In this paper, neurochemical mechanisms of neuroprotective action of lithium will be characterized. A possible association between the effect of lithium on brain structures reflected in neuroimaging studies, as well as on cognitive functions, and its neuroprotective action, will be considered. Data from experimental, epidemiological, and clinical studies have also pointed to an antidementia effect of lithium, bringing about some promise of using lithium in the treatment of mild cognitive impairment and Alzheimer's disease. The results of attempts of employing lithium in other neurodegenerative disorders will also be discussed.

Cerebral gray matter volume in patients with chronic migraine: correlations with clinical features

BackgroundTo date, few MRI studies have been performed in patients affected by chronic migraine (CM), especially in those without medication overuse. Here, we performed magnetic resonance imaging (MRI) voxel-based morphometry (VBM) analyses to investigate the gray matter (GM) volume of the whole brain in patients affected by CM. Our aim was to investigate whether fluctuations in the GM volumes were related to the clinical features of CM.MethodsTwenty untreated patients with CM without a past medical history of medication overuse underwent 3-Tesla MRI scans and were compared to a group of 20 healthy controls (HCs). We used SPM12 and the CAT12 toolbox to process the MRI data and to perform VBM analyses of the structural T1-weighted MRI scans. The GM volume of patients was compared to that of HCs with various corrected and uncorrected thresholds. To check for possible correlations, patients’ clinical features and GM maps were regressed.ResultsInitially, we did not find significant differences in the GM volume between patients with CM and HCs (p < 0.05 corrected for multiple comparisons). However, using more-liberal uncorrected statistical thresholds, we noted that compared to HCs, patients with CM exhibited clusters of regions with lower GM volumes including the cerebellum, left middle temporal gyrus, left temporal pole/amygdala/hippocampus/pallidum/orbitofrontal cortex, and left occipital areas (Brodmann areas 17/18). The GM volume of the cerebellar hemispheres was negatively correlated with the disease duration and positively correlated with the number of tablets taken per month.ConclusionNo gross morphometric changes were observed in patients with CM when compared with HCs. However, using more-liberal uncorrected statistical thresholds, we observed that CM is associated with subtle GM volume changes in several brain areas known to be involved in nociception/antinociception, multisensory integration, and analgesic dependence. We speculate that these slight morphometric impairments could lead, at least in a subgroup of patients, to the development and continuation of maladaptive acute medication usage.

Temporal gradient during famous face naming is associated with lower cerebral blood flow and gray matter volume in aging

ObjectiveEvidence suggests that famous face naming may be a cognitive ability especially sensitive to the early pathological processes of Alzheimer's disease (AD) and that those at risk for AD may demonstrate a Ribot temporal gradient (RTG), characterized by better performance for naming remote famous faces than for naming recent famous faces. Reductions in cerebral blood flow (CBF) and gray matter volume (GMV) have been implicated in the neuropathological cascade of AD and show utility as biomarkers of AD risk. We examined whether a RTG during famous face naming was associated with lower CBF and/or GMV among a group of cognitively normal older adults. MethodsVoxel-wise independent samples t-tests were employed to contrast resting CBF values between those who exhibited a RTG (RTG+) during a famous face naming task and those who did not (RTG-) among a sample of 52 cognitively normal older adults (25 RTG-, 27 RTG+; mean age = 73). Groups were also compared on GMV using a voxel-wise general linear model. ResultsSignificant group differences in CBF and GMV were found, whereby the RTG+ group demonstrated reduced CBF and GMV within medial temporal lobe regions (hippocampus, parahippocampal gyrus), relative to the RTG- group. ConclusionsThis represents the first study to show that cognitively intact older adults who demonstrate a RTG during famous face naming exhibit vascular dysregulation and structural changes similar to that seen in AD risk. Findings suggest that famous face naming ability may be particularly sensitive to the very early brain changes associated with AD.

A two-year study using cerebral gray matter volume to assess the response to fingolimod therapy in multiple sclerosis

BackgroundCerebral gray matter (GM) atrophy has clinical relevance in multiple sclerosis (MS). Fingolimod has known efficacy on clinical and conventional MRI findings in MS; the effect on GM is unknown. ObjectiveTo explore fingolimod's treatment effect on cerebral GM atrophy over two years in patients with relapsing forms of MS. Design/methodsPatients starting fingolimod [n=24, age (mean±SD) 41.2±11.6years, Expanded Disability Status Scale (EDSS) score 1.1±1.4; 58% women] were compared to untreated patients [n=29, age 45.7±8.4years, EDSS 1.0±1.2; 93% women]. Baseline, one and two year MRI was applied to an SPM12 pipeline to assess brain parenchymal fraction (BPF) and cortical GM fraction (cGMF). T2 lesion volume (T2LV) and gadolinium-enhancing lesions were assessed. Change was modeled using a mixed effects linear regression with a random intercept and fixed effects for time, group, and the time-by-group interaction. The group slope difference was assessed using the interaction term. ResultsOver two years, cGMF remained stable in the fingolimod group (p>0.05), but decreased in the untreated group (p<0.001) (group difference p<0.001). BPF change did not differ between groups (all time-points p>0.05). T2LV increased over two years in the untreated group (p<0.001) but not in the fingolimod group (p≥0.44) (group difference p<0.001). ConclusionThese results suggest a treatment effect of fingolimod on cerebral GM atrophy in the first two years. GM atrophy is more sensitive to such effects than whole brain atrophy. However, due to the non-randomized, retrospective design, heterogeneous between-group characteristics, and small sample size, these results require confirmation in future studies.