Ganglia Volumes Research Articles

Effect of Physical Training on the Morphology of Parasympathetic Atrial Ganglia after Unilateral Vagotomy in Rats.

Cardiac denervation is a serious problem in a number of patients, including patients after heart transplantation. The status of the parasympathetic ganglia after crossing the preganglionic fibers of the vagus nerve has not been enough studied. The aim of our study was to assess the effect of physical training on the morphological parameters of the parasympathetic atrial ganglia and autonomic regulation of heart rate after right- and left-sided vagotomy in rats. Morphometric characteristics of the right atrial ganglia were evaluated using an immunohistochemical method after a study that included a three-time assessment of heart rate variability. It was found that right-sided vagotomy leads to both an increase in the volume of ganglion and autonomic dysfunction. No significant change in the number of nerve cells was found in animals with false and left-sided vagotomy while maintaining preganglionic innervation after the physical training, whereas exercises led to a decrease in the volume of nerve tissue of rats with right-sided denervation. It was also found that in animals with preserved vagal innervation, the volume of atrial ganglion tissue correlates with overall heart rate variability and a normalized parasympathetic component. Therefore, a positive effect from regular physical activity on parasympathetic regulation can be expected only if preganglionic vagal influence is preserved.

The relationship between metabolic control and basal ganglia morphometry and function in individuals with early-treated phenylketonuria.

Abnormalities of the cortical white matter are the most prominent and widely-reported neurological findings in individuals with early-treated phenylketonuria (ETPKU). Much less is known regarding the effects of ETPKU on gray matter structures in the brain such as the basal ganglia. Previous findings on basal ganglia in ETPKU have been mixed. The current study was designed to further elucidate the effects of ETPKU and elevated phe levels on the morphometry of basal ganglia structures (i.e., putamen, caudate nucleus, nucleus accumbens, and globus pallidus). High resolution magnetic resonance imaging (MRI) data was collected from a sample of 37 adults with ETPKU and a demographically-matched comparison group of 33 individuals without PKU. No overall group differences (ETPKU vs. non-PKU) in basal ganglia volumes were observed. However, within the ETPKU group, poorer metabolic control (as reflected by higher blood phenylalanine levels) was associated with larger putamen volume. Vertex-wise shape analysis revealed that the volume increase was accompanied by shape changes in the middle left putamen. Consistent with this area's role in motor control, a significant correlation between left putamen volume and motor performance was also observed. Additional research is needed to fully understand the cellular level processes underlying this effect as well as to better understand the clinical impact of these morphometric changes and their potential relation to treatment response.

Obesity is associated with greater cognitive function in patients with type 2 diabetes mellitus.

The impact of obesity on cognitive function in patients with type 2 diabetes mellitus (T2DM) remains controversial. This study aimed to evaluate whether obesity, assessed by body mass index (BMI) was associated with cognitive function among T2DM patients and whether the effect of obesity on cognitive function was through brain structure. This was a post-hoc analysis of the Action to Control Cardiovascular Risk in Diabetes-Memory in Diabetes (ACCORD-MIND) study. The cognitive test battery included the Digit Symbol Substitution Test (DSST), Mini-Mental State Exam (MMSE), Rey Auditory Verbal Learning Test (RAVLT), and STROOP test, which were administered at baseline, and at 20, 40, and 80 months. A subgroup (n = 614) of the ACCORD-MIND study underwent MRI scanning at baseline and at 40 and 80 months. The total brain volume (TBV), abnormal white matter volume (AWM), abnormal gray matter volume (AGM), and abnormal basal ganglia volume (ABG) were estimated. The outcomes of this study were cognitive function and brain structure. In the adjusted analyses, BMI was positively associated with the MMSE (β:0.08, 95%CI,0.01-0.16, per standard deviation [SD] increase) and RAVLT scores (β:0.09, 95%CI,0.01-0.18). It was also associated with a greater TBV (β:7.48, 95%CI,0.29-14.67). BMI was not associated with the DSST or STROOP scores, and AWM, AGM, ABG. Mediation analysis found that the effect of BMI on MMSE/RAVLT was mediated through TBV. Obesity may be associated with greater cognitive function and the effect of BMI on cognitive function may be mediated by TBV among patients with T2DM. http://www.clinicaltrials.gov, identifier NCT00000620.

Controversial Role of Folic Acid on Diabetic Auditory Neuropathy.

Diabetic auditory neuropathy (DAN) is a common complication of diabetes that seriously affects the quality of life in patients. In this study, we investigate the role of folic acid in the treatment of DAN in an experimental rat model. Thirty-two Sprague-Dawley rats were equally divided into four groups: group 1, normal; group 2, diabetic rats; and groups 3 and 4, diabetic rats treated with folic acid (40 and 80 mg/kg, respectively). We used some tools to investigate the therapeutic effect of folic acid on DAN. We evaluated auditory brain stem response (ABR), estimated the volume and number of spiral ganglion and the volume of stria vascularis and spiral ligament by the stereological method, and measured the blood levels of homocysteine (HCY), malondialdehyde (MDA), and superoxide dismutase (SOD). Our study showed that folic acid treatment was not significantly effective in improving structural and functional disorders in DAN, even though its effectiveness in reducing HCY (P < 0.001) and MDA (P < 0.05) as oxidative biomarkers was significant. Folic acid is not effective in relieving morphological and functional disorders in DAN.

A Stereological Study of the Three Types of Ganglia of Male, Female, and Undifferentiated Scrobicularia plana (Bivalvia).

Simple SummaryIn bivalves, neurotransmitters from neural ganglia modulate gonadal maturation, and the gonadal derived sex-steroids may influence the central nervous system. However, it is unknown whether the ganglia microanatomy varies between sexes or with maturation status, besides the intrinsic differences between ganglia types. Therefore, we conducted a quantitative microscopical study on the ganglia of adult peppery furrow shell. Females show a larger glia-to-neuron numerical ratio. Further, females have a greater ganglionic volume than undifferentiated adults, with males showing intermediate values. These facts indicate that ganglia size is related somehow to maturation. Cell size seems to be the basis of the differences. The three ganglion types differ in total volumes and the volume ratio of the cortex versus the medulla. The pedal and visceral ganglia have more voluminous cortexes and medullae, but more neuronal and non-neuronal cells only in the visceral. The mean number of neural cells ranges from 12,000 to over 68,000. The new data make us wonder about the intricate and integrative neural networks of bivalves and how they relate to unsolved issues, such as nociception. The data should help interpret water pollutants’ impacts on the bivalve nervous system, whereas warning that experimental planning should consider sex and gonadal maturation.Neurotransmitters modulate gonadal maturation in bivalves. However, it remains unclear whether there are differences in the nervous system structure between sexes, maturation, and ganglia. Therefore, a stereological study was conducted on the ganglia of adult peppery furrow shell (Scrobicularia plana). Equal-sized males, females, and undifferentiated (gamete absence) animals were fixed with 10% formalin and processed for light microscopy. They were serially cut into 35 µm paraffin thick sections and stained with hematoxylin-eosin. Sections with cerebral (cerebropleural), pedal, and visceral ganglia were studied. The parameters estimated were the volumes of the ganglia, the total and relative volumes of their cortex (outer layer) and medulla (neuropil), and the total number of cells (neurons, glia, and pigmented) per ganglia and compartment. The volumes and numbers were estimated, respectively, by the Cavalieri principle and by the optical fractionator. Females show a larger glia to neuron numerical ratio. Further, females have a greater ganglionic volume than undifferentiated adults, with males showing intermediate values. These facts indicate that the ganglia size is related somehow to maturation. The cell size forms the basis of the differences because total cellularity is equal among the groups. The three ganglion types differ in total volumes and the volume ratio of the cortex versus the medulla. The greater volumes of the pedal ganglia (vis-a-vis the cerebral ones) and of the visceral ganglia (in relation to all others) imply more voluminous cortexes and medullae, but more neuronal and non-neuronal cells only in the visceral. The new fundamental data can help interpret bivalve neurophysiology.

Quantitative susceptibility mapping of basal ganglia iron is associated with cognitive and motor functions that distinguish spinocerebellar ataxia type 6 and type 3.

In spinocerebellar ataxia type 3 (SCA3), volume loss has been reported in the basal ganglia, an iron-rich brain region, but iron content has not been examined. Recent studies have reported that patients with SCA6 have markedly decreased iron content in the cerebellar dentate, coupled with severe volume loss. Changing brain iron levels can disrupt cognitive and motor functions, yet this has not been examined in the SCAs, a disease in which iron-rich regions are affected. In the present study, we used quantitative susceptibility mapping (QSM) to measure tissue magnetic susceptibility (indicating iron concentration), structural volume, and normalized susceptibility mass (indicating iron content) in the cerebellar dentate and basal ganglia in people with SCA3 (n = 10) and SCA6 (n = 6) and healthy controls (n = 9). Data were acquired using a 7T Philips MRI scanner. Supplemental measures assessed motor, cognitive, and mood domains. Putamen volume was lower in both SCA groups relative to controls, replicating prior findings. Dentate susceptibility mass and volume in SCA6 was lower than in SCA3 or controls, also replicating prior findings. The novel finding was that higher basal ganglia susceptibility mass in SCA6 correlated with lower cognitive performance and greater motor impairment, an association that was not observed in SCA3. Cerebellar dentate susceptibility mass, however, had the opposite relationship with cognition and motor function in SCA6, suggesting that, as dentate iron is depleted, it relocated to the basal ganglia, which contributed to cognitive and motor decline. By contrast, basal ganglia volume loss, rather than iron content, appeared to drive changes in motor function in SCA3. The associations of higher basal ganglia iron with lower motor and cognitive function in SCA6 but not in SCA3 suggest the potential for using brain iron deposition profiles beyond the cerebellar dentate to assess disease states within the cerebellar ataxias. Moreover, the role of the basal ganglia deserves greater attention as a contributor to pathologic and phenotypic changes associated with SCA.

Dorsal Root Ganglia Volume-Normative Values, Correlation with Demographic Determinants and Reliability of Three Different Methods of Volumetry.

Background: Dorsal root ganglia (DRG) volume assessment by MR-Neurography (MRN) has evolved to an important imaging marker in the diagnostic workup of various peripheral neuropathies and pain syndromes. The aim of this study was (1) to assess normal values of DRG volume and correlations with demographic determinants and (2) to quantify the inter-reader and inter-method reliability of three different methods of DRG volumetry. Methods: Sixty healthy subjects (mean age: 59.1, range 23–79) were examined using a 3D T2-weighted MRN of the lumbosacral plexus at 3 Tesla. Normal values of DRG L3 to S2 were obtained after exact volumetry based on manual 3D segmentation and correlations with demographic variables were assessed. For the assessment of inter-reader and inter-method reliability, DRG volumes in a subset of 25 participants were measured by two independent readers, each applying (1) exact volumetry based on 3D segmentation, (2) axis-corrected, and (3) non-axis-corrected volume estimation. Intraclass correlation coefficients were reported and the Bland–Altman analysis was conducted. Results: Mean DRG volumes ranged from 124.8 mm3 for L3 to 323.3 mm3 for S1 and did not differ between right and left DRG. DRG volume (mean of L3 to S1) correlated with body height (r = 0.42; p = 0.0008) and weight (r = 0.34; p = 0.0087). DRG of men were larger than of women (p = 0.0002); however, no difference remained after correction for body height. Inter-reader reliability was high for all three methods but best for exact volumetry (ICC = 0.99). While axis-corrected estimation was not associated with a relevant bias, non-axis-corrected estimation systematically overestimated DRG volume by on average of 15.55 mm3 (reader 1) or 18.00 mm3 (reader 2) when compared with exact volumetry. Conclusion: The here presented normal values of lumbosacral DRG volume and the correlations with height and weight may be considered in future disease specific studies and possible clinical applications. Exact volumetry was most reliable and should be considered the gold standard. However, the reliability of axis-corrected and non-axis-corrected volume estimation was also high and might still be sufficient, depending on the degree of the required measurement accuracy.

Retinal ganglion cell layer thickness and volume measured by OCT changes with age, sex, and axial length in a healthy population

BackgroundThe ganglion cell layer (GCL) measurements with Optical Coherence Tomography (OCT) are important for both ophthalmologists and neurologists because of their association with many ophthalmic and neurological diseases. Different factors can affect these measurements, such as brain pathologies, ocular axial length (AL) as well as age and sex. Studies conducted to measure the GCL have overlooked many of these factors. The purpose of this study is to examine the effect of age, sex, and AL on normal retinal GCL thickness and volume in a healthy population without any neurological diseases.MethodsA prospective cross-sectional study was designed to measure GCL thickness and total volume with OCT with automated segmentation and manual correction where needed. Visual acuity, AL, and autorefraction were also measured. A mixed linear model was used to determine the association of the effect of the various parameters on the GCL thickness and volume.ResultsOne hundred and sixteen eyes of 60 subjects (12–76 years of age, 55% female) were examined of which 77% had 0 ± 2 D of spherical equivalent, and mean axial length was 23.86 mm. About 25% of the OCT-automated GCL measurements required manual correction. GCL thickness did not differ in similar anatomic regions in right and left eyes (P > 0.05). GCL volume was greater in males relative to females after adjustment for age and axial length (1.13 ± 0.07 mm3 for males vs 1.09 ± 0.09 mm3 for females; P = 0.031). GCL thickness differed between males and females in the inner retinal ring (P = 0.025) but not in the outer ring (P = 0.66). GCL volume declined with age (P = 0.031) but not after adjustment for sex and axial length (P = 0.138). GCL volume declined with longer axial length after adjustment for age and sex (P = 0.048).ConclusionAge, sex and axial length should be taken into consideration when measuring the GCL thickness and volume with OCT. Automated OCT segmentation should be reviewed for manual adjustments.

Brain Iron and Mental Health Symptoms in Youth with and without Prenatal Alcohol Exposure.

Prenatal alcohol exposure (PAE) negatively affects brain development and increases the risk of poor mental health. We investigated if brain volumes or magnetic susceptibility, an indirect measure of brain iron, were associated with internalizing or externalizing symptoms in youth with and without PAE. T1-weighted and quantitative susceptibility mapping (QSM) MRI scans were collected for 19 PAE and 40 unexposed participants aged 7.5–15 years. Magnetic susceptibility and volume of basal ganglia and limbic structures were extracted using FreeSurfer. Internalizing and Externalizing Problems were assessed using the Behavioural Assessment System for Children (BASC-2-PRS). Susceptibility in the nucleus accumbens was negatively associated with Internalizing Problems, while amygdala susceptibility was positively associated with Internalizing Problems across groups. PAE moderated the relationship between thalamus susceptibility and internalizing symptoms as well as the relationship between putamen susceptibility and externalizing symptoms. Brain volume was not related to internalizing or externalizing symptoms. These findings highlight that brain iron is related to internalizing and externalizing symptoms differently in some brain regions for youth with and without PAE. Atypical iron levels (high or low) may indicate mental health issues across individuals, and iron in the thalamus may be particularly important for behavior in individuals with PAE.

Procedural learning and retention relative to explicit learning and retention in mild cognitive impairment and Alzheimer’s disease using a modification of the trail making test

ABSTRACT Amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD) dementia are characterized by pathological changes to the medial temporal lobes, resulting in explicit learning and retention reductions. Studies demonstrate that implicit/procedural memory processes are relatively intact in these populations, supporting different anatomical substrates for differing memory systems. This study examined differences between explicit and procedural learning and retention in individuals with aMCI and AD dementia relative to matched healthy controls. We also examined anatomical substrates using volumetric MRI. Results revealed expected difficulties with explicit learning and retention in individuals with aMCI and AD with relatively preserved procedural memory. Explicit verbal retention was associated with medial temporal cortex volumes. However, procedural retention was not related to medial temporal or basal ganglia volumes. Overall, this study confirms the dissociation between explicit relative to procedural learning and retention in aMCI and AD dementia and supports differing anatomical substrates.

Higher limbic and basal ganglia volumes in surviving COVID-negative patients and the relations to fatigue

BackgroundAmong systemic abnormalities caused by the novel coronavirus, little is known about the critical attack on the central nervous system (CNS). Few studies have shown cerebrovascular pathologies that indicate CNS involvement in acute patients. However, replication studies are necessary to verify if these effects persist in COVID-19 survivors more conclusively. Furthermore, recent studies indicate fatigue is highly prevalent among ‘long-COVID’ patients. How morphometry in each group relate to work-related fatigue need to be investigated. MethodCOVID survivors were MRI scanned two weeks after hospital discharge. We hypothesized, these survivors will demonstrate altered gray matter volume (GMV) and experience higher fatigue levels when compared to healthy controls, leading to stronger correlation of GMV with fatigue. Voxel-based morphometry was performed on T1-weighted MRI images between 46 survivors and 30 controls. Unpaired two-sample t-test and multiple linear regression were performed to observe group differences and correlation of fatigue with GMV. ResultsThe COVID group experienced significantly higher fatigue levels and GMV of this group was significantly higher within the Limbic System and Basal Ganglia when compared to healthy controls. Moreover, while a significant positive correlation was observed across the whole group between GMV and self-reported fatigue, COVID subjects showed stronger effects within the Posterior Cingulate, Precuneus and Superior Parietal Lobule. ConclusionBrain regions with GMV alterations in our analysis align with both single case acute patient reports and current group level neuroimaging findings. We also newly report a stronger positive correlation of GMV with fatigue among COVID survivors within brain regions associated with fatigue, indicating a link between structural abnormality and brain function in this cohort.

Dorsal Root Ganglion Volumetry by MR Gangliography.

Dorsal root ganglion MR imaging (MR gangliography) is increasingly gaining clinical-scientific relevance. However, dorsal root ganglion morphometry by MR imaging is typically performed under the assumption of ellipsoid geometry, which remains to be validated. Sixty-four healthy volunteers (37 [57.8%] men; mean age, 31.5 [SD, 8.3] years) underwent MR gangliography of the bilateral L4-S2 levels (3D-T2WI TSE spectral attenuated inversion recovery-sampling perfection with application-optimized contrasts by using different flip angle evolution, isotropic voxels = 1.1 mm³, TE = 301 ms). Ground truth dorsal root ganglion volumes were bilaterally determined for 96 dorsal root ganglia (derivation cohort) by expert manual 3D segmentation by 3 independent raters. These ground truth dorsal root ganglion volumes were then compared with geometric ellipsoid dorsal root ganglion approximations as commonly practiced for dorsal root ganglion morphometry. On the basis of the deviations from ellipsoid geometry, improved volume estimation could be derived and was finally applied to a large human validation cohort (510 dorsal root ganglia). Commonly used equations of ellipsoid geometry underestimate true dorsal root ganglion volume by large degrees (factor = 0.42-0.63). Ground truth segmentation enabled substantially optimizing dorsal root ganglion geometric approximation using its principal axes lengths by deriving the dorsal root ganglion volume term of [Formula: see text]. Using this optimization, the mean volumes of 510 lumbosacral healthy dorsal root ganglia were as follows: L4: 211.3 (SD, 52.5) mm³, L5: 290.7 (SD, 90.9) mm³, S1: 384.2 (SD, 145.0) mm³, and S2: 192.4 (SD, 52.6) mm³. Dorsal root ganglion volume increased from L4 to S1 and decreased from S1 to S2 (P < .001). Dorsal root ganglion volume correlated with subject height (r = . 22, P < .001) and was higher in men (P < .001). Dorsal root ganglion volumetry by measuring its principal geometric axes on MR gangliography can be substantially optimized. By means of this optimization, dorsal root ganglion volume distribution was estimated in a large healthy cohort for the clinically most relevant lumbosacral levels, L4-S2.

Retinal nerve fiber and ganglion cell complex layer thicknesses mirror brain atrophy in patients with relapsing-remitting multiple sclerosis.

Multiple sclerosis (MS) is associated with progressive brain atrophy, which in turn correlates with disability, depression, and cognitive impairment. Relapsing-remitting multiple sclerosis (RRMS) is a type of MS in which relapses of the disease are followed by remission periods. This is the most common type of the disease. There is a significant need for easy and low-cost methods to these cerebral changes. Changes in retinal layer thickness may reflect alterations in brain white and gray matter volumes. Therefore, this paper aims to determine whether retinal layer thickness, measured using optical coherence tomography (OCT), correlates with volumetric brain assessments obtained by magnetic resonance imaging (MRI). This retrospective cohort study recruited 53 patients with relapsing-remitting MS who underwent MRI and OCT examinations for evaluation of brain compartment volumes and thickness of retinal layers, respectively. OCT parameters, including central retinal thickness; retinal nerve fiber layer thickness (RNFL, peripapillary thickness); ganglion cell complex thickness (GCC, macular thickness); and Expanded Disability Status Scale (EDSS) results were compared with MRI parameters (cerebral cortex; cerebral cortex and basal ganglia combined; brain hemispheres without the ventricular system; and white matter plaques). We also checked whether there is a correlation between the number of RRMS and OCT parameters. Our primary objective was to identify whether these patients had retinal thickness changes, and our secondary objective was to check if those changes correlated with the MRI brain anatomical changes. RNFL and GCC thicknesses were strongly (p-value < 0.05) associated with (i) cerebral cortex volume, (ii) combination of brain cortex and basal ganglia volumes, and (iii) the hemispheres but without the ventricular system. White matter plaques (combined) showed only weak or no correlation with RNFL and GCC. There was no correlation between central retinal thickness and brain compartment volumes, and there were weak or no correlations between the summary EDSS scores and OCT results. Retinal layer thickness measured by OCT correlates with select volumetric brain assessments on MRI. During the course of RRMS, the anatomo-pathological structure of the retina might serve as a surrogate marker of brain atrophy and clinical progression within selected domains.

Medial temporal lobe and basal ganglia volume trajectories in persistent negative symptoms following a first episode of psychosis

BackgroundPersistent negative symptoms (PNS, e.g., avolition, anhedonia, alogia) are present in up to 30% of individuals diagnosed with a first episode of psychosis and greatly impact functional outcomes. PNS and secondary PNS (sPNS: concomitant with positive, depressive, or extrapyramidal symptoms) may index distinct pathophysiologies reflected by structural brain changes, particularly in the medial temporal lobe (MTL) and basal ganglia. AimsWe sought to characterize dynamic brain changes related to PNS over the course of 2 years following a first episode of psychosis. MethodLongitudinal volumetric trajectories within the MTL (hippocampus, parahippocampal gyrus, entorhinal cortex, perirhinal cortex) and basal ganglia (caudate, putamen, pallidum) were investigated in 98 patients with first-episode psychosis and 86 healthy controls using generalized estimating equations. ResultsIn left hippocampus, PNS (n = 25 at baseline) showed decreased volumes over time, sPNS (n = 26) volumes remained stable, and non-PNS (n = 47) volumes increased over time to control levels. PNS-specific changes were observed in left hippocampus and left perirhinal cortex, with the greatest decline from 12 to 24 months to levels significantly below those of non-PNS and controls. Affective/non-affective diagnosis, antipsychotic medication dosage and adherence at baseline did not significantly impact these findings. Basal ganglia volume trajectories did not distinguish between PNS and sPNS. ConclusionsThe current study highlights distinct structural brain trajectories in PNS that are prominent in the left MTL. Basal ganglia alterations may contribute to PNS irrespective of their etiology. Left MTL volume reductions were most evident after 1 year of treatment, highlighting the importance of targeted early interventions.

Characterization of basal ganglia volume changes in the context of HIV and polysubstance use

HIV and psychoactive substances can impact the integrity of the basal ganglia (BG), a neural substrate of cognition, motor control, and reward-seeking behaviors. This study assessed BG gray matter (GM) volume as a function of polysubstance (stimulant and opioid) use and HIV status. We hypothesized that comorbid polysubstance use and HIV seropositivity would alter BG GM volume differently than would polysubstance use or HIV status alone. We collected structural MRI scans, substance use history, and HIV diagnoses. Participants who had HIV (HIV +), a history of polysubstance dependence (POLY +), both, or neither completed assessments for cognition, motor function, and risk-taking behaviors (N = 93). All three clinical groups showed a left-lateralized pattern of GM reduction in the BG relative to controls. However, in the HIV + /POLY + group, stimulant use was associated with increased GM volume within the globus pallidus and putamen. This surpassed the effects from opioid use, as indicated by decreased GM volume throughout the BG in the HIV-/POLY + group. Motor learning was impaired in all three clinical groups, and in the HIV + /POLY + group, motor learning was associated with increased caudate and putamen GM volume. We also observed associations between BG GM volume and risk-taking behaviors in the HIV + /POLY- and HIV-/POLY + groups. The effects of substance use on the BG differed as a function of substance type used, HIV seropositivity, and BG subregion. Although BG volume decreased in association with HIV and opioid use, stimulants can, inversely, lead to BG volume increases within the context of HIV.

The role of cerebellar damage in explaining disability and cognition in multiple sclerosis phenotypes: a multiparametric MRI study.

Cerebellar involvement is not comprehensively studied from an MRI point of view in multiple sclerosis (MS). We aimed to quantify cerebellar damage and identify predictors of physical disability and cognitive dysfunction in MS patients, and to characterize patients with cerebellar disability. In this prospective study, 164 (89 relapsing-remitting and 75 progressive) MS patients and 53 healthy controls were enrolled. Subjects underwent 3T MRI with sequences for assessing lesions and atrophy in cerebellum, supratentorial brain, brainstem and cervical cord. Cerebellar peduncle diffusion-tensor metrics were also derived. Random forest models identified MRI predictors of Expanded Disability Status Scale (EDSS) score and cognition z-score. Hierarchical clustering was applied on MRI metrics in patients with cerebellar disability. In MS patients, predictors of higher EDSS score (out-of-bag-R2 = 0.83) were: lower cord grey matter (GM) and global areas, brain volume, GM volume (GMV), cortical GMV, cerebellum lobules I-IV and vermis GMV; and higher cord GM and brainstem lesion volume (LV). Predictors of lower cognition z-score (out-of-bag-R2 = 0.25) were: higher supratentorial and superior cerebellar peduncle LV; and lower brain, thalamus and basal ganglia volumes, GMV, cerebellum lobule VIIIb and Crus II GMV. In patients with cerebellar disability, we found three clusters with homogenous MRI metrics: patients with high brain lesion volumes (including cerebellar peduncles), those with marked cerebellum GM atrophy and patients with severe cord damage. Damage to cerebellum GM and connecting structures has a relevant role in explaining cognitive dysfunction and physical disability in MS. Data-driven MRI clustering might improve our knowledge of MRI-clinical correlations.

Structural Basal Ganglia Correlates of Subjective Fatigue in Middle-Aged and Older Adults.

Fatigue is among the most common complaints in community-dwelling older adults, yet its etiology is poorly understood. Based on models implicating frontostriatal pathways in fatigue pathogenesis, we hypothesized that smaller basal ganglia volume would be associated with higher levels of subjective fatigue and reduced set-shifting in middle-aged and older adults without dementia or other neurologic conditions. Forty-eight non-demented middle-aged and older adults (Mage = 68.1, SD = 9.4; MMMSE = 27.3, SD = 1.9) completed the Fatigue Symptom Inventory, set-shifting measures, and structural MRI as part of a clinical evaluation for subjective cognitive complaints. Associations were examined cross-sectionally. Linear regression analyses showed that smaller normalized basal ganglia volumes were associated with more severe fatigue (β = -.29, P = .041) and poorer Trail Making Test B-A (TMT B-A) performance (β = .30, P = .033) controlling for depression, sleep quality, vascular risk factors, and global cognitive status. Putamen emerged as a key structure linked with both fatigue (r = -.43, P = .003) and TMT B-A (β = .35, P = .021). The link between total basal ganglia volume and reduced TMT B-A was particularly strong in clinically fatigued patients. This study is among the first to show that reduced basal ganglia volume is an important neurostructural correlate of subjective fatigue in physically able middle-aged and older adults without neurological conditions. Findings suggest that fatigue and rapid set-shifting deficits may share common neural underpinnings involving the basal ganglia, and provide a framework for studying the neuropathogenesis and treatment of subjective fatigue.

Linking Vestibular Function and Subcortical Gray Matter Volume Changes in a Longitudinal Study of Aging Adults

Emerging evidence suggests a relationship between impairments of the vestibular (inner ear balance) system and alterations in the function and the structure of the central nervous system (CNS) in older adults. However, it is unclear whether age-related vestibular loss is associated with volume loss in brain regions known to receive vestibular input. To address this gap, we investigated the association between vestibular function and the volumes of four structures that process vestibular information (the hippocampus, entorhinal cortex, thalamus, and basal ganglia) in a longitudinal study of 97 healthy, older participants from the Baltimore Longitudinal Study of Aging. Vestibular testing included cervical vestibular-evoked myogenic potentials (cVEMP) to measure saccular function, ocular VEMP (oVEMP) to measure utricular function, and video head impulse tests to measure the horizontal semicircular canal vestibulo-ocular reflex (VOR). Participants in the sample had vestibular and brain MRI data for a total of one (18.6%), two (49.5%), and three (32.0%) visits. Linear mixed-effects regression was used to model regional volume over time as a function of vestibular physiological function, correcting for age, sex, intracranial volume, and intersubject random variation in the baseline levels and rates of change of volume over time. We found that poorer saccular function, characterized by lower cVEMP amplitude, is associated with reduced bilateral volumes of the basal ganglia and thalamus at each time point, demonstrated by a 0.0714 cm3 ± 0.0344 (unadjusted p = 0.038; 95% CI: 0.00397–0.139) lower bilateral-mean volume of the basal ganglia and a 0.0440 cm3 ± 0.0221 (unadjusted p = 0.046; 95% CI: 0.000727–0.0873) lower bilateral-mean volume of the thalamus for each 1-unit lower cVEMP amplitude. We also found a relationship between a lower mean VOR gain and lower left hippocampal volume (β = 0.121, unadjusted p = 0.018, 95% CI: 0.0212–0.222). There were no significant associations between volume and oVEMP. These findings provide insight into the specific brain structures that undergo atrophy in the context of age-related loss of peripheral vestibular function.

Bihemispheric developmental alterations in basal ganglia volumes following unilateral perinatal stroke

IntroductionPerinatal stroke affects millions of children and results in lifelong disability. Two forms prevail: arterial ischemic stroke (AIS), and periventricular venous infarction (PVI). With such focal damage early in life, neural structures may reorganize during development to determine clinical function, particularly in the contralesional hemisphere. Such processes are increasingly understood in the motor system, however, the role of the basal ganglia, a group of subcortical nuclei that are critical to movement, behaviour, and learning, remain relatively unexplored. Perinatal strokes that directly damage the basal ganglia have been associated with worse motor outcomes, but how developmental plasticity affects bilateral basal ganglia structure is unknown. We hypothesized that children with perinatal stroke have alterations in bilateral basal ganglia volumes, the degree of which correlates with clinical motor function. MethodsChildren with AIS or PVI, and controls, aged 6–19 years, were recruited from a population-based cohort. MRIs were acquired on a 3 T GE MR750w scanner. High-resolution T1-weighted images (166 slices, 1 mm isotropic voxels) underwent manual segmentations of bilateral caudate and putamen. Extracted volumes were corrected for total intracranial volume. A structure volume ratio quantified hemispheric asymmetry of caudate and putamen (non-dominant/dominant hemisphere structure volume) with ratios closer to 1 reflecting a greater degree of symmetry between structures. Participants were additionally dichotomized by volume ratios into two groups, those with values above the group mean (0.8) and those below. Motor function was assessed using the Assisting Hand Assessment (AHA) and the Box and Blocks test in affected (BBTA) and unaffected (BBTU) hands. Group differences in volumes were explored using Kruskal-Wallis tests, and interhemispheric differences using Wilcoxon. Partial Spearman correlations explored associations between volumes and motor function (factoring out age, and whole-brain white matter volume, a proxy for lesion extent). ResultsIn the dominant (non-lesioned) hemisphere, volumes were larger in AIS compared to PVI for both the caudate (p < 0.05) and putamen (p < 0.01) but comparable between stroke groups and controls. Non-dominant (lesioned) hemisphere volumes were larger for controls than AIS for the putamen (p < 0.05), and for the caudate in PVI (p = 0.001). Interhemispheric differences showed greater dominant hemisphere volumes for the putamen in controls (p < 0.01), for both the caudate (p < 0.01) and putamen (p < 0.001) in AIS, and for the caudate (p = 0.01) in PVI. Motor scores did not differ between AIS and PVI thus groups were combined to increase statistical power. Better motor scores were associated with larger non-dominant putamen volumes (BBTA: r = 0.40, p = 0.011), and larger putamen volume ratios (BBTA: r = 0.52, p < 0.001, AHA: r = 0.43, p < 0.01). For those with relatively symmetrical putamen volume ratios (ratio > group mean of 0.8), age was positively correlated with BBTA (r = 0.54, p < 0.01) and BBTU (r = 0.69, p < 0.001). For those with more asymmetrical putamen volume ratios, associations with motor function and age were not seen (BBTA: r = 0.21, p = 0.40, BBTU: r = 0.37, p = 0.13). ConclusionSpecific perinatal stroke lesions affect different elements of basal ganglia development. PVI primarily affected the caudate, while AIS primarily affected the putamen. Putamen volumes in the lesioned hemisphere are associated with clinical motor function. The basal ganglia should be included in evolving models of developmental plasticity after perinatal stroke.

Iron deficiency and internalizing symptom severity in unmedicated adolescents: a pilot study.

Iron plays a key role in a broad set of metabolic processes. Iron deficiency is the most common nutritional deficiency in the world, but its neuropsychiatric implications in adolescents have not been examined. Twelve- to 17-year-old unmedicated females with major depressive or anxiety disorders or with no psychopathology underwent a comprehensive psychiatric assessment for this pilot study. A T1-weighted magnetic resonance imaging scan was obtained, segmented using Freesurfer. Serum ferritin concentration (sF) was measured. Correlational analyses examined the association between body iron stores, psychiatric symptom severity, and basal ganglia volumes, accounting for confounding variables. Forty females were enrolled, 73% having a major depressive and/or anxiety disorder, 35% with sF < 15 ng/mL, and 50% with sF < 20 ng/mL. Serum ferritin was inversely correlated with both anxiety and depressive symptom severity (r = -0.34, p < 0.04 and r = -0.30, p < 0.06, respectively). Participants with sF < 15 ng/mL exhibited more severe depressive and anxiety symptoms as did those with sF < 20 ng/mL. Moreover, after adjusting for age and total intracranial volume, sF was inversely associated with left caudate (Spearman's r = -0.46, p < 0.04), left putamen (r = -0.58, p < 0.005), and right putamen (r = -0.53, p < 0.01) volume. Brain iron may become depleted at a sF concentration higher than the established threshold to diagnose iron deficiency (i.e. 15 ng/mL), potentially disrupting brain maturation and contributing to the emergence of internalizing disorders in adolescents.