Subcortical Gray Matter Research Articles

Examining the structural correlates of amyloid‐beta in people with DLB

AbstractBackgroundDementia with Lewy bodies (DLB) is a neurodegenerative disorder characterized pathologically by the deposition of alpha synuclein. Many patients with DLB also have brain compatible with Alzheimer’s disease (namely Amyloid‐β and tau), which can lead to challenges with clinical diagnosis and management. In this study we aim to understand the influence of Aβ on brain atrophy in DLB patients.Method19 participants with probable DLB underwent 3T MRI T1‐weighted (voxel size=0.8x0.8x0.8mm3, TR=2400ms, TE=2.31ms) and β‐amyloid (Aβ) PET (radiotracer 18F‐NAV4694) imaging. Participants were grouped into Aβ negative (n=10; age=71.6±5.8 years) and Aβ positive (n=9; age=75.1±4.3 years) with a threshold of 50 centiloid units to identify neuropathological change (Amadoru et al. 2020). Brain volume measures (regional subcortical grey matter and global white and grey matter) were segmented from T1‐weighted images with FreeSurfer (Fischl et al. 2002, Fischl 2012). Given previous literature suggesting prominence of thalamic structural changes in DLB, we also specifically analysed changes in the thalamus by segmenting the thalamus into 25 nuclei, which were then grouped into six regions (anterior, lateral, ventral, intralaminar, medial and posterior) (Watson et al. 2017, Iglesias et al. 2018). All brain volumes were expressed as fractions of intracranial volume to account for differences in head size. Group comparison analyses were not controlled for age and sex as both these covariates did not statistically differ between groups.ResultBrain volume differed significantly between Aβ‐ and Aβ+ DLB patients in the left thalamus (Aβ‐:4.39±0.37x103, Aβ+:4.07±0.19x103, p=0.03) and right thalamus (Aβ‐:4.17±0.34x103, Aβ+:3.84±0.22 x103, p=0.03). Specifically, the ventral (LEFT; Aβ‐:1.78±0.15, Aβ+:1.63±0.14, p=0.03. RIGHT; Aβ‐:1.83±0.15, Aβ+:1.65±0.12, p=0.01) and posterior (LEFT; Aβ‐:1.30±0.12, Aβ+:1.17±0.10, p=0.04. RIGHT; Aβ‐:1.42±0.14, Aβ+:1.21±0.12, p=0.003) regions were significantly reduced in Aβ+ compared to Aβ‐ DLB patients.ConclusionWe demonstrated significant thalamic atrophy in Aβ+ patients compared to Aβ‐ DLB patients. We did not observe significant differences in grey matter and hippocampal volume between patient groups. This study showed that AD‐related processes in DLB patients are associated with thalamic atrophy, specifically in the ventral and posterior regions. Future studies would benefit a larger DLB cohort to further understand the association between AD‐related pathology and the regional thalamic correlates of clinical function.

Age‐related ventricular expansion is not spatially concordant with MR‐visible periventricular white matter disease

AbstractBackgroundVentricular expansion (VE) is recognized as one of the earliest predictors of Alzheimer’s disease (AD); however, VE is also ubiquitous in normal aging. VE is reportedly caused by an ex vacuo mechanism, whereby tissue that appears as periventricular white matter hyperintensity visible on FLAIR MRI (PVH) experiences white matter (WM) atrophy and is subsumed by the lateral ventricles. This longitudinal study sought to test the degree to which the locations into which the ventricles expand were previously PVH as opposed to other tissues.MethodSixty‐five cognitively intact aged subjects each received 2‐6 T1‐weighted and FLAIR MRIs (Table 1). Each volume was rigidly coregistered to the baseline volume and gray matter (GM), lateral ventricular and PVH masks were generated for each timepoint. Ventricular growth masks (VG) were generated for each subsequent timepoint, each VG voxel was classified into either GM, PVH, or normal appearing white matter (NAWM) per overlap with previous timepoint tissue masks (Figure 1A).ResultOverall, average VE between visits was 5.1cm3. Over all subjects and visits, 4.2% of VE occurred where tissue had been previously marked as PVH, 16.1% of VE occurred where tissue had previously been marked as GM, including subcortical GM and the hippocampus, and 75.4% of VE occurred in tissue that had been previously marked as NAWM (Figure 1B).ConclusionThe results support an alternative explanation for VE; that is, that ex vacuo expansion of the lateral ventricles may not be the primary mechanism by which ventriculomegaly occurs in aging. One possible explanation is that unaltered CSF production in the face of dysfunctional CSF egress dynamics causes fluid stasis and reflux which increases pressure in the lateral ventricles.

The neurobiological basis of divergent thinking: Insight from gene co-expression network-based analysis

Although many efforts have been made to explore the genetic basis of divergent thinking (DT), there is still a gap in the understanding of how these findings relate to the neurobiology of DT. In a combined sample of 1,682 Chinese participants, by integrating GWAS with previously identified brain-specific gene co-expression network modules, this study explored for the first time the functional brain-specific gene co-expression networks underlying DT. The results showed that gene co-expression network modules in anterior cingulate cortex, caudate, amygdala and substantia nigra were enriched with DT association signals. Further functional enrichment analysis showed that these DT-related gene co-expression network modules were enriched for key biological process and cellular component related to myelination, suggesting that cortical and sub-cortical grey matter myelination may serve as important neurobiological basis of DT. Although the underlying mechanisms need to be further refined, this exploratory study may provide new insight into the neurobiology of DT.

High-resolution mapping and digital atlas of subcortical regions in the macaque monkey based on matched MAP-MRI and histology

Subcortical nuclei and other deep brain structures are known to play an important role in the regulation of the central and peripheral nervous systems. It can be difficult to identify and delineate many of these nuclei and their finer subdivisions in conventional MRI due to their small size, buried location, and often subtle contrast compared to neighboring tissue. To address this problem, we applied a multi-modal approach in ex vivo non-human primate (NHP) brain that includes high-resolution mean apparent propagator (MAP)-MRI and five different histological stains imaged with high-resolution microscopy in the brain of the same subject. By registering these high-dimensional MRI data to high-resolution histology data, we can map the location, boundaries, subdivisions, and micro-architectural features of subcortical gray matter regions in the macaque monkey brain. At high spatial resolution, diffusion MRI in general, and MAP-MRI in particular, can distinguish a large number of deep brain structures, including the larger and smaller white matter fiber tracts as well as architectonic features within various nuclei. Correlation with histology from the same brain enables a thorough validation of the structures identified with MAP-MRI. Moreover, anatomical details that are evident in images of MAP-MRI parameters are not visible in conventional T1-weighted images. We also derived subcortical template “SC21” from segmented MRI slices in three-dimensions and registered this volume to a previously published anatomical template with cortical parcellation (Reveley et al., 2017; Saleem and Logothetis, 2012), thereby integrating the 3D segmentation of both cortical and subcortical regions into the same volume. This newly updated three-dimensional D99 digital brain atlas (V2.0) is intended for use as a reference standard for macaque neuroanatomical, functional, and connectional imaging studies, involving both cortical and subcortical targets. The SC21 and D99 digital templates are available as volumes and surfaces in standard NIFTI and GIFTI formats.

Association of subcortical gray-matter volumes with life-course-persistent antisocial behavior in a population-representative longitudinal birth cohort.

Neuropsychological evidence supports the developmental taxonomy theory of antisocial behavior, suggesting that abnormal brain development distinguishes life-course-persistent from adolescence-limited antisocial behavior. Recent neuroimaging work confirmed that prospectively-measured life-course-persistent antisocial behavior is associated with differences in cortical brain structure. Whether this extends to subcortical brain structures remains uninvestigated. This study compared subcortical gray-matter volumes between 672 members of the Dunedin Study previously defined as exhibiting life-course-persistent, adolescence-limited or low-level antisocial behavior based on repeated assessments at ages 7-26 years. Gray-matter volumes of 10 subcortical structures were compared across groups. The life-course-persistent group had lower volumes of amygdala, brain stem, cerebellum, hippocampus, pallidum, thalamus, and ventral diencephalon compared to the low-antisocial group. Differences between life-course-persistent and adolescence-limited individuals were comparable in effect size to differences between life-course-persistent and low-antisocial individuals, but were not statistically significant due to less statistical power. Gray-matter volumes in adolescence-limited individuals were near the norm in this population-representative cohort and similar to volumes in low-antisocial individuals. Although this study could not establish causal links between brain volume and antisocial behavior, it constitutes new biological evidence that all people with antisocial behavior are not the same, supporting a need for greater developmental and diagnostic precision in clinical, forensic, and policy-based interventions.

Late chronotype is linked to greater cortical thickness in the left fusiform and entorhinal gyri

ABSTRACT Humans can be classified as early, intermediate and late chronotypes based on their preferred sleep and wakefulness patterns. Eveningness is associated with increased risk of developing several psychiatric conditions, such as major depressive and addictive disorders, however, the anatomical basis of chronotype distinctions, which might predispose to the above conditions, remains largely unexplored. Using magnetic resonance imaging data from 113 healthy young adults (71 females), we aimed to correlate individual chronotype scores with cortical thickness, as well as subcortical and cerebellar grey matter volume. The results revealed one cluster located in the left fusiform and entorhinal gyri showing increased cortical thickness with increasing preference for eveningness. These structures are well positioned to mediate well-established chronotype differences in affective processing, i.e. increased negative affect in late chronotypes. Furthermore, in line with the earlier findings, we found no differences in subcortical and cerebellar grey matter volume. Thus, our study confirms that circadian preference is associated with specific structural cortical substrates and provides a potential anatomical basis for differential affective functioning in morning- and evening-oriented individuals, bridging the gap between brain structure and function.

Hybrid PET-MRI for early detection of dopaminergic dysfunction and microstructural degradation involved in Parkinson\u2019s disease

Dopamine depletion and microstructural degradation underlie the neurodegenerative processes in Parkinson’s disease (PD). To explore early alterations and underlying associations of dopamine and microstructure in PD patients utilizing the hybrid positron emission tomography (PET)-magnetic resonance imaging (MRI). Twenty-five PD patients in early stages and twenty-four matched healthy controls underwent hybrid 18F-fluorodopa (DOPA) PET-diffusion tensor imaging (DTI) scanning. The striatal standardized uptake value ratio (SUVR), DTI maps (fractional anisotropy, FA; mean diffusivity, MD) in subcortical grey matter, and deterministic tractography of the nigrostriatal pathway were processed. Values in more affected (MA) side, less affected (LA) side and mean were analysed. Correlations and mediations among PET, DTI and clinical characteristics were further analysed. PD groups exhibited asymmetric pattern of dopaminergic dysfunction in putamen, impaired integrity in the microstructures (nigral FA, putaminal MD, and FA of nigrostriatal projection). On MA side, significant associations between DTI metrics (nigral FA, putaminal MD, and FA of nigrostriatal projection) and motor performance were significantly mediated by putaminal SUVR, respectively. Early asymmetric disruptions in putaminal dopamine concentrations and nigrostriatal pathway microstructure were detected using hybrid PET-MRI. The findings further implied that molecular degeneration mediates the modulation of microstructural disorganization on motor dysfunction in the early stages of PD.

The Epic of the Thalamus in Anatomical Language.

Understanding the origin of Greek and Latin words used as metaphors to label brain structures gives a unique window into how scientific and medical knowledge was produced, preserved, and transmitted through generations. The history of the term thalamus exemplifies the complex historical process that led to the current anatomical terminology. From its first mention by Galen of Pergamon in the 2nd century A.D. to its definitive and current use by Thomas Willis in 1664, the thalamus had an epical journey through 1500 years across Europe, the Middle East, and the North of Africa. The thalamus was confusingly described by Galen, in the Greek language, as a chamber to the brain ventricles. The term thalamus was transferred from Greek to Syriac through the translations of Galen’s books done in Baghdad and also from Syriac to Arabic. Then, it was translated in Europe during the Middle Ages from the Arabic versions of Galen’s books to Latin. Later, during the Early Renaissance, it was translated again to Latin directly from the Greek versions of Galen’s books. Along this epical journey through languages, the term thalamus switched from referring to a hollow structure connected to brain ventricles to naming a solid structure at the rostral end of the brainstem. Finally, the thalamus was translated from Latin to modern languages, where it is used, until today, to name a nuclear complex of subcortical gray matter in the lateral walls of the third ventricle.

Estimating the effect of a scanner upgrade on measures of grey matter structure for longitudinal designs.

Longitudinal imaging studies are crucial for advancing the understanding of brain development over the lifespan. Thus, more and more studies acquire imaging data at multiple time points or with long follow-up intervals. In these studies changes to magnetic resonance imaging (MRI) scanners often become inevitable which may decrease the reliability of the MRI assessments and introduce biases. We therefore investigated the difference between MRI scanners with subsequent versions (3 Tesla Siemens Verio vs. Skyra) on the cortical and subcortical measures of grey matter in 116 healthy, young adults using the well-established longitudinal FreeSurfer stream for T1-weighted brain images. We found excellent between-scanner reliability for cortical and subcortical measures of grey matter structure (intra-class correlation coefficient > 0.8). Yet, paired t-tests revealed statistically significant differences in at least 67% of the regions, with percent differences around 2 to 4%, depending on the outcome measure. Offline correction for gradient distortions only slightly reduced these biases. Further, T1-imaging based quality measures reflecting gray-white matter contrast systematically differed between scanners. We conclude that scanner upgrades during a longitudinal study introduce bias in measures of cortical and subcortical grey matter structure. Therefore, before upgrading a MRI scanner during an ongoing study, researchers should prepare to implement an appropriate correction method for these effects.

Tackling clinical heterogeneity across the amyotrophic lateral sclerosis–frontotemporal dementia spectrum using a transdiagnostic approach

The disease syndromes of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) display considerable clinical, genetic and pathological overlap, yet mounting evidence indicates substantial differences in progression and survival. To date, there has been limited examination of how profiles of brain atrophy might differ between clinical phenotypes. Here, we address this longstanding gap in the literature by assessing cortical and subcortical grey and white matter volumes on structural MRI in a large cohort of 209 participants. Cognitive and behavioural changes were assessed using the Addenbrooke’s Cognitive Examination and the Cambridge Behavioural Inventory. Relative to 58 controls, behavioural variant FTD (n = 58) and ALS–FTD (n = 41) patients displayed extensive atrophy of frontoinsular, cingulate, temporal and motor cortices, with marked subcortical atrophy targeting the hippocampus, amygdala, thalamus and striatum, with atrophy further extended to the brainstem, pons and cerebellum in the latter group. At the other end of the spectrum, pure-ALS patients (n = 52) displayed considerable frontoparietal atrophy, including right insular and motor cortices and pons and brainstem regions. Subcortical regions included the bilateral pallidum and putamen, but to a lesser degree than in the ALS–FTD and behavioural variant FTD groups. Across the spectrum the most affected region in all three groups was the insula, and specifically the anterior part (76–90% lower than controls). Direct comparison of the patient groups revealed disproportionate temporal atrophy and widespread subcortical involvement in ALS–FTD relative to pure-ALS. In contrast, pure-ALS displayed significantly greater parietal atrophy. Both behavioural variant FTD and ALS–FTD were characterized by volume decrease in the frontal lobes relative to pure-ALS. The motor cortex and insula emerged as differentiating structures between clinical syndromes, with bilateral motor cortex atrophy more pronounced in ALS–FTD compared with pure-ALS, and greater left motor cortex and insula atrophy relative to behavioural variant FTD. Taking a transdiagnostic approach, we found significant associations between abnormal behaviour and volume loss in a predominantly frontoinsular network involving the amygdala, striatum and thalamus. Our findings demonstrate the presence of distinct atrophy profiles across the ALS–FTD spectrum, with key structures including the motor cortex and insula. Notably, our results point to subcortical involvement in the origin of behavioural disturbances, potentially accounting for the marked phenotypic variability typically observed across the spectrum.

Structural MRI signatures of grey matter atrophy in genetic frontotemporal lobar degeneration

We aimed to assess cortical, subcortical and cerebellar grey matter (GM) atrophy using MRI in patients with disorders of the frontotemporal lobar degeneration (FTLD) spectrum with known genetic mutations.

Global hippocampal and selective thalamic nuclei atrophy differentiate chronic TBI from Non-TBI

Traumatic brain injury (TBI) may increase susceptibility to neurodegenerative diseases later in life. One neurobiological parallel between chronic TBI and neurodegeneration may be accelerated aging and the nature of atrophy across subcortical gray matter structures. The main aim of the present investigation is to evaluate and rank the degree that subcortical gray matter atrophy differentiates chronic moderate-severe TBI from non-TBI participants by evaluating morphometric differences between groups. Forty individuals with moderate-severe chronic TBI (9.23 yrs from injury) and 33 healthy controls (HC) underwent high resolution 3D T1-weighted structural magnetic resonance imaging. Whole brain volume was classified into white matter, cortical and subcortical gray matter structures with hippocampi and thalami further segmented into subfields and nuclei, respectively. Extensive atrophy was observed across nearly all brain regions for chronic TBI participants. A series of multivariate logistic regression models identified subcortical gray matter structures of the hippocampus and thalamus as the most sensitive to differentiating chronic TBI from non-TBI participants (McFadden R2 = .36, p < .001). Further analyses revealed the pattern of hippocampal atrophy to be global, occurring across nearly all subfields. The pattern of thalamic atrophy appeared to be much more selective and non-uniform, with largest between-group differences evident for nuclei bordering the ventricles. Subcortical gray matter was negatively correlated with time since injury (r = −.31, p = .054), while white matter and cortical gray matter were not. Cognitive ability was lower in the chronic TBI group (Cohen's d = .97, p = .003) and correlated with subcortical structures including the pallidum (r2 = .23, p = .038), thalamus (r2 = .36, p = .007) and ventral diencephalon (r2 = .23, p = .036). These data may support an accelerated aging hypothesis in chronic moderate-severe TBI that coincides with a similar neuropathological profile found in neurodegenerative diseases.

Structural MRI Signatures in Genetic Presentations of the Frontotemporal Dementia/Motor Neuron Disease Spectrum.

Background and ObjectivesTo assess cortical, subcortical, and cerebellar gray matter (GM) atrophy using MRI in patients with disorders of the frontotemporal lobar degeneration (FTLD) spectrum with known genetic mutations.MethodsSixty-six patients carrying FTLD-related mutations were enrolled, including 44 with pure motor neuron disease (MND) and 22 with frontotemporal dementia (FTD). Sixty-one patients with sporadic FTLD (sFTLD) matched for age, sex, and disease severity with genetic FTLD (gFTLD) were also included, as well as 52 healthy controls. A whole-brain voxel-based morphometry (VBM) analysis was performed. GM volumes of subcortical and cerebellar structures were obtained.ResultsCompared with controls, GM atrophy on VBM was greater and more diffuse in genetic FTD, followed by sporadic FTD and genetic MND cases, whereas patients with sporadic MND (sMND) showed focal motor cortical atrophy. Patients carrying C9orf72 and GRN mutations showed the most widespread cortical volume loss, in contrast with GM sparing in SOD1 and TARDBP. Globally, patients with gFTLD showed greater atrophy of parietal cortices and thalami compared with sFTLD. In volumetric analysis, patients with gFTLD showed volume loss compared with sFTLD in the caudate nuclei and thalami, in particular comparing C9-MND with sMND cases. In the cerebellum, patients with gFTLD showed greater atrophy of the right lobule VIIb than sFTLD. Thalamic volumes of patients with gFTLD with a C9orf72 mutation showed an inverse correlation with Frontal Behavioral Inventory scores.DiscussionMeasures of deep GM and cerebellar structural involvement may be useful markers of gFTLD, particularly C9orf72-related disorders, regardless of the clinical presentation within the FTLD spectrum.

Where in the Brain is “the Other’s” Hand? Mapping Dysfunctional Neural Networks in Somatoparaphrenia

Somatoparaphrenia refers to the delusional belief, typically observed in right brain-damaged patients, that the contralesional limbs belong to someone else. Here, we aimed to uncover the neural activity associated with this productive, i.e. confabulatory, component in a patient, S.P.P., with a large right-sided lesion of both cortical and subcortical gray and white matter. He claimed that his left paralyzed hand belonged to his mother. In a block-design functional magnetic resonance (fMRI) experiment, S.P.P. imagined that the mother would move her (i.e. his left) hand (condition “mother”). Subtraction of the activity elicited by control conditions (imagery of self-generated movement of either left or right hand) from that in the “mother” condition resulted in the focal activation of the pars opercularis of the right inferior frontal gyrus (rIFG). In a separate, resting-state fMRI experiment with S.P.P. and 21 healthy controls, we examined the functional connectivity of the rIFG and the affected hand somatosensory network to the rest of the brain. We found a negative correlation between the activity in the rIFG and that of Broca area and the temporo-parietal junction in the left hemisphere. Furthermore, the affected hand somatosensory network was disconnected from the left secondary somatosensory cortex. Our results link the productive component of somatoparaphrenia to the activity of crucial hubs for integrating the multimodal signals of the affected hand. Furthermore, they provide the first direct evidence supporting the “left narrator model”, proposed by Halligan et al. (1995), according to which the confabulations of somatoparaphrenia are due to a disconnection of left hemisphere language areas from right hemisphere parieto-temporal cortex.

Surface-based map plasticity of brain regions related to sensory motor and pain information processing after osteonecrosis of the femoral head.

Pain is one of the manifestations of hip disorder and has been proven to lead to the remodeling of somatotopic map plasticity in the cortex. However, most studies are volume-based which may lead to inaccurate anatomical positioning of functional data. The methods that work on the cortical surface may be more sensitive than those using the full brain volume and thus be more suitable for map plasticity study. In this prospective cross-sectional study performed in Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, China, 20 patients with osteonecrosis of the femoral head (12 males and 8 females, aged 56.80 ± 13.60 years) and 20 healthy controls (9 males and 11 females, aged 54.56 ± 10.23 years) were included in this study. Data of resting-state functional magnetic resonance imaging were collected. The results revealed that compared with healthy controls, compared with the healthy controls, patients with osteonecrosis of the femoral head (ONFH) showed significantly increased surface-based regional homogeneity (ReHo) in areas distributed mainly in the left dorsolateral prefrontal cortex, frontal eye field, right frontal eye field, and the premotor cortex and decreased surface-based ReHo in the right primary motor cortex and primary sensory cortex. Regions showing significant differences in surface-based ReHo values between the healthy controls and patients with ONFH were defined as the regions of interests. Seed-based functional connectivity was performed to investigate interregional functional synchronization. When the areas with decreased surface-based ReHo in the frontal eye field and right premotor cortex were used as the regions of interest, compared with the healthy controls, the patients with ONFH displayed increased functional connectivity in the right middle frontal cortex and right inferior parietal cortex and decreased functional connectivity in the right precentral cortex and right middle occipital cortex. Compared with healthy controls, patients with ONFH showed significantly decreased cortical thickness in the para-insular area, posterior insular area, anterior superior temporal area, frontal eye field and supplementary motor cortex and reduced volume of subcortical gray matter nuclei in the right nucleus accumbens. These findings suggest that hip disorder patients showed cortical plasticity changes, mainly in sensorimotor- and pain-related regions. This study was approved by the Medical Ethics Committee of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine (approval No. 2018-041) on August 1, 2018.

Sex differences in brain atrophy and cognitive impairment in Parkinson\u2019s disease patients with and without probable rapid eye movement sleep behavior disorder

BackgroundThe presence of rapid eye movement sleep behavior disorder (RBD) contributes to increase cognitive impairment and brain atrophy in Parkinson’s disease (PD), but the impact of sex is unclear. We aimed to investigate sex differences in cognition and brain atrophy in PD patients with and without probable RBD (pRBD).MethodsMagnetic resonance imaging and cognition data were obtained for 274 participants from the Parkinson's Progression Marker Initiative database: 79 PD with pRBD (PD-pRBD; male/female, 54/25), 126 PD without pRBD (PD-non pRBD; male/female, 73/53), and 69 healthy controls (male/female, 40/29). FreeSurfer was used to obtain volumetric and cortical thickness data.ResultsMales showed greater global cortical and subcortical gray matter atrophy than females in the PD-pRBD group. Significant group-by-sex interactions were found in the pallidum. Structures showing a within-group sex effect in the deep gray matter differed, with significant volume reductions for males in one structure in in PD-non pRBD (brainstem), and three in PD-pRBD (caudate, pallidum and brainstem). Significant group-by-sex interactions were found in Montreal Cognitive Assessment (MoCA) and Symbol Digits Modalities Test (SDMT). Males performed worse than females in MoCA, phonemic fluency and SDMT in the PD-pRBD group.ConclusionMale sex is related to increased cognitive impairment and subcortical atrophy in de novo PD-pRBD. Accordingly, we suggest that sex differences are relevant and should be considered in future clinical and translational research.

Neurocognitive performance in relapsing-remitting multiple sclerosis patients is associated with metabolic abnormalities of the thalamus but not the hippocampus– GABA-edited 1H MRS study

ABSTRACT Objectives Multiple sclerosis (MS) is an inflammatory demyelinating disease that may cause physical disabling as well as cognitive dysfunction. The presented study investigated how the neuropsychological status depends on the thalamus and hippocampus’s metabolic processes, using γ-aminobutyric acid-edited magnetic resonance spectroscopy (GABA-edited 1H MRS) in patients with early MS, and how the results differ from healthy volunteers. Methods We recruited 36 relapsing-remitting (RRMS) MS patients and 22 controls (CON). In addition to common 1H MRS metabolites, such as N-acetyl-aspartate (tNAA), myoinositol (mIns), total choline and creatine (tCr, tCho), we also evaluated GABA and glutamate/glutamine (Glx). Metabolite ratios were correlated with the results of Single-Digit Modality Test (SDMT) and Expanded Disability Status Score (EDSS). Results In the thalamus, GABA ratios (GABA/tCr, GABA/tNAA) were significantly lower in RRMS patients than in CON. Both tCho- and mIns-ratios correlated with lower scores of SDMT but not with EDSS. Metabolic ratios in the hippocampus did not differ between RRMS and CON and did not correlate with any of performed tests. Discussion This study is the first to provide GABA-edited 1H MRS evidence for MS-related metabolic changes of the thalamus and hippocampus. The findings underline the importance of evaluating subcortical grey matter in MS patients to improve understanding of the clinical manifestations of MS and as a potential future target for treatment.

Early Childhood Socioeconomic Status and Cognitive and Adaptive Outcomes at the Transition to Adulthood: The Mediating Role of Gray Matter Development Across Five Scan Waves

BackgroundEarly low socioeconomic status (SES) is associated with poor outcomes in childhood, many of which endure into adulthood. It is critical to determine how early low SES relates to trajectories of brain development and whether these mediate relationships to poor outcomes. We use data from a unique 17-year longitudinal study with five waves of structural brain imaging to prospectively examine relationships between preschool SES and cognitive, social, academic, and psychiatric outcomes in early adulthood. MethodsChildren (n = 216, 50% female, 47.2% non-White) were recruited from a study of early onset depression and followed approximately annually. Family income-to-needs ratios (SES) were assessed when children were ages 3 to 5 years. Volumes of cortical gray and white matter and subcortical gray matter collected across five scan waves were processed using the FreeSurfer Longitudinal pipeline. When youth were ages 16+ years, cognitive function was assessed using the NIH Toolbox, and psychiatric diagnoses, high-risk behaviors, educational function, and social function were assessed using clinician administered and parent/youth report measures. ResultsLower preschool SES related to worse cognitive, high-risk, educational, and social outcomes (|standardized B| = 0.20–0.31, p values < .003). Lower SES was associated with overall lower cortical (standardized B = 0.12, p < .0001) and subcortical gray matter (standardized B = 0.17, p < .0001) volumes, as well as a shallower slope of subcortical gray matter growth over time (standardized B = 0.04, p = .012). Subcortical gray matter mediated the relationship of preschool SES to cognition and high-risk behaviors. ConclusionsThese novel longitudinal data underscore the key role of brain development in understanding the long-lasting relations of early low SES to outcomes in children.

Childhood Adversity and the Brain: Harnessing the Power of Neuroplasticity

In the current issue of Biological Psychiatry, Gehred et al. ( 1 Gehred M.Z. Knodt A.R. Ambler A. Bourassa K.J. Danese A. Elliott M.L. et al. Long-term neural embedding of childhood adversity in a population-representative birth cohort followed for 5 decades. Biol Psychiatry. 2021; 90: 182-193 Abstract Full Text Full Text PDF Scopus (6) Google Scholar ) showcase unique new data and a novel window on the long-term impact of childhood adversity on structural changes in the brain. This report uses data from a by now well-known birth cohort in Dunedin, New Zealand, creatively harnessed over many decades by Moffitt and Caspi. It is a testament to these scholars that they have continuously added to the measurement armamentarium of this project as new relevant measures and technologies have been developed. When the Dunedin study was first launched, neuroimaging did not exist. With the newly added neuroimaging measures along with the measurement of different aspects of development as the sample matured, this birth cohort offers a goldmine of rich data that have so effectively been explored over the years by Moffitt and Caspi and their colleagues. Gehred et al. ( 1 Gehred M.Z. Knodt A.R. Ambler A. Bourassa K.J. Danese A. Elliott M.L. et al. Long-term neural embedding of childhood adversity in a population-representative birth cohort followed for 5 decades. Biol Psychiatry. 2021; 90: 182-193 Abstract Full Text Full Text PDF Scopus (6) Google Scholar ) report that both prospectively ascertained and retrospective measures of childhood adversity were associated with smaller total cortical surface area, average cortical thickness, and smaller subcortical gray matter volume in a birth cohort of 861 participants. The imaging data were acquired when the participants were 45 years of age, with 94% of the original sample participating. Gehred et al. ( 1 Gehred M.Z. Knodt A.R. Ambler A. Bourassa K.J. Danese A. Elliott M.L. et al. Long-term neural embedding of childhood adversity in a population-representative birth cohort followed for 5 decades. Biol Psychiatry. 2021; 90: 182-193 Abstract Full Text Full Text PDF Scopus (6) Google Scholar ) also reported that associations with prospectively ascertained measures of adversity were consistently stronger than those with retrospectively reported adversity. Finally, the findings revealed widely distributed effects throughout the brain with virtually no regional specificity. SEE CORRESPONDING ARTICLE ON PAGE 182 SEE CORRESPONDING ARTICLE ON PAGE 182 Long-term Neural Embedding of Childhood Adversity in a Population-Representative Birth Cohort Followed for 5 DecadesBiological PsychiatryVol. 90Issue 3PreviewChildhood adversity has been previously associated with alterations in brain structure, but heterogeneous designs, methods, and measures have contributed to mixed results and have impeded progress in mapping the biological embedding of childhood adversity. We sought to identify long-term differences in structural brain integrity associated with childhood adversity. Full-Text PDF Open Access

Rates of cognitive impairment in a South African cohort of people with HIV: variation by definitional criteria and lack of association with neuroimaging biomarkers.

There is wide variation in the reported prevalence of cognitive impairment in people with HIV (PWH). Part of this variation may be attributable to different studies using different methods of combining neuropsychological test scores to classify participants as either cognitively impaired or unimpaired. Our aim was to determine, in a South African cohort of PWH (N = 148), (a) how much variation in reported rates was due to method used to define cognitive impairment and (b) which method correlated best with MRI biomarkers of HIV-related brain pathology. Participants completed detailed neuropsychological assessment and underwent 3T structural MRI and diffusion tensor imaging (DTI). We used the neuropsychological data to investigate 20 different methods of determining HIV-associated cognitive impairment. We used the neuroimaging data to obtain volumes for cortical and subcortical grey matter and total white matter and DTI metrics for several white matter tracts. Applying each of the 20 methods to the cognitive dataset resulted in a wide variation (20-97%) in estimated rates of impairment. Logistic regression models showed no method was associated with HIV-related neuroimaging abnormalities as measured by structural volumes or DTI metrics. We conclude that for the population from which this sample was drawn, much of the variation in reported rates of cognitive impairment in PWH is due to the method of classification used, and that none of these methods accurately reflects biological effects of HIV in the brain. We suggest that defining HIV-associated cognitive impairment using neuropsychological test performance only is insufficient; pre-morbid functioning, co-morbidities, cognitive symptoms, and functional impairment should always be considered.