Genetic underpinnings of risky behaviour relate to altered neuroanatomy.

Previous research points to the heritability of risk-taking behaviour. However, evidence on how genetic dispositions are translated into risky behaviour is scarce. Here, we report a genetically informed neuroimaging study of real-world risky behaviour across the domains of drinking, smoking, driving and sexual behaviour in a European sample from the UK Biobank (N = 12,675). We find negative associations between risky behaviour and grey-matter volume in distinct brain regions, including amygdala, ventral striatum, hypothalamus and dorsolateral prefrontal cortex (dlPFC). These effects are replicated in an independent sample recruited from the same population (N = 13,004). Polygenic risk scores for risky behaviour, derived from a genome-wide association study in an independent sample (N = 297,025), are inversely associated with grey-matter volume in dlPFC, putamen and hypothalamus. This relation mediates roughly 2.2% of the association between genes and behaviour. Our results highlight distinct heritable neuroanatomical features as manifestations of the genetic propensity for risk taking.

Discrete changes in brain volume after deep brain stimulation in patients with Parkinson's disease.

OBJECTIVES: Deep brain stimulation (DBS), targeting the subthalamic nucleus (STN) and globus pallidus interna, is a surgical therapy with class 1 evidence for Parkinson's disease (PD). Bilateral DBS electrodes may be implanted within a single operation or in separate staged surgeries with an interval of time that varies patient by patient. In this study, we used the variation in the timing of implantation from the first to the second implantation allowing for examination of potential volumetric changes of the basal ganglia in patients with PD who underwent staged STN DBS. METHODS: Thirty-two patients with a mean time interval between implantations of 141.8 (±209.1; range: 7-700) days and mean duration of unilateral stimulation of 244.7 (±227.7; range: 20-672) days were included in this study. Using volumetric analysis of whole hemisphere and subcortical structures, we observed whether implantation or stimulation affected structural volume. RESULTS: We observed that DBS implantation, but not the duration of stimulation, induced a significant reduction of volume in the caudate, pallidum, putamen and thalamus ipsilateral to the implanted hemisphere. These findings were not dependent on the trajectory of the implanted electrode nor on first surgery pneumocephalus (0.07%: %Δ for intracranial volume between first and second surgery). In addition, unique regional atrophy differences were evident in each of the structures. CONCLUSION: Our results demonstrate that DBS implantation surgery may affect hemisphere volume at the level of subcortical structures connected to the surgical target.

Sleep Onset Problems and Subcortical Development in Infants Later Diagnosed With Autism Spectrum Disorder.

OBJECTIVE: Sleep patterns in children with autism spectrum disorder (ASD) appear to diverge from typical development in the second or third year of life. Little is known, however, about the occurrence of sleep problems in infants who later develop ASD and possible effects on early brain development. In a longitudinal neuroimaging study of infants at familial high or low risk for ASD, parent-reported sleep onset problems were examined in relation to subcortical brain volumes in the first 2 years of life. METHODS: A total of 432 infants were included across three study groups: infants at high risk who developed ASD (N=71), infants at high risk who did not develop ASD (N=234), and infants at low risk (N=127). Sleep onset problem scores (derived from an infant temperament measure) were evaluated in relation to longitudinal high-resolution T1 and T2 structural imaging data acquired at 6, 12, and 24 months of age. RESULTS: Sleep onset problems were more common at 6-12 months among infants who later developed ASD. Infant sleep onset problems were related to hippocampal volume trajectories from 6 to 24 months only for infants at high risk who developed ASD. Brain-sleep relationships were specific to the hippocampus; no significant relationships were found with volume trajectories of other subcortical structures examined (the amygdala, caudate, globus pallidus, putamen, and thalamus). CONCLUSIONS: These findings provide initial evidence that sleep onset problems in the first year of life precede ASD diagnosis and are associated with altered neurodevelopmental trajectories in infants at high familial risk who go on to develop ASD. If replicated, these findings could provide new insights into a potential role of sleep difficulties in the development of ASD.

Brain Volume Changes in Patients with Acute Brain Dysfunction Due to Sepsis.

BACKGROUND: Sepsis-induced brain dysfunction (SIBD) is often encountered in sepsis patients and is related to increased morbidity. No specific tests are available for SIBD, and neuroimaging findings are often normal. In this study, our aim was to analyze the diagnostic value of volumetric analysis of the brain structures and to find out its significance as a prognostic measure. METHODS: In this prospective observational study, brain magnetic resonance imaging (MRI) sections of 25 consecutively enrolled SIBD patients (17 with encephalopathy and 8 with coma) and 22 healthy controls underwent volumetric evaluation by an automated segmentation method. RESULTS: Ten SIBD patients had normal MRI, and 15 patients showed brain lesions or atrophy. The most prominent volume reduction was found in cerebral and cerebellar white matter, cerebral cortex, hippocampus, and amygdala, whereas deep gray matter regions and cerebellar cortex were relatively less affected. SIBD patients with normal MRI showed significantly reduced volumes in hippocampus and cerebral white matter. Caudate nuclei, putamen, and thalamus showed lower volume values in non-survivor SIBD patients, and left putamen and right thalamus showed a more pronounced volume reduction in coma patients. CONCLUSIONS: Volumetric analysis of the brain appears to be a sensitive measure of volumetric changes in SIBD. Volume reduction in specific deep gray matter regions might be an indicator of unfavorable outcome.

Children with epilepsy demonstrate macro- and microstructural changes in the thalamus, putamen, and amygdala.

PURPOSE: Despite evidence for macrostructural alteration in epilepsy patients later in life, little is known about the underlying pathological or compensatory mechanisms at younger ages causing these alterations. The aim of this work was to investigate the impact of pediatric epilepsy on the central nervous system, including gray matter volume, cerebral blood flow, and water diffusion, compared with neurologically normal children. METHODS: Inter-ictal magnetic resonance imaging data was obtained from 30 children with epilepsy ages 1-16 (73% F, 27% M). An atlas-based approach was used to determine values for volume, cerebral blood flow, and apparent diffusion coefficient in the cerebral cortex, hippocampus, thalamus, caudate, putamen, globus pallidus, amygdala, and nucleus accumbens. These values were then compared with previously published values from 100 neurologically normal children using a MANCOVA analysis. RESULTS: Most brain volumes of children with epilepsy followed a pattern similar to typically developing children, except for significantly larger putamen and amygdala. Cerebral blood flow was also comparable between the groups, except for the putamen, which demonstrated decreased blood flow in children with epilepsy. Diffusion (apparent diffusion coefficient) showed a trend towards higher values in children with epilepsy, with significantly elevated diffusion within the thalamus in children with epilepsy compared with neurologically normal children. CONCLUSION: Children with epilepsy show statistically significant differences in volume, diffusion, and cerebral blood flow within their thalamus, putamen, and amygdala, suggesting that epilepsy is associated with structural changes of the central nervous system influencing brain development and potentially leading to poorer neurocognitive outcomes.

Effect of disease-modifying therapies on subcortical gray matter atrophy in multiple sclerosis.

BACKGROUND: The effects of disease-modifying therapies (DMTs) on region-specific brain atrophy in multiple sclerosis (MS) are unclear. OBJECTIVE: To determine the effects of higher versus lower efficacy DMTs on rates of brain substructure atrophy in MS. METHODS: A non-randomized, observational cohort of people with MS followed with annual brain magnetic resonance imaging (MRI) was evaluated retrospectively. Whole brain, subcortical gray matter (GM), cortical GM, and cerebral white matter (WM) volume fractions were obtained. DMTs were categorized as higher (DMT-H: natalizumab and rituximab) or lower (DMT-L: interferon-beta and glatiramer acetate) efficacy. Follow-up epochs were analyzed if participants had been on a DMT for ⩾6 months prior to baseline and had at least one follow-up MRI while on DMTs in the same category. RESULTS: A total of 86 DMT epochs (DMT-H: n = 32; DMT-L: n = 54) from 78 participants fulfilled the study inclusion criteria. Mean follow-up was 2.4 years. Annualized rates of thalamic (-0.15% vs -0.81%; p = 0.001) and putaminal (-0.27% vs -0.73%; p = 0.001) atrophy were slower during DMT-H compared to DMT-L epochs. These results remained significant in multivariate analyses including demographics, clinical characteristics, and T2 lesion volume. CONCLUSION: DMT-H treatment may be associated with slower rates of subcortical GM atrophy, especially of the thalamus and putamen. Thalamic and putaminal volumes are promising imaging biomarkers in MS.

Widespread subcortical grey matter degeneration in primary lateral sclerosis: a multimodal imaging study with genetic profiling.

BACKGROUND: Primary lateral sclerosis (PLS) is a low incidence motor neuron disease which carries a markedly better prognosis than amyotrophic lateral sclerosis (ALS). Despite sporadic reports of extra-motor symptoms, PLS is widely regarded as a pure upper motor neuron disorder. The post mortem literature of PLS is strikingly sparse and very little is known of subcortical grey matter pathology in this condition. METHODS: A prospective imaging study was undertaken with 33 PLS patients, 117 healthy controls and 100 ALS patients to specifically assess the integrity of subcortical grey matter structures and determine whether PLS and ALS have divergent thalamic, hippocampal and basal ganglia signatures. Volumetric, morphometric, segmentation and vertex-wise analyses were carried out in the three study groups to evaluate the integrity of thalamus, hippocampus, caudate, amygdala, pallidum, putamen and accumbens nucleus in each hemisphere. The hippocampus was further parcellated to characterise the involvement of specific subfields. RESULTS: Considerable thalamic, caudate, and hippocampal atrophy was detected in PLS based on both volumetric and vertex analyses. Significant volume reductions were also detected in the accumbens nuclei. Hippocampal atrophy in PLS was dominated by dentate gyrus, hippocampal tail and CA4 subfield volume reductions. The morphometric comparison of ALS and PLS cohorts revealed preferential medial bi-thalamic pathology in PLS compared to the predominant putaminal degeneration detected in ALS. Another distinguishing feature between ALS and PLS was the preferential atrophy of the amygdala in ALS. CONCLUSIONS: PLS is associated with considerable subcortical grey matter degeneration and due to the extensive extra-motor involvement, it should no longer be regarded a pure upper motor neuron disorder. Given its unique pathological features and a clinical course which differs considerably from ALS, dedicated research studies and disease-specific therapeutic strategies are urgently required in PLS.

Extensive cerebellar and thalamic degeneration in spinocerebellar ataxia type 10.

INTRODUCTION: Spinocerebellar ataxia type 10 (SCA10) is a hereditary neurodegenerative disorder caused by repeat expansions in the ATXN10 gene. Patients present with cerebellar ataxia frequently accompanied by seizures. Even though loss of cerebellar Purkinje neurons has been described, its brain degeneration pattern is unknown. Our aim was to characterize the gray and white matter degeneration patterns in SCA10 patients and the association with clinical features. METHODS: We enrolled 18 patients with molecular diagnosis of SCA10 and 18 healthy individuals matched for age and sex. All participants underwent brain MRI including high-resolution anatomical and diffusion images. Whole-brain Tract-Based Spatial Statistics (TBSS) and Voxel-Based Morphometry (VBM) were performed to identify white and grey matter degeneration respectively. A second analysis in the cerebellum identified the unbiased pattern of degeneration. Motor impairment was assessed using the SARA Scale. RESULTS: TBSS analysis in the patient group revealed white matter atrophy exclusively in the cerebellum. VBM analysis showed extensive grey matter degeneration in the cerebellum, brainstem, thalamus, and putamen. Significant associations between cerebellar degeneration and SARA scores were found. Additionally, degeneration in thalamic GM and WM in the cerebellar lobule VI were significantly associated with the presence of seizures. CONCLUSION: The results show that besides cerebellum and brainstem, brain degeneration in SCA10 includes predominantly the putamen and thalamus; involvement of the latter is strongly associated with seizures. Analysis of the unbiased degeneration pattern in the cerebellum suggests lobules VIIIb, IX, and X as the primary cerebellar targets of the disease, which expands to the anterior lobe in later stages.

Running in the Family? Structural Brain Abnormalities and IQ in Offspring, Siblings, Parents, and Co-twins of Patients with Schizophrenia.

Structural brain abnormalities and cognitive deficits have been reported in patients with schizophrenia and to a lesser extent in their first-degree relatives (FDRs). Here we investigated whether brain abnormalities in nonpsychotic relatives differ per type of FDR and how these abnormalities are related to intelligent quotient (IQ). Nine hundred eighty individuals from 5 schizophrenia family cohorts (330 FDRs, 432 controls, 218 patients) were included. Effect sizes were calculated to compare brain measures of FDRs and patients with controls, and between each type of FDR. Analyses were repeated with a correction for IQ, having a nonpsychotic diagnosis, and intracranial volume (ICV). FDRs had significantly smaller ICV, surface area, total brain, cortical gray matter, cerebral white matter, cerebellar gray and white matter, thalamus, putamen, amygdala, and accumbens volumes as compared with controls (ds < -0.19, q < 0.05 corrected). Offspring showed the largest effect sizes relative to the other FDRs; however, none of the effects in the different relative types survived correction for multiple comparisons. After IQ correction, all effects disappeared in the FDRs after correction for multiple comparisons. The findings in FDRs were not explained by having a nonpsychotic disorder and were only partly explained by ICV. FDRs show brain abnormalities that are strongly covarying with IQ. On the basis of consistent evidence of genetic overlap between schizophrenia, IQ, and brain measures, we suggest that the brain abnormalities in FDRs are at least partly explained by genes predisposing to both schizophrenia risk and IQ.

Contribution of normal aging to brain atrophy in MS.

OBJECTIVE: To identify the top brain regions affected by MS-specific atrophy (i.e., atrophy in excess of normal aging) and to test whether normal aging and MS-specific atrophy increase or decrease in these regions with age. METHODS: Six hundred fifty subjects (2,790 MRI time points) were analyzed: 520 subjects with relapse-onset MS from a 5-year prospective cohort with annual standardized 1-mm 3D T1-weighted images (3DT1s; 2,483 MRIs) and 130 healthy controls with longitudinal 3DT1s (307 MRIs). Rates of change in all FreeSurfer regions (v5.3) and Structural Image Evaluation Using Normalization of Atrophy (SIENA) were estimated with mixed-effects models. All FreeSurfer regions were ranked by the MS-specific atrophy slope/standard error ratio (ßMS × time/SEßMS × time). In the top regions, age was added as an effect modifier to test whether MS-specific atrophy varied by age. RESULTS: The top-ranked regions were all gray matter structures. For SIENA, normal aging increased from 0.01%/y at age 30 years to -0.31%/y at age 60 years (-0.11% ± 0.032%/decade, p < 0.01), whereas MS-specific atrophy decreased from -0.38%/y at age 30 years to -0.12%/y at age 60 years (0.09% ± 0.035%/decade, p = 0.01). Similarly, in the thalamus, normal aging increased from -0.15%/y at age 30 years to -0.62%/y at age 60 years (-0.16% ± 0.079%/decade, p < 0.05), and MS-specific atrophy decreased from -0.59%/y at age 30 years to -0.05%/y at age 60 years (0.18% ± 0.08%/decade, p < 0.05). In the putamen and caudate, normal aging and MS-specific atrophy did not vary by age. CONCLUSIONS: For SIENA and thalamic atrophy, the contribution of normal aging increases with age, but does not change in the putamen and caudate. This may have substantial implications to understand the biology of brain atrophy in MS.

Regional subcortical shape analysis in premanifest Huntington's disease.

Huntington's disease (HD) involves preferential and progressive degeneration of striatum and other subcortical regions as well as regional cortical atrophy. It is caused by a CAG repeat expansion in the Huntingtin gene, and the longer the expansion the earlier the age of onset. Atrophy begins prior to manifest clinical signs and symptoms, and brain atrophy in premanifest expansion carriers can be studied. We employed a diffeomorphometric pipeline to contrast subcortical structures' morphological properties in a control group with three disease groups representing different phases of premanifest HD (far, intermediate, and near to onset) as defined by the length of the CAG expansion and the participant's age (CAG-Age-Product). A total of 1,428 magnetic resonance image scans from 694 participants from the PREDICT-HD cohort were used. We found significant region-specific atrophies in all subcortical structures studied, with the estimated abnormality onset time varying from structure to structure. Heterogeneous shape abnormalities of caudate nuclei were present in premanifest HD participants estimated furthest from onset and putaminal shape abnormalities were present in participants intermediate to onset. Thalamic, hippocampal, and amygdalar shape abnormalities were present in participants nearest to onset. We assessed whether the estimated progression of subcortical pathology in premanifest HD tracked specific pathways. This is plausible for changes in basal ganglia circuits but probably not for changes in hippocampus and amygdala. The regional shape analyses conducted in this study provide useful insights into the effects of HD pathology in subcortical structures.

Smaller subcortical volume in Parkinson patients with rapid eye movement sleep behavior disorder.

Parkinson disease (PD) patients with rapid eye movement (REM) sleep behavior disorder (RBD) have worse motor symptoms and non-motor symptoms than patients without RBD. The aim of this study was to examine underlying differences in brain structure from a network perspective. Baseline data were obtained from Parkinson's Progression Markers Initiative (PPMI) participants. We divided PD patients and healthy controls (HC) into RBD positive and RBD negative using a cutoff score of ≥5 on the RBD screening questionnaire. HC with probable RBD were excluded. We first carried out a region-of-interest analysis of structural MRIs using voxel-based morphometry to study volumetric differences for the putamen, thalamus and hippocampus in a cross-sectional design. Additionally, an exploratory whole-brain analysis was performed. To study group differences from a network perspective, we then performed a 'seed-based' analysis of structural covariance, using the bilateral dorsal-caudal putamen, mediodorsal thalamus and anterior hippocampus as seed regions. The volume of the right putamen was smaller in PD patients with RBD. RBD symptom severity correlated negatively with volume of the right putamen, left hippocampus and left thalamus. We did not find any differences in structural covariance between PD patients with and without RBD. Presence of RBD and severity of RBD symptoms in PD are associated with smaller volumes of the putamen, thalamus and hippocampus.

The asymmetry of neural symptoms in Wilson's disease patients detecting by diffusion tensor imaging, resting-state functional MRI, and susceptibility-weighted imaging.

Objective: To investigate the cause of the motor asymmetry in Wilson's disease (WD) patients using functional MRI. Methods: Fifty patients with WD and 20 age-matched healthy controls were enrolled. Neurological symptoms were scored using the modified Young Scale. All study subjects underwent diffusion tensor imaging (DTI), susceptibility-weighted imaging (SWI), and resting-state functional MRI (rs-fMRI) of the brain. Six regions of interest (ROI) were chosen. Fiber volumes between ROIs on DTI, corrected phase (CP) values on SWI, amplitude of low-frequency fluctuation (ALFF), and regional homogeneity (REHO) values on rs-fMRI were determined. Asymmetry index (right or left value/left or right value) was evaluated. Results: Asymmetry of rigidity, tremor, choreic movement, and gait abnormality (asymmetry index = 1.33, 1.39, 1.36, 1.40), fiber tracts between the GP and substantia nigra (SN), GP and PU, SN and thalamus (TH), SN and cerebellum, head of the caudate nucleus (CA) and SN, PU and CA, CA and TH, TH and cerebellum (asymmetry index = 1.233, 1.260, 1.269, 1.437, 1.503, 1.138, 1.145, 1.279), CP values in the TH, SN (asymmetry index = 1.327, 1.166), ALFF values, and REHO values of the TH (asymmetry index = 1.192, 1.233) were found. Positive correlation between asymmetry index of rigidity and fiber volumes between the GP and SN, SN and TH (r = .221, .133, p = .043, .036), and tremor and fiber volumes between the CA and TH (r = .045, p = .040) was found. Conclusions: The neurological symptoms of patients with WD were asymmetry. The asymmetry of fiber projections may be the main cause of motor asymmetry in patients with WD.

Cerebral Imaging Markers of GBA and LRRK2 Related Parkinson's Disease and Their First-Degree Unaffected Relatives.

Cerebral atrophy has been detected in patients with Parkinson's disease (PD) both with and without dementia, however differentiation based on genetic status has thus far not yielded robust findings. We assessed cortical thickness and subcortical volumes in a cohort of PD patients and healthy controls carriers of the G2019S mutation in the LRRK2 gene and the common GBA mutations, in an attempt to determine whether genetic status influences structural indexes. Cortical thickness and subcortical volumes were computed and compared between six groups of participants; idiopathic PD, GBA-PD, LRRK2-PD, non-manifesting non-carriers (NMNC), GBA-non-manifesting carriers (NMC) and LRRK2-NMC utilizing the FreeSurfer software program. All participants were cognitively intact based on a computerized cognitive assessment battery. Fifty-seven idiopathic PD patients, 9 LRRK2-PD, 12 GBA-PD, 49 NMNC, 41 LRRK2-NMC and 14 GBA-NMC participated in this study. Lower volumes among patients with PD compared to unaffected participants were detected in bilateral hippocampus, nucleus accumbens, caudate, thalamus, putamen and amygdala and the right pallidum (p = 0.016). PD patients demonstrated lower cortical thickness indexes in a majority of regions assessed compared with non-manifesting participants. No differences in cortical thickness and subcortical volumes were detected within each of the groups of participants based on genetic status. Mutations in the GBA and LRRK2 genes are not important determinants of cortical thickness and subcortical volumes in both patients with PD and non-manifesting participants. PD is associated with a general reduction in cortical thickness and sub-cortical atrophy even in cognitively intact patients.

Attention and processing speed performance in multiple sclerosis is mostly related to thalamic volume.

Cognitive impairment (CI), mainly involving attention and processing speed (A-PS), is a common and disabling symptom in multiple sclerosis (MS). Symbol Digit Modalities Test (SDMT) is one of the more sensitive and reliable tests to assess A-PS deficits in MS. Structural MRI correlates of A-PS in MS still need to be clarified. This study aimed to investigate, in a large group of MS patients, the relationship between regional gray matter (GM) atrophy and SDMT performance. 125 relapsing remitting MS patients and 52 healthy controls (HC) underwent a 3 T-MRI protocol including high-resolution 3D-T1 imaging. All subjects underwent a neurological evaluation and SDMT. A Voxel Based Morphometry analysis was performed to assess: 1) correlations between regional GM volume and SDMT performance in MS patients; 2) regional differences in GM volume between MS patients and HC. Thalamic, putamen and cerebellar volumes were also calculated using FIRST tool from the FMRIB Software Library. A linear regression analysis was performed to assess the contribution of each one of these structures to A-PS performance. A significant negative correlation was found between regional GM volume and SDMT score at the level of the thalamus, cerebellum, putamen, and occipital cortex in MS patients. Thalamus, cerebellum and putamen also showed significant GM atrophy in MS patients compared to HC. Thalamic atrophy is also an independent and additional contributor to A-PS deficits in MS patients. These findings support the role of thalamus as the most relevant GM structure subtending A-PS performance in MS, as measured by SDMT.

Automated segmentation of cerebral deep gray matter from MRI scans: effect of field strength on sensitivity and reliability.

BACKGROUND: The cerebral subcortical deep gray matter nuclei (DGM) are a common, early, and clinically-relevant site of atrophy in multiple sclerosis (MS). Robust and reliable DGM segmentation could prove useful to evaluate putative neuroprotective MS therapies. The objective of the study was to compare the sensitivity and reliability of DGM volumes obtained from 1.5T vs. 3T MRI. METHODS: Fourteen patients with MS [age (mean, range) 50.2 (32.0-60.8) years, disease duration 18.4 (8.2-35.5) years, Expanded Disability Status Scale score 3.1 (0-6), median 3.0] and 15 normal controls (NC) underwent brain 3D T1-weighted paired scan-rescans at 1.5T and 3T. DGM (caudate, thalamus, globus pallidus, and putamen) segmentation was obtained by the fully automated FSL-FIRST pipeline. Both raw and normalized volumes were derived. RESULTS: DGM volumes were generally higher at 3T vs. 1.5T in both groups. For raw volumes, 3T showed slightly better sensitivity (thalamus: p = 0.02; caudate: p = 0.10; putamen: p = 0.02; globus pallidus: p = 0.0004; total DGM: p = 0.01) than 1.5T (thalamus: p = 0.05; caudate: p = 0.09; putamen: p = 0.03; globus pallidus: p = 0.0006; total DGM: p = 0.02) for detecting DGM atrophy in MS vs. NC. For normalized volumes, 3T but not 1.5T detected atrophy in the globus pallidus in the MS group. Across all subjects, scan-rescan reliability was generally very high for both platforms, showing slightly higher reliability for some DGM volumes at 3T. Raw volumes showed higher reliability than normalized volumes. Raw DGM volume showed higher reliability than the individual structures. CONCLUSIONS: These results suggest somewhat higher sensitivity and reliability of DGM volumes obtained from 3T vs. 1.5T MRI. Further studies should assess the role of this 3T pipeline in tracking potential MS neurotherapeutic effects.

T2 relaxation time measurements in the brains of scalded rats.

This study aimed to evaluate the T2 relaxation time of the brain in severely scalded rats using a magnetic resonance (MR) T2 mapping sequence, and to investigate the correlation between T2 relaxation time and plasma glucose level. Twenty-eight Wistar rats were randomly divided into the scalded group (n=21) and control group (n=7). Magnetic resonance scans were performed with T1WI, T2WI, and T2-mapping sequences in the scalded group; the scans were performed 1 day prior to scalding and 1, 3, 5, and 7 days post-scalding; in addition, identical MR scans were performed in the control group at the same time points. T2-maps were generated and T2 relaxation times were acquired from the following brain regions: the hippocampus, thalamus, caudate-putamen, and cerebrum. Pathological changes of the hippocampus were observed. The plasma glucose level of each rat was measured before each MR scan, and a correlation analysis was performed between T2 relaxation time and plasma glucose level. We found that conventional T1WI and T2WI did not reveal any abnormal signals or morphological changes in the hippocampus, thalamus, caudate-putamen, or cerebrum post-scalding. Both the T2 relaxation times of the selected brain regions and plasma glucose levels increased 1, 3, and 5 days post-scalding, and returned to normal levels 7 days post-scalding. The most marked increase of T2 relaxation time was found in the hippocampus; similar changes were also revealed in the thalamus, caudate-putamen, and cerebrum. No correlation was found between T2 relaxation time and plasma glucose level in scalded rats. Pathological observation of the hippocampus showed edema 1, 3, and 5 days post-scalding, with recovery to normal findings at 7 days post-scalding. Thus, we concluded that T2 mapping is a sensitive method for detecting and monitoring scald injury in the rat brain. As the hippocampus is the main region for modulating a stress reaction, it showed significantly increased water content along with an increased plasma glucose level post-scalding.

Decreased subcortical volumes in alcohol dependent individuals: effect of polysubstance use disorder.

Chronic alcohol use has widespread effects on brain morphometry. Alcohol dependent individuals are often diagnosed with comorbid substance use disorders. Alterations in brain morphometry may be different in individuals that are dependent on alcohol alone and individuals dependent on alcohol and other substances. We examined subcortical brain volumes in 37 individuals with alcohol dependence only (ADO), 37 individuals with polysubstance use disorder (PS) and 37 healthy control participants (HC). Participants underwent a structural MR scan and a model-based segmentation tool was used to measure the volume of 14 subcortical regions (bilateral thalamus, caudate, putamen, globus pallidus, hippocampus, amygdala and nucleus accumbens). Compared to HC, ADO had smaller volume in the bilateral hippocampus, right nucleus accumbens and right thalamus. PS only had volume reductions in the bilateral thalamus compared to HC. PS had a larger right caudate compared to ADO. Subcortical volume was negatively associated with drinking measures only in the ADO group. This study confirms the association between alcohol dependence and reductions in subcortical brain volume. It also suggests that polysubstance use interacts with alcohol use to produce limited subcortical volume reduction and at least one region of subcortical volume increase. These findings indicate that additional substance use may mask damage through inflammation or may function in a protective manner, shielding subcortical regions from alcohol-induced damage.

Neuroimaging abnormalities in clade C HIV are independent of Tat genetic diversity.

Controversy remains regarding the neurotoxicity of clade C human immunodeficiency virus (HIV-C). When examined in preclinical studies, a cysteine to serine substitution in the C31 dicysteine motif of the HIV-C Tat protein (C31S) results in less severe brain injury compared to other viral clades. By contrast, patient cohort studies identify significant neuropsychological impairment among HIV-C individuals independent of Tat variability. The present study clarified this discrepancy by examining neuroimaging markers of brain integrity among HIV-C individuals with and without the Tat substitution. Thirty-seven HIV-C individuals with the Tat C31S substitution, 109 HIV-C individuals without the Tat substitution (C31C), and 34 HIV- controls underwent 3T structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). Volumes were determined for the caudate, putamen, thalamus, corpus callosum, total gray matter, and total white matter. DTI metrics included fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD). Tracts of interest included the anterior thalamic radiation (ATR), cingulum bundle (CING), uncinate fasciculus (UNC), and corpus callosum (CC). HIV+ individuals exhibited smaller volumes in subcortical gray matter, total gray matter and total white matter compared to HIV- controls. HIV+ individuals also exhibited DTI abnormalities across multiple tracts compared to HIV- controls. By contrast, neither volumetric nor diffusion indices differed significantly between the Tat C31S and C31C groups. Tat C31S status is not a sufficient biomarker of HIV-related brain integrity in patient populations. Clinical attention directed at brain health is warranted for all HIV+ individuals, independent of Tat C31S or clade C status.

Age-related differences in the structural complexity of subcortical and ventricular structures.

It has been well established that the volume of several subcortical structures decreases in relation to age. Different metrics of cortical structure (e.g., volume, thickness, surface area, and gyrification) have been shown to index distinct characteristics of interindividual differences; thus, it is important to consider the relation of age to multiple structural measures. Here, we compare age-related differences in subcortical and ventricular volume to those differences revealed with a measure of structural complexity, quantified as fractal dimensionality. Across 3 large data sets, totaling nearly 900 individuals across the adult lifespan (aged 18-94 years), we found greater age-related differences in complexity than volume for the subcortical structures, particularly in the caudate and thalamus. The structural complexity of ventricular structures was not more strongly related to age than volume. These results demonstrate that considering shape-related characteristics improves sensitivity to detect age-related differences in subcortical structures.