Gray Matter Atrophy in a 6-OHDA-induced Model of Parkinson's Disease.

INTRODUCTION: Magnetic resonance imaging (MRI) based brain morphometric changes in unilateral 6-hydroxydopamine (6-OHDA) induced Parkinson's disease (PD) model can be elucidated using voxel-based morphometry (VBM), study of alterations in gray matter volume and Machine Learning (ML) based analyses. METHODS: We investigated gray matter atrophy in 6-OHDA induced PD model as compared to sham control using statistical and ML based analysis. VBM and atlas-based volumetric analysis was carried out at regional level. Support vector machine (SVM)-based algorithms wherein features (volume) extracted from (a) each of the 150 brain regions (b) statistically significant features (only) and (c) volumes of each cluster identified after application of VBM (VBM_Vol) were used for training the decision model. The lesion of the 6-OHDA model was validated by estimating the net contralateral rotational behaviour by the injection of apomorphine drug and motor impairment was assessed by rotarod and open field test. RESULTS AND DISCUSSION: In PD, gray matter volume (GMV) atrophy was noted in bilateral cortical and subcortical brain regions, especially in the internal capsule, substantia nigra, midbrain, primary motor cortex and basal ganglia-thalamocortical circuits in comparison with sham control. Behavioural results revealed an impairment in motor performance. SVM analysis showed 100% classification accuracy, sensitivity and specificity at both 3 and 7 weeks using VBM_Vol. CONCLUSION: Unilateral 6-OHDA induced GMV changes in both hemispheres at 7th week may be associated with progression of the disease in the PD model. SVM based approaches provide an increased classification accuracy to elucidate GMV atrophy.

Evaluation of Cognitive Deficits in Adults with Type 1 Diabetes Stratified by the Age of Diabetes Onset: A Cross-Sectional Study.

INTRODUCTION: Type 1 diabetes (T1DM) is associated with cognitive deficits, and age at diagnosis is thought to play a substantial role. However, there are limited data for the cognitive performance in young adults, in relation to the age of diabetes onset. The lack of information is particularly striking in the context of developing regions. METHODS: This cross-sectional study was performed from August 2018 to July 2020. We included adult participants with T1DM, stratified by the age of diabetes onset (till 6 years of age, between 7 to 12 years of age, and 13 to < 18 years of age) and compared them with the control group (no diabetes or pre-diabetes). We filled a structured case record proforma for all participants and recorded relevant socio-demographic and medical details. Detailed neuropsychological assessment with 13 psychological tests representing four cognitive domains was carried-(1) attention, working memory and executive functions; (2) learning and memory; (3) visuoperceptual functions; and (4) information processing speed. RESULTS: We evaluated 100 individuals, 73 (men 48.0%) with T1DM and 27 (men 51.9%) without T1DM. After adjustment for age, gender and education, the mean differences in composite Z scores (for the four cognitive domains) between participants with T1DM and without T1DM were 0.08 for attention, working memory and executive functions (p = 0.614); 0.07 for learning and memory (p = 0.694); 0.05 for visuoperceptual (p = 0.784); and 0.22 for information processing speed (p = 0.305). No significant differences were found for the three subgroups of individuals with T1DM, when compared with the control group. Effect size (Cohen's d) for the individual tests (n = 13) ranged from - 0.36 to + 0.39, and none of the comparisons were statistically significant. Amongst the participants with T1DM, higher education had a significant positive association with three of the four cognitive domains evaluated. CONCLUSIONS: To conclude, our findings suggest minimal differences in the cognitive functioning of patients with T1DM with different age of onset of diabetes compared to healthy controls, when evaluated in early adulthood. This is possibly the first study from South Asia with an in-depth and comprehensive assessment of cognitive functions in patients with T1DM, using a detailed neuropsychological battery.

Structural atrophy of central autonomic network correlates with the functional attributes of autonomic nervous system in spinocerebellar ataxia patients.

OBJECTIVE: Spinocerebellar ataxia (SCA) is a neurodegenerative disorder in which, autonomic dysfunction is a common manifestation. Brain area atrophy also involves the areas comprising central autonomic network (CAN) in SCA. Structural atrophy of CAN and autonomic dysfunction should go hand in hand. But this important relationship has not been studied to date. Therefore, using SCA as a disease model, the present study has been designed to explore the plausible correlations between the brain areas of CAN and clinical autonomic function modalities in SCA patients. MATERIALS AND METHODS: 3D T1-weighted scans were acquired on 3T MRI, analyzed by FreeSurfer software in genetically confirmed forty-nine SCA patients (SCA1 = 18, SCA2 = 25 and SCA3 = 6). Heart rate variability (HRV), blood pressure variability (BPV), baroreflex sensitivity (BRS), and autonomic reactivity tests were used for evaluation of autonomic nervous system. Additionally, autonomic dysfunction scoring was done using composite autonomic severity score (CASS). RESULTS: On correlation analysis, the study showed the association of atrophic cortical and subcortical brain areas (predominantly prefrontal cortex, bilateral middle temporal, left cuneus, left lingual and left caudate) with altered clinical autonomic function parameters in SCA patients. These areas were primarily comprised of sympathetic and parasympathetic brain areas of CAN. One of the key brain areas of CAN - left cuneus was found to be associated with both HRV (r = 0.295, p = 0.040) and BRS (r = 0.326, p = 0.022). CONCLUSION: A characteristic pattern of association between particular brain areas of CAN and clinical autonomic function parameters was observed in SCA patients.

Visual Cortex Alterations in Early and Late Blind Subjects During Tactile Perception.

Involvement of visual cortex varies during tactile perception tasks in early blind (EB) and late blind (LB) human subjects. This study explored differences in sensory motor networks associated with tactile task in EB and LB subjects and between children and adolescents. A total of 40 EB subjects, 40 LB subjects, and 30 sighted controls were recruited in two subgroups: children (6-12 years) and adolescents (13-19 years). Data were acquired using a 3T MR scanner. Analyses of blood oxygen level dependent (BOLD), functional connectivity (FC), correlation, and post hoc test for multiple comparisons were carried out. Difference in BOLD activity was observed in EB and LB groups in visual cortex during tactile perception, with increased FC of visual with dorsal attention and sensory motor networks in EB. EB adolescents exhibited increased connectivity with default mode and salience networks when compared with LB. Functional results correlated with duration of training, suggestive of better performance in EB. Alteration in sensory and visual networks in EB and LB correlated with duration of tactile training. Age of onset of blindness has an effect in cross-modal reorganization of visual cortex in EB and multimodal in LB in children and adolescents.

Smart dual T1 MRI-optical imaging agent based on a rhodamine appended Fe(III)-catecholate complex.

A rhodamine appended Fe(iii)-catecholate complex Fe(RhoCat)3 is reported as a smart dual-modal T1 MRI-optical imaging probe. The high spin Fe(iii) coordination sphere and rhodamine unit act as MRI and optical reporters, respectively. The probe showed a r1-relaxivity of 4.37 mM-1 s-1 at 1.41 T via the interaction of second sphere water molecules to coordinated oxygen atoms. It produced an enhanced signal intensity of phantom images on the 7.0 T animal research MRI/MRS scanner at 25 °C and pH 7.3. The interaction of the probe with bovine serum albumin (BSA) significantly improved r1 relaxivity (7.09 mM-1 s-1). Moreover, the optical imaging reporter rhodamine moiety exhibited sensitivity towards biomolecule nitric oxide (NO) and acidic pH via the formation of a ring-opened tautomer of rhodamine, wherein the r1 relaxivity of the probe was enhanced to 5.19 mM-1 s-1 for NO and slightly decreased for acidic pH. Further, the probe visualized NO in adenocarcinoma gastric (AGS) cells via a turn-on fluorescence mechanism with 80% cell viability. Thus, Fe(RhoCat)3 is demonstrated as a potential dual "MRI-ON and Fluorescence-ON" molecular imaging probe to visualize the NO molecule and acidic pH in the tumour microenvironment.

Mechanism of selective attention: fMRI study of face-word Stroop task performance.

Selective attention is the cognitive process of selecting and processing the task relevant information and ignoring the task irrelevant information. Though the neural substrates involved in this cognitive process are well established, the mechanism of selection process is the point of contention. To study the effect of selection process on the information processing we performed functional neuroimaging on 23 healthy righthanded male subjects while performing a modified face word stroop task. The word processing area did not show any attention dependent changes in the level of activity whereas the activity of face processing area was higher when the faces were target, but there was no decrease in baseline activity when faces were distractors. Our results suggest that during selective attention there is no biasing of sensory processing for automatically processed stimuli like words whereas there is amplification of task relevant information when stimuli are processed in controlled manner.

Functional mapping in PD and PSP for sustained phonation and phoneme tasks.

AIM: To elucidate the central basis of articulatory speech disorders in Parkinsonian syndromes using functional magnetic resonance imaging (fMRI). METHODS: Twenty-two patients with Parkinson's disease (PD) and 18 with progressive supranuclear palsy (PSP) were clinically evaluated for speech dysfunction. Functional magnetic resonance imaging (fMRI) was carried out in these patients using sustained phonation and phoneme tasks. Individual and group analysis using SPM2 was done for eight patients with PD, 7 with PSP and 6 healthy controls. SETTING: Tertiary Medical Teaching Institute. RESULTS: For sustained phonation paradigm, superior temporal gyrus area was activated in PD patients, and occipital cortex in PSP subjects in comparison to controls. For phoneme paradigm, the patients with PD recruit lingual gyrus obviating the need for more efforts for the task. Also wider areas as well as more clusters were activated in PD patients compared to controls. Lingual gyrus was found to be strongly activated in PSP patients. Reduced activation of the primary areas with recruitment of remote areas was another prominent finding in PSP. Due to excessive motion (>1.5 mm, >1 degrees ) in all the MSA patients, they could not be considered for analysis. CONCLUSION: The failure of the executive fronto-striatal network would lead to increased activation of other areas in PD, but in PSP, there is a widespread cortical dysfunction.