Basal Ganglia Research Articles

Cognitive function in Parkinson's disease: associations with perivascular space in basal ganglia.

Cognitive impairment is one of the most common symptoms of Parkinson's disease (PD), and may be detectable through changes in neural features visualized by magnetic resonance imaging (MRI). Mild cognitive impairment is a transitional state between normal aging and dementia, and early recognition of Parkinson's disease with mild cognitive impairment (PD-MCI) can help improve the quality of life and treatment for patients. This study investigated the association of enlarged perivascular space (EPVS) and white matter hyperintensity (WMH) with PD-MCI. This study aimed to evaluate whether EPVS and WMH can be used as potential MRI markers for PD-MCI. This retrospective study involved 200 patients with PD who underwent cranial MRI in our hospital from April 2021 to April 2022. Patients were divided into those with no cognitive impairment (PD-NCI) or mild cognitive impairment. Uni- and multivariate logistic regression analyzed associations of EPVS, WMH, and clinicodemographic characteristics with cognitive decline. Univariate regression identified severe EPVS in basal ganglia, severe WMH, older age, late-onset, male sex, low educational level, longer duration of disease, low triglycerides, low uric acid, and low scores on the Mini-mental State Exam as risk factors for PD-MCI. After adjusting for clinicodemographic risk factors in multivariate regression, low education level and EPVS in basal ganglia remained risk factors for cognitive impairment. Severe EPVS in basal ganglia and poor education, but not WMH, are independent risk factors of PD-MCI. Our findings suggest that non-invasive detection of EPVS in basal ganglia by MRI may be a valuable early indicator of cognitive decline in PD patients.

Simultaneous Increase of Mean Susceptibility and Mean Kurtosis in the Substantia Nigra as an MRI Neuroimaging Biomarker for Early-Stage Parkinson's Disease: A Systematic Review and Meta-Analysis.

Parkinson's disease (PD) is the second most common neurodegenerative disorder. Early detection is crucial for treatment and slowing disease progression. Simultaneous alterations in mean susceptibility (MS) from quantitative susceptibility mapping (QSM) and mean kurtosis (MK) from diffusion kurtosis imaging (DKI) can serve as reliable neuroimaging biomarkers for early-stage PD (ESPD) in the basal ganglia nuclei, including the substantia nigra (SN), putamen (PUT), globus pallidus (GP), and caudate nucleus (CN). Systematic review and meta-analysis. One hundred eleven patients diagnosed with ESPD and 81 healthy controls (HCs) were included from four studies that utilized both QSM and DKI in both subject groups. Three-dimensional multi-echo gradient echo sequence for QSM and spin echo planar imaging sequence for DKI at 3 Tesla. A systematic review and meta-analysis using PRISMA guidelines searched PubMed, Web of Science, and Scopus. Random-effects model, standardized mean difference (SMD) to compare MS and MK between ESPD patients and HCs, I2 statistic for heterogeneity, Newcastle-Ottawa Scale (NOS) for risk of bias, and Egger's test for publication bias. A P-value <0.05 was considered significant. MS values were significantly higher in SN (SMD 0.72, 95% CI 0.31 to 1.12), PUT (SMD 0.68, 95% CI 0.29 to 1.07), and GP (SMD 0.53, 95% CI 0.19 to 0.87) in ESPD patients compared to HCs. CN did not show a significant difference in MS values (P = 0.15). MK values were significantly higher only in SN (SMD = 0.72, 95% CI 0.16 to 1.27). MK values were not significantly different in PUT (P = 1.00), GP (P = 0.97), and CN (P = 0.59). Studies had high quality (NOS 7-8) and no publication bias (P = 0.967). Simultaneous use of MS and MK may be useful as an early neuroimaging biomarker for ESPD detection and its differentiation from HCs, with significant differences observed in the SN. 2 TECHNICAL EFFICACY: Stage 2.

Proline-rich transmembrane protein 2 regulates the magnitude and frequency of dopamine release by repetitive neuronal stimuli in the striatum of L-dopa-treated mice.

Mutations in proline-rich transmembrane protein 2 (PRRT2) cause paroxysmal kinesigenic dyskinesia (PKD). Recently, we reported that a Prrt2 mutation exacerbated L-dopa-induced motor deficits in mice, suggesting that the basal ganglia might contribute to PKD pathology. Here, we demonstrated that the Prrt2 mutation enhanced depolarization stimuli-induced extracellular dopamine levels in the mouse striatum, which were attenuated by repeated stimulation. L-dopa administration maintained high dopamine levels in Prrt2-KI mice even during repetitive stimuli but did not affect dopamine levels in wild-type mice. Thus, the enhanced and prolonged responsiveness of dopamine release in nigrostriatal dopaminergic neurons to sequential excitation may be partially implicated in Prrt2-related dyskinesia.

Seizure onset and offset pattern determine the entrainment of the cortex and substantia nigra in the nonhuman primate model of focal temporal lobe seizures.

Temporal lobe epilepsy (TLE) is the most common form of drug-resistant epilepsy. A major focus of human and animal studies on TLE network has been the limbic circuit. However, there is also evidence suggesting an active role of the basal ganglia in the propagation and control of temporal lobe seizures. Here, we characterize the involvement of the substantia nigra (SN) and somatosensory cortex (SI) during temporal lobe (TL) seizures induced by penicillin injection in the hippocampus (HPC) of two nonhuman primates. The seizure onset and offset patterns were manually classified and spectral power and coherence were calculated. We then compared the 3-second segments recorded in pre-ictal, onset, offset and post-ictal periods based on the seizure onset and offset patterns. Our results demonstrated an involvement of the SN and SI dependent on the seizure onset and offset pattern. We found that low amplitude fast activity (LAF) and high amplitude slow activity (HAS) onset patterns were associated with an increase in activity of the SN while the change in activity was limited to LAF seizures in the SI. However, the increase in HPC/SN coherence was specific to the farther-spreading LAF onset pattern. As for the role of the SN in seizure cessation, we observed that the coherence between the HPC/SN was reduced during burst suppression (BS) compared to other termination phases. Additionally, we found that this coherence returned to normal levels after the seizure ended, with no significant difference in post-ictal periods among the three types of seizure offsets. This study constitutes the first demonstration of TL seizures entraining the SN in the primate brain. Moreover, these findings provide evidence that this entrainment is dependent on the onset and offset pattern and support the hypothesis that the SN might play a role in the maintenance and termination of some specific temporal lobe seizure.

Low frequency oscillations in mid-rostral dorsolateral prefrontal cortex support response inhibition.

Executive control of movement enables inhibiting impulsive responses critical for successful navigation of the environment. Circuits mediating stop commands involve prefrontal and basal ganglia structures with fMRI evidence demonstrating increased activity during response inhibition in dorsolateral prefrontal cortex (dlPFC) - often ascribed to maintaining task attentional demands. Using direct intraoperative cortical recordings in male and female human subjects, we investigated oscillatory dynamics along the rostral-caudal axis of dlPFC during a modified Go/No-go task, probing components of both proactive and reactive motor control. We assessed whether cognitive control is topographically organized along this axis and observed that low frequency power increased prominently in mid-rostral dlPFC when inhibiting and delaying responses. These findings provide evidence for a key role for mid-rostral dlPFC low frequency oscillations in sculpting motor control.Significance Statement This work offers insights into the neural mechanisms underlying executive control of movement. By employing intraoperative cortical recordings, our study uncovers the specific role of low frequency oscillations in the mid-rostral dlPFC during response inhibition. We demonstrate a topographical organization of low frequency power along the rostral-caudal axis of the dlPFC. This finding supports existing work suggesting the PFC hierarchy may be rooted in cognitive demand and extends it by showing this hierarchy can be represented by low frequency oscillations. Finally, understanding the spatial and temporal dynamics of inhibitory control may enable more effective neuromodulation therapies in the future, such as those aimed at Parkinson Disease patients to address impulsivity.

White Matter Microstructural Changes Using Ultra-Strong Diffusion Gradient MRI in Adult-Onset Idiopathic Focal Cervical Dystonia.

Adult-onset idiopathic focal cervical dystonia (AOIFCD) involves abnormal posturing of the cervical musculature and, in some individuals, an associated head tremor. Existing neuroimaging studies have implicated key motor networks. However, measures used to date lack specificity toward underlying pathophysiologic differences. We aim to assess white matter motor pathways for localized, microstructural differences, which may aid in understanding underlying mechanisms. Individuals diagnosed with AOIFCD and an age- and sex-matched control group were prospectively recruited through the Welsh Movement Disorders Research Network. All participants underwent in-depth clinical phenotyping and MRI (structural and diffusion sequences) using ultra-strong diffusion gradients. Tractography (whole-tract median values) and tractometry (along tract profiling) were performed for key white matter motor pathways assessing diffusion kurtosis imaging (DKI), neurite orientation dispersion and density imaging (NODDI), and standard model parameters. Groups were compared using linear model analysis with Bonferroni multiple comparison correction. Fifty participants with AOIFCD and 30 healthy control participants were recruited, with 46 with AOIFCD and 30 healthy controls included for analysis (33 without head tremor, 13 with head tremor). Significant differences were observed in the anterior thalamic radiations (lower mid-tract fractional anisotropy [estimate = -0.046, p = 3.07 × 10-3], radial kurtosis [estimate = -0.165, p = 1.42 × 10-4], f-intra-axonal signal fraction [estimate = -0.044, p = 2.78 × 10-3], p2 orientation coherence [estimate = -0.043, p = 1.64 × 10-3], higher Orientation Dispersion Index [ODI, estimate = 0.023, p = 2.22 × 10-3]) and thalamopremotor tracts (higher mid-tract mean kurtosis [estimate = 0.064, p = 7.56 × 10-4], lower Neurite Density Index [estimate = 0.062, p = 2.1 × 10-3], higher distal tract ODI [estimate = 0.062, p = 3.1 × 10-3], lower f [estimate = -0.1, p = 2.3 × 10-3], and striatopremotor tracts [proximal lower f: estimate = -0.075, p = 1.06 × 10-3]). These measures correlated with clinical measures: dystonia duration (right thalamopremotor distal ODI: r = -0.9, p = 1.29 × 10-14), psychiatric symptoms (obsessive compulsive symptoms: left anterior thalamic radiation p2 r = 0.92, p = 2.797 × 10-11), sleep quality (Sleep Disorders Questionnaire Score: left anterior thalamic radiation ODI: r = -0.84, p = 4.84 × 10-11), pain (left anterior thalamic radiation ODI: r = -0.89, p = 1.4 × 10-13), and cognitive functioning (paired associated learning task p2, r = 0.94, p = 6.68 × 10-20). Overall, localized microstructural differences were identified within tracts linking the prefrontal and premotor cortices with thalamic and basal ganglia regions, suggesting pathophysiologic processes involve microstructural aberrances of motor system modulatory pathways, particularly involving intra-axonal and fiber orientation dispersion measures.

Ngfr+ cholinergic projection from SI/nBM to mPFC selectively regulates temporal order recognition memory.

Acetylcholine regulates various cognitive functions through broad cholinergic innervation. However, specific cholinergic subpopulations, circuits and molecular mechanisms underlying recognition memory remain largely unknown. Here we show that Ngfr+ cholinergic neurons in the substantia innominate (SI)/nucleus basalis of Meynert (nBM)-medial prefrontal cortex (mPFC) circuit selectively underlies recency judgements. Loss of nerve growth factor receptor (Ngfr-/- mice) reduced the excitability of cholinergic neurons in the SI/nBM-mPFC circuit but not in the medial septum (MS)-hippocampus pathway, and impaired temporal order memory but not novel object and object location recognition. Expression of Ngfr in Ngfr-/- SI/nBM restored defected temporal order memory. Fiber photometry revealed that acetylcholine release in mPFC not only predicted object encounters but also mediated recency judgments of objects, and such acetylcholine release was absent in Ngfr-/- mPFC. Chemogenetic and optogenetic inhibition of SI/nBM projection to mPFC in ChAT-Cre mice diminished mPFC acetylcholine release and deteriorated temporal order recognition. Impaired cholinergic activity led to a depolarizing shift of GABAergic inputs to mPFC pyramidal neurons, due to disturbed KCC2-mediated chloride gradients. Finally, potentiation of acetylcholine signaling upregulated KCC2 levels, restored GABAergic driving force and rescued temporal order recognition deficits in Ngfr-/- mice. Thus, NGFR-dependent SI/nBM-mPFC cholinergic circuit underlies temporal order recognition memory.

Repetitive transcranial magnetic stimulation reshaped the dynamic reconfiguration of the executive and reward networks in individuals with tobacco use disorder

BackgroundStudies have demonstrated the potential of repetitive transcranial magnetic stimulation (rTMS) to decrease smoking cravings in individuals with tobacco use disorder (TUD). However, the neural features underlying the effects of rTMS treatment, especially the dynamic attributes of brain networks associated with the treatment, remain unclear. MethodsUsing dynamic functional connectivity analysis, this study first explored the differences in dynamic functional network features between 60 subjects with TUD and 64 nonsmoking healthy controls (HCs). Then, the left dorsolateral prefrontal cortex (DLPFC) was targeted for a five-day course of rTMS treatment in the 60 subjects with TUD (active rTMS in 42 subjects and sham treatment in 18 subjects). We explored the effect of rTMS on the dynamic network features associated with rTMS by comparing the actively treated group and the sham group. ResultsCompared to nonsmokers, TUD subjects exhibited an increased integration coefficient between the frontoparietal network (FPN) and the basal ganglia network (BGN) and a reduced integration coefficient between the medial frontal network (MFN) and the FPN. Analysis of variance revealed that rTMS treatment reduced the integration coefficient between the FPN and BGN and improved the recruitment coefficient of the FPN. LimitationsThis study involved a limited sample of young male smokers, and the findings may not generalize to older smokers or female smokers with an extensive history of smoking. ConclusionrTMS treatment of the left DLPFC exhibited significant effectiveness in restructuring the neural circuits associated with TUD while significantly mitigating smoking cravings.

Enlarged Perivascular Spaces Are Independently Associated with High Pulse Wave Velocity: A Cross-Sectional Study.

Recent studies have demonstrated an association between pulse wave velocity (PWV), cerebral small vessel disease (SVD), and cognitive impairment such as Alzheimer's disease. However, the association between brachial-ankle PWV and enlarged perivascular spaces (EPVS), one component of cerebral SVD remains controversial. To investigate the relationship between brachial-ankle PWV and EPVS severity in participants without dementia. We performed a cross-sectional study of data of 74 participants from sub-analysis of ongoing research. We assessed cognitive function, brachial-ankle PWV, and brain magnetic resonance imaging (MRI) features. Using brain MRI, EPVS were separately assessed as basal ganglia (BG)-EPVS or centrum semiovale (CSO)-EPVS on the basis of their location. The relationship between EPVS severity and brachial-ankle PWV was evaluated using multivariable ordinal logistic regression analyses. We analyzed 74 participants (women: 47%, mean age: 73 years, mild cognitive impairment [MCI]: 74%). Compared with participants with normal cognition, those with MCI were more likely to have both severe BG-EPVS and severe CSO-EPVS. In multivariable analyses, high brachial-ankle PWV and age were independently associated with BG-EPVS severity (odds ratio [95% confidence interval]: 1.19 [1.02-1.38], 1.09 [1.01-1.17], respectively), whereas only age was independently associated with CSO-EPVS severity. A causal mediation analysis under a counterfactual approach revealed a significant pure natural indirect effect of brachial-ankle PWV on MCI that was mediated by BG-EPVS (estimate: 1.04, 95% CI: 1.01-1.12, p = 0.006). Brachial-ankle PWV was associated with BG-EPVS severity. High PWV may cause cerebrovascular pulsatility, which accelerates BG-EPVS and may worsen cognitive impairment.

Development and validation of a perivascular space segmentation method in multi-center datasets

BackgroundPerivascular spaces (PVS) visible on magnetic resonance imaging (MRI) are significant markers associated with various neurological diseases. Although quantitative analysis of PVS may enhance sensitivity and improve consistency across studies, the field lacks a universally validated method for analyzing images from multi-center studies. MethodsWe annotated PVS on multi-center 3D T1-weighted (T1w) images acquired using scanners from three major vendors (Siemens, General Electric, and Philips). A neural network, mcPVS-Net (multi-center PVS segmentation network), was trained using data from 40 subjects and then tested in a separate cohort of 15 subjects. We assessed segmentation accuracy against ground truth masks tailored for each scanner vendor. Additionally, we evaluated the agreement between segmented PVS volumes and visual scores for each scanner. We also explored correlations between PVS volumes and various clinical factors such as age, hypertension, and white matter hyperintensities (WMH) in a larger sample of 1020 subjects. Furthermore, mcPVS-Net was applied to a new dataset comprising both T1w and T2-weighted (T2w) images from a United Imaging scanner to investigate if PVS volumes could discriminate between subjects with differing visual scores. We also compared the mcPVS-Net with a previously published method that segments PVS from T1 images. ResultsIn the test dataset, mcPVS-Net achieved a mean DICE coefficient of 0.80, with an average Precision of 0.81 and Recall of 0.79, indicating good specificity and sensitivity. The segmented PVS volumes were significantly associated with visual scores in both the basal ganglia (r = 0.541, p < 0.001) and white matter regions (r = 0.706, p < 0.001), and PVS volumes were significantly different among subjects with varying visual scores. Segmentation performance was consistent across different scanner vendors. PVS volumes exhibited significant associations with age, hypertension, and WMH. In the United Imaging scanner dataset, PVS volumes showed good associations with PVS visual scores evaluated on either T1w or T2w images. Compared to a previously published method, mcPVS-Net showed a higher accuracy and improved PVS segmentation in the basal ganglia region. ConclusionThe mcPVS-Net demonstrated good accuracy for segmenting PVS from 3D T1w images. It may serve as a useful tool for future PVS research.

A multi-modal framework improves prediction of tissue-specific gene expression from a surrogate tissue

Tissue-specific analysis of the transcriptome is critical to elucidating the molecular basis of complex traits, but central tissues are often not accessible. We propose a methodology, Multi-mOdal-based framework to bridge the Transcriptome between PEripheral and Central tissues (MOTPEC). Multi-modal regulatory elements in peripheral blood are incorporated as features for gene expression prediction in 48 central tissues. To demonstrate the utility, we apply it to the identification of BMI-associated genes and compare the tissue-specific results with those derived directly from surrogate blood. MOTPEC models demonstrate superior performance compared with both baseline models in blood and existing models across the 48 central tissues. We identify a set of BMI-associated genes using the central tissue MOTPEC-predicted transcriptome data. The MOTPEC-based differential gene expression (DGE) analysis of BMI in the central tissues (including brain caudate basal ganglia and visceral omentum adipose tissue) identifies 378 genes overlapping the results from a TWAS of BMI, while only 162 overlapping genes are identified using gene expression in blood. Cellular perturbation analysis further supports the utility of MOTPEC for identifying trait-associated gene sets and narrowing the effect size divergence between peripheral blood and central tissues. The MOTPEC framework improves the gene expression prediction accuracy for central tissues and enhances the identification of tissue-specific trait-associated genes. This research is supported by the National Natural Science Foundation of China 82204118 (D.Z.), the seed funding of the Key Laboratory of Intelligent Preventive Medicine of Zhejiang Province (2020E10004), the National Institutes of Health (NIH) Genomic Innovator Award R35HG010718 (E.R.G.), NIH/NHGRI R01HG011138 (E.R.G.), NIH/NIA R56AG068026 (E.R.G.), NIH Office of the Director U24OD035523 (E.R.G.), and NIH/NIGMS R01GM140287 (E.R.G.).

A Comparison of Pre- and Post-Treatment Cranial MRI Characteristics in Patients with Pediatric Epilepsy Receiving Levetiracetam.

Background and Objectives: This study was performed for the purpose of assessing whether antiepileptic levetiracetam treatment produces a change in brain volumes in children with epilepsy. To that end, we compared the volumes of the basal ganglia (caudate nucleus, putamen, globus, hip-pocampus, and thalamus) at magnetic resonance imaging (MRI) before and after treatment (months 18-24) in pediatric epilepsy patients using levetiracetam. Materials and Methods: This retrospective study involved a volumetric comparison of patients presenting to the Balikesir University Medical Faculty pediatric neurology clinic between 01.08.2019 and 01.11.2023 and diagnosed with epilepsy, and who underwent cranial MRI before and 18-24 months after treatment at the radiology department. The demographic and clinical characteristics (age, sex, family history of epilepsy, type of epilepsy, and EEG features (normal, abnormal, epileptiform)) of the patients included in the study were recorded. Results: The comparison of basal ganglia volumes at cranial MRI before and at months 18-24 of treatment revealed significant differences in the left caudate nucleus, right putamen, left putamen, left globus pallidus, right thalamus, left thalamus, and right hippocampal regions. Conclusions: In conclusion, differing findings are encountered at cranial imaging in patients with epilepsy, depending on the seizure frequency, activity, and the type of antiepileptic drugs used. This study compared basal ganglia volumes on cranial MRIs taken before and 18-24 months after treatment in pediatric epilepsy patients using levetiracetam. A significant increase was observed in the volumes of basal ganglia (caudate nucleus, putamen, globus pallidus, hippocampus, and thalamus) on the MRIs of pediatric epilepsy patients using levetiracetam.

Causal effect of cerebral small vessel disease on unexplained dizziness: A Mendelian randomization study

BackgroundPrevious cohort studies have suggested an association between cerebral small vessel disease (cSVD) and “unexplained dizziness”. The causality of this link remains uncertain, but it would be of significant clinical importance, considering the substantial number of patients presenting with unexplained dizziness is large. We aimed to investigate the causal effect of cSVD-related phenotypes on unexplained dizziness using a Mendelian randomization approach. MethodsGenetic instruments for each cSVD-related phenotype - white matter hyperintensity (WMH) volume, lacunar stroke (LS), perivascular spaces (PVS), and cerebral microbleeds (CMBs) - as well as unexplained dizziness were identified through large-scale genome-wide association studies. We conducted 2-sample Mendelian randomization analyses. The random-effects inverse-variance weighted (IVW) method was chosen for the primary analysis. For sensitivity analyses, we employed the weighted-median, MR-Egger, MR pleiotropy residual sum and outlier (MR-PRESSO), and leave-one-out analysis methods were implemented for the sensitivity analyses. ResultsWe successfully identified a significant causal effect of WMH volume on unexplained dizziness (odds ratio [95% CI], 1.12 [1.01–1.23]). However, we were unable to detect any significant causal effects of the other cSVD-related phenotypes on unexplained dizziness, with odds ratios [95% CI] of 1.03 [0.98–1.09] for LS, 0.75 [0.55–1.02] for white matter PVS, 1.02 [0.68–1.52] for basal ganglia PVS, 0.80 [0.43–1.51] for hippocampal PVS, 0.95 [0.90–1.00] for lobar CMBs, and 0.97 [0.92–1.01] for mixed CMBs respectively. The results from the sensitivity analyses were generally consistent with those of the primary analyses. ConclusionsThis MR study supports a causal relationship between WMH, a phenotype associated with cSVD, and the risk of unexplained dizziness, but does not support such a relationship between other cSVD-related phenotypes and unexplained dizziness. These findings require further validation through randomized controlled trials, larger cohort studies, and MR studies based on more extensive GWASs.

Exploring the Relationship between Abnormal Communication Efficiency of Cerebral Cortex and Multiple Cognitive Functions in Mild Subcortical Stroke: A Resting-State fMRI Study.

The purpose of this study was to explore the specific regions of abnormal cortical communication efficiency in patients with mild subcortical stroke and to investigate the relationship between these communication efficiency abnormalities and multidimensional cognition. The research involved 35 patients with mild strokes affecting the basal ganglia and 29 healthy controls (HC). Comprehensive neuroimaging and neuropsychological assessments were conducted. Stroke patients were categorized into post-stroke cognitive impairment (PSCI) (MoCA ≤ 22) and non-cognitively impaired stroke patients (NPSCI) (MoCA ≥ 23) based on their cognitive performance. Additionally, 22 patients were reassessed three months later. PSCI patients, compared to HC and NPSCI groups, had significantly higher communication efficiency in specific brain regions. A notable finding was the significant correlation between increased communication efficiency in the medioventral occipital cortex and multidimensional cognitive decline. However, this increased communication efficiency in PSCI patients lessened during the three-month follow-up period. the heightened communication efficiency in the medio-ventral occipital cortex may represent a compensatory mechanism for cognitive impairment in PSCI patients, which undergoes adjustment three months after stroke.

Loss of synaptic density in nucleus basalis of meynert indicates distinct neurodegeneration in Alzheimer's disease: the RJNB-D study.

The nucleus basalis of Meynert (NBM) is known to play a crucial role in the development and pathogenesis of Alzheimer's Disease (AD), particularly the cholinergic system within the NBM. However, the relationship between synaptic loss in the NBM and the clinical profile of AD remains unclear. In our study, we included 44 Aβ-negative normal controls (CN) and 76 Aβ-positive participants with cognitive impairment (CI). All participants underwent structural and diffusion magnetic resonance imaging (MRI), as well as positron emission tomography (PET) imaging to measure synaptic vesicle glycoprotein 2A (SV2A) levels (Trial registration: NCT05623124. Registered 21 November 2022). The SV2A standardized uptake value ratios (SUVR) distribution in the NBM of CN participants was used as the reference norm. We investigated the association between NBM synaptic density and clinical performance, traditional AD biomarkers, and white matter tracts that passed the NBM. Participants with cognitive impairment (CI) who had NBM synaptic density below 1.5 standard deviations (SD) or 0.5 SD of the norm exhibited worse cognitive performance compared to cognitively normal (CN) individuals. Crucially, the extent of deviation in synaptic density from the norm was directly proportional to the severity of cognitive impairment and neurodegeneration biomarkers. Furthermore, among patients with cognitive impairment, synaptic loss in the NBM was associated with potential impairment in the density and organization of neurites within the white matter tracts connected to the NBM. Finally, neurite density index in the medial tracts may play a mediating role in the relationship between NBM synaptic density and MMSE scores. The extent that synaptic density in NBM deviated from the norm suggested the extent of worse cognitive performance and severe neurodegeneration. Furthermore, cognitive impairment associated with synaptic loss in the NBM may be mediated by its pathological impact on NBM white matter tracts.

Evaluating the impact of tubular retractors in glioma surgery: A systematic review and meta-analysis

BackgroundAchieving safe, maximal tumor resection in gliomas can be challenging due to the tumor’s intricate relationship with surrounding structures. Tubular retractors offer a minimally invasive approach, preserving functional pathways and reducing complications. To assess their efficacy and safety, we conducted a systematic review and meta-analysis. MethodsA search across databases identified 26 studies meeting inclusion criteria, encompassing 106 patients with various glioma types and tumor locations. ResultsAmong 26 eligible studies, 15 provided sufficient data on 106 patients (median age: 50.5 years). Glioblastoma multiforme constituted 52.4 % of tumors, followed by IDH-mutant astrocytomas at 31.0 %. Tumor locations varied, with intraventricular and thalamic involvement in 16.3 % (16/98) of cases, followed by temporal (12.2 %), frontal and occipital (each 8.16 %), basal ganglia (8.16 %), parietal (7.14 %), optic pathway (2.04 %), and caudate nucleus (1.02 %) involvement. VyCor and Brainpath retractors were most used (22.6 % and 21.7 %, respectively). Tubular retractors were often combined with the exoscope (35.9 %). Gross total resection (GTR) was achieved in 69.4 % of cases, near-total resection (NTR) in 5.1 %, and subtotal resection/partial resection (STR/PR) in 25.5 %. Mean extent of resection (EOR) significantly differed between GTR and STR/NTR/PR groups (p<0.001). Postoperative complications included visual deficits (6.38 %), hemiparesis or weakness (2.13 %), multiple complications (1.06 %), and other unspecified complications (3.19 %). ConclusionTubular retractors are a valuable intraoperative adjunct and component of the surgical armamentarium for glioma surgery allowing bimanual operative techniques to manage hemostasis directly with excellent surgical outcomes and an acceptable complication profile.

Psychological Factors Affecting Assertiveness in Subjects with Parkinson's Disease.

Background/Objectives: Assertiveness, defined as the positive affirmation of oneself, encompasses the ability to refuse requests, express anger, disagree or oppose others, show affection, and uphold personal beliefs without causing conflict. Deficits in assertive behavior are often linked to pathological changes in the basal ganglia and prefrontal dopaminergic systems, commonly observed in Parkinson's disease (PD), and are predictive of poor clinical outcomes. Psychological factors such as mood alterations and cognitive dysfunction may also impact assertiveness. This study investigated the psychological factors influencing assertiveness in individuals with PD. Methods: A cross-sectional study was conducted, involving 160 patients with PD attending a movement disorders outpatient clinic. The participants underwent assessment using a battery of standardized neuropsychological tests to evaluate cognitive function, assertiveness, mood, dysarthria, and quality of life (QoL). Results: All dimensions of assertiveness correlated with depression and anxiety. Individuals experiencing mood disturbances may struggle to express themselves assertively. Similarly, some dimensions of assertiveness correlated also with the QoL, indicating that, overall, well-being affects assertive behavior. Gender emerged as a significant influencer of assertiveness across all dimensions. Specifically, in subjects with PD, the male gender was associated with lower scores in assertiveness compared to women. No significant correlations were found between assertiveness and dysarthria. Conclusions: The findings highlight the importance of adopting a holistic approach to PD management, addressing not only motor symptoms but also psychological challenges which patients may encounter in their daily lives.

Usefulness of combined pseudo-continuous arterial spin labelling and spectroscopic analysis in schizophrenic Egyptian population sample

BackgroundSchizophrenia is a prevalent psychiatric disorder that affects 1% of the global population. Schizophrenia frequently begins in late adolescence or early adulthood, causing significant educational, social, and economic costs for people and society. Functional neuroimaging research on schizophrenia physiopathology has been beneficial. Arterial spin labelling (ASL) is one of functional magnetic resonance imaging (fMRI) technologies that assess brain function without radiation. ASL uses magnetic resonance (MR) imaging to quantify tissue-level brain perfusion non-invasively. Arterial spin labelling (ASL) is one of the functional magnetic resonance imaging (fMRI) technologies that assess the brain function without radiation hazards. ASL uses magnetic resonance (MR) imaging to quantify tissue-level brain perfusion non-invasively. Many publications were performed on role of different advanced MRI techniques in schizophrenia, but our study insisted on the added value of combined ASL and MRS over the conventional MRI in schizophrenic Egyptian population sample.Aim of the workThe purpose of this work was to evaluate the added value of combined ASL-perfusion MRI and MRS in schizophrenic patients.MethodsThis prospective case–control study was carried out on two groups: First group was 30 patients who were diagnosed clinically as schizophrenic patients, and second group was 20 healthy volunteers as a control group for comparison in the period from August 2021 till July 2022.ResultsThe majority of newly diagnosed cases had significant higher positive symptoms than chronic cases. According to arterial spin labelling (ASL) data, rCBF was noticed to be reduced in anterior cingulate, frontal lobe, and parietal lobe of both patients’ subgroups but more significant in chronically ill patients. Convergent results of decreased rCBF were also found in the parietal lobe and occipital lobe. Magnetic resonance spectroscopic analysis showed that NAA was decreased in the anterior cingulate cortex, thalami and basal ganglia of the newly diagnosed cases more than chronic cases. The ASL-MRI perfusion accurately detected the hypo-perfusion of different brain regions with sensitivity 100%, specificity 66.67%, positive predictive value 96.43%, negative predictive value 100%, and accuracy 96.67%, while MR spectroscopy showed sensitivity 100%, specificity 33.33%, positive predictive value 93.10%, negative predictive value 100%, and accuracy 93.33% in evaluation of changes of brain metabolites.ConclusionASL is a promising functional MRI technique that can produce together with MRS quantitative information about the metabolites of different brain regions. The ASL-MRI appears as a reliable non-invasive technique to measure cerebral blood flow and identify decreased rCBF without any contrast administration, and it could be repeatable which helps in early diagnosis as well as follow-up of the progression of the disease.

Inhibitory basal ganglia nuclei differentially innervate pedunculopontine nucleus subpopulations and evoke opposite motor and valence behaviors.

The canonical basal ganglia model predicts that the substantia nigra pars reticulata (SNr) and the globus pallidus externa (GPe) will have specific effects on locomotion: the SNr inhibiting locomotion and the GPe enhancing it. In this manuscript, we use in vivo optogenetics to show that a projection-defined neural subpopulation within each structure exerts non-canonical effects on locomotion. These non-canonical subpopulations are defined by their projection to the pedunculopontine nucleus (PPN) and mediate opposing effects on reward. To understand how these structures differentially modulate the PPN, we use ex vivo whole-cell recording with optogenetics to comprehensively dissect the SNr and GPe connections to regionally- and molecularly-defined populations of PPN neurons. The SNr inhibits all PPN subtypes, but most strongly inhibits caudal glutamatergic neurons. The GPe selectively inhibits caudal glutamatergic and GABAergic neurons, avoiding both cholinergic and rostral cells. This circuit characterization reveals non-canonical basal ganglia pathways for locomotion and valence.

Clinical Characteristics and Outcome of Spontaneous Intracerebral Hemorrhage

Background: Stroke is the second leading cause of death and disability globally. Intracerebral hemorrhage represents a prominent subtype comprising 10-20% of all strokes and posing substantial challenges, particularly in low-income countries. This study aims to unravel the clinical profile and outcomes of spontaneous ICH patients at our institute. Materials and Methods: This is a prospective observational study conducted at the department of Neurosurgery Nobel Medical College Teaching Hospital, Biratnagar, Nepal over a period of one and half years. Results: In the Present study, a total of 285 populations were studied, where there was male preponderance with the mean age of 57.9 years. Commonest clinical manifestation was sudden onset headache (75.1%) followed by decreased level of consciousness. Hypertension was the commonest cause of ICH. Basal ganglia were the primary location of bleed. The statistical analysis revealed a significant difference in the mean clot volume between survivors and non-survivors. There was a strong association between ventricular extension of hematoma and outcome. Surgical hematoma evacuation was performed in 30.9% of cases. Favorable outcomes, defined by a modified Rankin Scale score of 0-3, were achieved in 58.9% of participants. Conclusion: Age, sudden onset headache, and hypertension predict mortality in primary intracerebral hemorrhage (ICH), particularly with advanced age linked to poorer outcomes. A Glasgow Coma Score less than eight increases mortality risk, while clot volume and intraventricular extension play crucial roles in ICH outcome.