History of Peripartum Depression Moderates the Association Between Estradiol Polygenic Risk Scores and Basal Ganglia Volumes in Major Depressive Disorder.

BACKGROUND: The neurobiological differences between women who have experienced a peripartum episode and those who have only had episodes outside of this period are not well understood. METHODS: 64 parous female patients with major depressive disorder that have either a positive (n=30) or negative (n=34) history of peripartum depression (PPD) underwent MRI acquisition to obtain structural brain images. An independent two-sample t-test comparing patients with and without a history of PPD was performed using voxel-based morphometry analysis (VBM). Additionally, polygenic risk scores (PRSs) for estradiol were calculated and a moderation analysis was conducted between 3 estradiol PRSs and PPD history status on extracted cluster volumes using IBM SPSS PROCESS macro. RESULTS: The VBM analysis identified larger grey matter volumes in bilateral clusters encompassing the putamen, pallidum, caudate, and thalamus in patients with PPD history compared to patients without a history. The moderation analysis identified a significant interaction of 2 estradiol PRSs and PPD history on grey matter cluster volumes with a positive effect in PPD women and a negative effect in women with no history of PPD. CONCLUSIONS: Our findings demonstrate that women who have experienced a peripartum episode are neurobiologically distinct from women who have no history of PPD in a cluster within the basal ganglia, an area important for motivation, decision-making, and emotional processing. Furthermore, we show that the genetic load for estradiol has a differing effect in this area based on PPD status which supports the claim that PPD is associated with sensitivity to sex steroid hormones.

The relationship between the extent of posterior limb of the internal capsule damage measured by non-contrast computed tomography and clinical outcomes after basal ganglia hemorrhage.

Assessing the extent of damage to the posterior limb of the internal capsule (PLIC) is important for early prediction of clinical outcomes in intracerebral hemorrhage (ICH) patients. Currently, using MRI to reconstruct the extent of damage to PLIC is not suitable for quick assessment of prognosis in emergency settings. We aimed to investigate whether the PLIC damage quantified by non-contrast computed tomography (NCCT) is associated with clinical outcomes after basal ganglia intracerebral hemorrhage (BG-ICH). This study retrospectively included 146 BG-ICH patients from the Department of Neurosurgery at the Second Affiliated Hospital of Chongqing Medical University. The damage to the PLIC was quantified using Tangency X measured by NCCT. The importance of features is determined using the Boruta algorithm and Least Absolute Shrinkage and Selection Operator (LASSO) regression. Multivariate logistic regression models were established to examine the impact of PLIC damage on outcomes. Restricted Cubic Splines (RCS) were used to explore potential nonlinear relationships, and Receiver Operating Characteristic (ROC) curves were used to compare the predictive performance of Tangency X with other scoring systems for 6-month neurological outcomes (poor outcomes [mRS: 3-6]). In the multivariate logistic regression adjusting for all covariates, Tangency X was independently associated with an increased risk of poor outcomes (OR = 1.32, 95% CI: 1.17-1.52) in BG-ICH patients. There is a nonlinear relationship between Tangency X and poor outcomes. Specifically, the risk of poor outcomes increases by 1.29 times (OR = 1.29, 95% CI: 1.09-1.67) for each additional 1 mm increase in Tangency X beyond 4 mm. We next observed that the AUC for Tangency X in predicting poor outcomes is 0.8511. The extent of PLIC damage measured by NCCT may represent a promising predictor of poor outcomes after BG-ICH.

Mapping individual cortico-basal ganglia-thalamo-cortical circuits integrating structural and functional connectome: implications for upper limb motor impairment poststroke.

This study investigated alterations in functional connectivity (FC) within cortico-basal ganglia-thalamo-cortical (CBTC) circuits and identified critical connections influencing poststroke motor recovery, offering insights into optimizing brain modulation strategies to address the limitations of traditional single-target stimulation. We delineated individual-specific parallel loops of CBTC through probabilistic tracking and voxel connectivity profiles-based segmentation and calculated FC values in poststroke patients and healthy controls, comparing with conventional atlas-based FC calculation. Support vector machine (SVM) analysis distinguished poststroke patients from controls. Connectome-based predictive modeling (CPM) used FC values within CBTC circuits to predict upper limb motor function. Poststroke patients exhibited decreased ipsilesional connectivity within the individual-specific CBTC circuits. SVM analysis achieved 82.8% accuracy, 76.6% sensitivity, and 89.1% specificity using individual-specific parallel loops. Additionally, CPM featuring positive connections/all connections significantly predicted Fugl-Meyer assessment of upper extremity scores. There were no significant differences in the group comparisons of conventional atlas-based FC values, and the FC values resulted in SVM accuracy of 75.0%, sensitivity of 67.2%, and specificity of 82.8%, with no significant CPM capability. Individual-specific parallel loops show superior predictive power for assessing upper limb motor function in poststroke patients. Precise mapping of the disease-related circuits is essential for understanding poststroke brain reorganization.

Low-beta versus high-beta band cortico-subcortical coherence in movement inhibition and expectation.

Beta band oscillations in the sensorimotor cortex and subcortical structures, such as the subthalamic nucleus (STN) and internal pallidum (GPi), are closely linked to motor control. Recent research suggests that low-beta (14.5-23.5 Hz) and high-beta (23.5-35 Hz) cortico-STN coherence arise through distinct networks, possibly reflecting indirect and hyperdirect pathways. In this study, we sought to probe whether low- and high-beta coherence also exhibit different functional roles in facilitating and inhibiting movement. Twenty patients with Parkinson's disease who had deep brain stimulation electrodes implanted in either STN or GPi performed a classical go/nogo task while undergoing simultaneous magnetoencephalography and local field potentials recordings. Subjects' expectations were manipulated by presenting go- and nogo-trials with varying probabilities. We identified a lateral source in the sensorimotor cortex for low-beta coherence, as well as a medial source near the supplementary motor area for high-beta coherence. Task-related coherence time courses for these two sources revealed that low-beta coherence was more strongly implicated than high-beta coherence in the performance of go-trials. Accordingly, average pre-stimulus low-beta but not high-beta coherence or spectral power correlated with overall reaction time across subjects. High-beta coherence during unexpected nogo-trials was higher compared to expected nogo-trials at a relatively long latency of 3 s after stimulus presentation. Neither low- nor high-beta coherence showed a significant correlation with patients' symptom severity at baseline assessment. While low-beta cortico-subcortical coherence appears to be related to motor output, the role of high-beta coherence requires further investigation.

Differential impact of optogenetic stimulation of direct and indirect pathways from dorsolateral and dorsomedial striatum on motor symptoms in Huntington's disease mice.

The alterations in the basal ganglia circuitry are core pathological hallmark in Huntington's Disease (HD) and traditionally linked to its sever motor symptoms. Recently it was shown that optogenetic stimulation of cortical afferences to the striatum is able to reverse motor symptoms in HD mice. However, the specific contribution of the direct and indirect striatal output pathways from the dorsolateral (DLS) and dorsomedial striatum (DMS) to the motor phenotype is still not clear. Here, we aim to uncover the contributions of these striatal subcircuits to motor control in wild type (WT) and HD mice by using the symptomatic R6/1 mice. We systematically evaluated locomotion, exploratory behavior, and motor learning effects of the selective optogenetic stimulation of D1 or A2A expressing neurons (direct and indirect pathway, respectively), in DLS or DMS. Bilateral optogenetic stimulation of the direct pathway from DLS and the indirect pathway from DMS resulted in subtle locomotor enhancements, while unaltering exploratory behavior. Additionally, bilateral stimulation of the indirect pathway from the DLS improved performance in the accelerated rotarod task, suggesting a role in motor learning. In contrast, in HD mice, stimulation of these pathways did not modulate any of these behaviors. Overall, this study highlights that selective stimulation of direct and indirect pathways from DLS and DMS have subtle impact in locomotion, exploratory activity nor motor learning. The lack of responses in HD mice also suggests that strategies involving cortico-striatal circuits rather than striatal output circuits might be a better strategy for managing motor symptoms in movement disorders.

Neural representations of beat and rhythm in motor and association regions.

Humans perceive a pulse, or beat, underlying musical rhythm. Beat strength correlates with activity in the basal ganglia and supplementary motor area, suggesting these regions support beat perception. However, the basal ganglia and supplementary motor area are part of a general rhythm and timing network (regardless of the beat) and may also represent basic rhythmic features (e.g. tempo, number of onsets). To characterize the encoding of beat-related and other basic rhythmic features, we used representational similarity analysis. During functional magnetic resonance imaging, participants heard 12 rhythms-4 strong-beat, 4 weak-beat, and 4 nonbeat. Multi-voxel activity patterns for each rhythm were tested to determine which brain areas were beat-sensitive: those in which activity patterns showed greater dissimilarities between rhythms of different beat strength than between rhythms of similar beat strength. Indeed, putamen and supplementary motor area activity patterns were significantly dissimilar for strong-beat and nonbeat conditions. Next, we tested whether basic rhythmic features or models of beat strength (counterevidence scores) predicted activity patterns. We found again that activity pattern dissimilarity in supplementary motor area and putamen correlated with beat strength models, not basic features. Beat strength models also correlated with activity pattern dissimilarities in the inferior frontal gyrus and inferior parietal lobe, though these regions encoded beat and rhythm simultaneously and were not driven by beat alone.

A comparative study of interhemispheric functional connectivity in patients with basal ganglia ischemic stroke.

Background: Voxel-mirrored homotopic connectivity (VMHC) is utilized to assess the functional connectivity of neural networks by quantifying the similarity between corresponding regions in the bilateral hemispheres of the brain. The exploration of VMHC abnormalities in basal ganglia ischemic stroke (BGIS) patients across different cerebral hemispheres has been limited. This study seeks to establish a foundation for understanding the functional connectivity status of both brain hemispheres in BGIS patients through the utilization of VMHC analysis utilizing resting-state functional magnetic resonance imaging (rs-fMRI). Methods: This study examined a total of 38 patients with left basal ganglia ischemic stroke (LBGIS), 44 patients with right basal ganglia ischemic stroke (RBGIS), and 41 individuals in a healthy control (HC) group. Rs-fMRI studies were performed on these patients, and the pre-processed rs-fMRI data were analyzed using VMHC method. Subsequently, the VMHC values were compared between three groups using a one-way ANOVA and post hoc analysis. Correlation analysis with clinical scales was also conducted. Results: The results indicated that compared to the HC group, significant differences were detected in postcentral gyrus, extending to precentral gyrus in both BGIS groups. Post hoc analysis showed that in the pairwise ROI-based comparison, individuals with LBGIS and RBGIS exhibited reduced VMHC values compared to HC groups. There was no significant difference between the LBGIS and RBGIS groups. In the LBGIS group, the VMHC value showed a negative correlation with NIHSS and a positive correlation with BI. Conclusion: The analysis of VMHC in rs-fMRI revealed a pattern of brain functional remodeling in patients with unilateral BGIS, marked by reduced synchronization and coordination between hemispheres. This may contribute to the understanding of the neurological mechanisms underlying motor dysfunction in these patients.

Effects of Mixed Metal Exposure on MRI Metrics in Basal Ganglia.

Welding fumes contain various metals. Past studies, however, mainly focused on Manganese (Mn)-related neurotoxicity. This study investigated welding-related mixed metal exposure effects on MRI metrics in the basal ganglia (BG) and their dose-response relationship. Subjects with (N = 23) and without (N = 24) a welding exposure history were examined. Metal exposure was estimated with exposure history questionnaire and whole blood metal levels. T1 (weighted-intensity and relaxation time; estimates of brain Mn accumulation), diffusion tensor imaging [Axial (AD), mean (MD), radial diffusivity (RD), and fractional anisotropy (FA); estimates of microstructural differences] metrics in BG [caudate nucleus, putamen, and globus pallidus (GP)] and voxel-based morphometry (for volume) were examined and related with metal exposure measures. Compared to controls, welders showed higher GP R1 (1/T1; p = 0.034) but no differences in blood metal and T1-weighted (T1W) values in any ROIs (p's > 0.120). They also had higher AD and MD values in the GP (p's < 0.033) but lower FA values in the putamen (p = 0.039) with no morphologic differences. In welders, higher blood Mn and Vanadium (V) levels predicted higher BG R1 and T1W values (p's < 0.015). There also were significant overall metal mixture effects on GP T1W and R1 values. Moreover, GP AD and MD values showed non-linear associations with BG T1W values: They increased with increasing T1W values only above certain threshold of T1 values. The current findings suggest that Mn and V individually but also metal mixtures jointly predict GP T1 signals that may in turn contribute to altered DTI metrics in the BG after certain exposure threshold levels.

Cryptogenic New-onset Refractory Status Epilepticus with Hyperintensity of T1-weighted Magnetic Resonance Imaging in the Bilateral Basal Ganglia: An Autopsy Report.

We present a 76-year-old man with cryptogenic new-onset refractory status epilepticus (C-NORSE) with an initial abnormal signal in the nucleus accumbens and a remarkable hyperintense signal on T1-weighted magnetic resonance imaging in the bilateral basal ganglia (BG). His status epilepticus did not respond to most anti-epileptic therapies or immunotherapies, and he died of sepsis. An autopsy revealed severe neuronal loss and hypertrophic astrocytes in the BG and limbic system, with no signs of inflammation or malignancy. This case suggests that lesions in the BG may reflect secondary degeneration and predict poor outcomes in C-NORSE.

The subthalamic nucleus contributes causally to perceptual decision-making in monkeys.

The subthalamic nucleus (STN) plays critical roles in the motor and cognitive function of the basal ganglia (BG), but the exact nature of these roles is not fully understood, especially in the context of decision-making based on uncertain evidence. Guided by theoretical predictions of specific STN contributions, we used single-unit recording and electrical microstimulation in the STN of healthy monkeys to assess its causal, computational roles in visual-saccadic decisions based on noisy evidence. The recordings identified subpopulations of STN neurons with distinct task-related activity patterns that related to different theoretically predicted functions. Microstimulation caused changes in behavioral choices and response times that reflected multiple contributions to an 'accumulate-to-bound'-like decision process, including modulation of decision bounds and evidence accumulation, and to non-perceptual processes. These results provide new insights into the multiple ways that the STN can support higher brain function.

3D Slicer combined with neuroendoscopic surgery for the treatment of basal ganglia hemorrhage after cranioplasty: A case report and literature review.

The minimally invasive surgery through transcranial endoscopic keyhole approach has become the main surgical method for treating cerebral hemorrhage. This method has the advantages of small trauma, short surgical time, low bleeding volume, and fast postoperative recovery. However, this method is not suitable for cases where cerebral hemorrhage occurs again after skull repair surgery. Our team used 3D Slicer reconstruction combined with virtual reality technology to find a suitable keyhole surgical approach and successfully completed a neuroendoscopic removal of basal ganglia hemorrhage through the eyebrow arch keyhole approach in a case of recurrent cerebral hemorrhage after cranioplasty.

Synaptic integration of somatosensory and motor cortical inputs onto spiny projection neurons of mice caudoputamen.

The basal ganglia play pivotal roles in motor control and cognitive functioning. These nuclei are embedded in an anatomical loop: cortex to basal ganglia to thalamus back to cortex. We focus here on an essential synapse for descending control, from cortical layer 5 (L5) onto the GABAergic spiny projection neurons (SPNs) of the caudoputamen (CP). We employed genetic labeling to distinguish L5 neurons from somatosensory (S1) and motor (M1) cortices in large volume serial electron microscopy and electrophysiology datasets to better detail these inputs. First, M1 and S1 synapses showed a strong preference to innervate the spines of SPNs and rarely contacted aspiny cells, which are likely to be interneurons. Second, L5 inputs commonly converge from both areas onto single SPNs. Third, compared to unlabeled terminals in CP, those labeled from M1 and S1 show ultrastructural hallmarks of strong driver synapses: They innervate larger spines that were more likely to contain a spine apparatus, more often had embedded mitochondria, and more often contacted multiple targets. Finally, these inputs also demonstrated driver-like functional properties: SPNs responded to optogenetic activation from S1 and M1 with large EPSP/Cs that depressed and were dependent on ionotropic but not metabotropic receptors. Together, our findings suggest that individual SPNs integrate driver input from multiple cortical areas with implications for how the basal ganglia relay cortical input to provide inhibitory innervation of motor thalamus.

Unraveling Diabetic Striatopathy: Clinical and Imaging Perspectives.

Diabetic striatopathy (DS) is an acute hyperkinetic movement disorder arising from non-ketotic hyperglycemia. This condition predominantly affects females and is more common in the elderly, highlighting the interplay between diabetes, striatal pathology, and neurological movement disorders. DS is characterized by involuntary movements, such as hemichorea or hemiballism, and distinctive neuroimaging findings that can be mistaken for more common cerebrovascular events. In this case report, we describe a 67-year-old female with a history of poorly controlled type 2 diabetes mellitus who presented with the sudden onset of involuntary movements affecting her left upper and lower limbs. Clinical examination and laboratory investigations revealed hyperglycemia without ketosis. Neuroimaging via computed tomography (CT) of the brain identified a hyper density in the right lentiform nucleus, consistent with DS. The patient was treated with vesicular monoamine transporter 2 (VMAT) inhibitors, oral hypoglycemic agents, and insulin, resulting in marked symptom improvement over 10 days. This case underscores the importance of recognizing DS as a differential diagnosis in patients with hyperkinetic movement disorders and hyperglycemia. Proper diagnosis and management, including stringent glycemic control, are crucial for symptom resolution.

Central nervous system involvement in Erdheim-Chester disease: a magnetic resonance imaging study.

PURPOSE: To characterize brain MR imaging findings in a cohort of 58 patients with ECD and to evaluate relationship between these findings and the BRAFV600E pathogenic variant. METHODS: ECD patients of any gender and ethnicity, aged 2-80 years, with biopsy-confirmed ECD were eligible to enroll in this study. Two radiologists experienced in evaluating ECD CNS disease activity reviewed MRI studies. Any disagreements were resolved by a third reader. Frequencies of observed lesions were reported. The association between the distribution of CNS lesions and the BRAFV600Epathogenic variant was evaluated using Fisher's exact test and odd ratio. RESULTS: The brain MRI of all 58 patients with ECD revealed some form of CNS lesions, most likely due to ECD. Cortical lesions were noted in 27/58 (46.6 %) patients, cerebellar lesions in 15/58 (25.9 %) patients, brain stem lesions in 17/58 cases (29.3 %), and pituitary lesions in 10/58 (17.2 %) patients. Premature cortical atrophy was observed in 8/58 (13.8 %) patients. BRAFV600E pathogenic variant was significantly associated with cerebellar lesions (p = 0.016) and bilateral brain stem lesions (p = 0.043). A trend toward significance was noted for cerebral atrophy (p = 0.053). CONCLUSION: The study provides valuable insights into the brain MRI findings in ECD and their association with the BRAFV600E pathogenic variant, particularly its association in cases with bilateral lesions. We are expanding our understanding of how ECD affects cerebral structures. Knowledge of MRI CNS lesion patterns and their association with mutations such as the BRAF variant is helpful for both prognosis and clinical management.

Adaptive circuits for action and value information in rodent operant learning.

Operant learning is a behavioral paradigm where animals learn to associate their actions with consequences, adapting their behavior accordingly. This review delves into the neural circuits that underpin operant learning in rodents, emphasizing the dynamic interplay between neural pathways, synaptic plasticity, and gene expression changes. We explore the cortico-basal ganglia circuits, highlighting the pivotal role of dopamine in modulating these pathways to reinforce behaviors that yield positive outcomes. We include insights from recent studies, which reveals the intricate roles of midbrain dopamine neurons in integrating action initiation and reward feedback, thereby enhancing movement-related activities in the dorsal striatum. Additionally, we discuss the molecular diversity of striatal neurons and their specific roles in reinforcement learning. The review also covers advances in transcriptome analysis techniques, such as single-cell RNA sequencing, which have provided deeper insights into the gene expression profiles associated with different neuronal populations during operant learning.

Subcortical Aphasia: An Update.

PURPOSE OF REVIEW: This review aims to rediscuss the leading theories concerning the role of basal ganglia and the thalamus in the genesis of aphasic symptoms in the absence of gross anatomical lesions in cortical language areas as assessed by conventional neuroimaging studies. RECENT FINDINGS: New concepts in language processing and modern neuroimaging techniques have enabled some progress in resolving the impasse between the current dominant theories: (a) direct and specific linguistic processing and (b) subcortical structures as processing relays in domain-general functions. Of particular interest are studies of connectivity based on functional magnetic resonance imaging (MRI) and tractography that highlight the impact of white matter pathway lesions on aphasia development and recovery. Connectivity studies have put into evidence the central role of the arcuate fasciculus (AF), inferior frontal occipital fasciculus (IFOF), and uncinate fasciculus (UF) in the genesis of aphasia. Regarding the thalamus, its involvement in lexical-semantic processing through modulation of the frontal cortex is becoming increasingly apparent.

Children's exposure to chemical contaminants: Demographic disparities and associations with the developing basal ganglia.

Children are regularly exposed to chemical contaminants that may influence brain development. However, relatively little is known about how these contaminants impact the developing human brain. Here, we combined silicone wristband exposure assessments with neuroimaging for the first time to examine how chemical contaminant mixtures are associated with the developing basal ganglia-a brain region key for the healthy development of emotion, reward, and motor processing, and which may be particularly susceptible to contaminant harm. Further, we examined demographic disparities in exposures to clarify which children were at highest risk for any contaminant-associated neurobiological changes. Participants included 62 community children (average age 7.00 years, 53% female, 66% White) who underwent structural neuroimaging to provide data on their basal ganglia structure and wore a silicone wristband for seven days to track their chemical contaminant exposure. 45 chemical contaminants-including phthalates and their alternatives, brominated flame retardants, organophosphate esters, pesticides, polycyclic aromatic hydrocarbons, and polychlorinated biphenyls-were detected in over 75% of wristbands. Notable demographic disparities in exposure were present, such that Non-White and lower-income children were more exposed to several contaminants. Exposure to chemical contaminant mixtures was not associated with overall basal ganglia volume; however, two organophosphate esters (2IPPDPP and 4IPPDPP) were both associated with a larger globus pallidus, a basal ganglia sub-region. Results highlight demographic disparities in exposure and suggest possible risks to a brain region key for healthy emotional development.

Insights into the interaction between time and reward prediction on the activity of striatal tonically active neurons: A pilot study in rhesus monkeys.

Prior studies have documented the role of the striatum and its dopaminergic input in time processing, but the contribution of local striatal cholinergic innervation has not been specifically investigated. To address this issue, we recorded the activity of tonically active neurons (TANs), thought to be cholinergic interneurons in the striatum, in two male macaques performing self-initiated movements after specified intervals in the seconds range have elapsed. The behavioral data showed that movement timing was adjusted according to the temporal requirements. About one-third of all recorded TANs displayed brief depressions in firing in response to the cue that indicates the interval duration, and the strength of these modulations was, in some instances, related to the timing of movement. The rewarding outcome of actions also impacted TAN activity, as reflected by stronger responses to the cue paralleled by weaker responses to reward when monkeys performed correctly timed movements over consecutive trials. It therefore appears that TAN responses may act as a start signal for keeping track of time and reward prediction could be incorporated in this signaling function. We conclude that the role of the striatal cholinergic TAN system in time processing is embedded in predicting rewarding outcomes during timing behavior.