Globus Pallidus Research Articles

Projections between the globus pallidus externa and cortex span motor and non-motor regions.

The globus pallidus externa (GPe) is a heterogenous nucleus of the basal ganglia, with intricate connections to other basal ganglia nuclei, as well as direct connections to the cortex. The anatomic, molecular and electrophysiologic properties of cortex-projecting pallidocortical neurons are not well characterized. Here we show that pallidocortical neurons project to diverse motor and non-motor cortical regions, are organized topographically in the GPe, and segregate into two distinct electrophysiological and molecular phenotypes. In addition, we find that the GPe receives direct synaptic input back from deep layers of diverse motor and non-motor cortical regions, some of which form reciprocal connections onto pallidocortical neurons. These results demonstrate the existence of a fast, closed-loop circuit between the GPe and the cortex which is ideally positioned to integrate information about behavioral goals, internal states, and environmental cues to rapidly modulate behavior.

Neuroimaging Correlates with Clinical Severity in Wilson Disease: A Multiparametric Quantitative Brain MRI.

Previous studies have reported metal accumulation and microstructure changes in deep gray nuclei (DGN) in Wilson disease (WD). However, there are limited studies that investigate whether there is metal accumulation and microstructure changes in DGN of patients with WD with normal-appearing routine MRI. This study aimed to evaluate multiparametric changes in DGN of WD and whether the findings correlate with clinical severity in patients with WD. The study enrolled 28 patients with WD (19 with neurologic symptoms) and 25 controls. Fractional anisotropy (FA), mean diffusivity (MD), and magnetic susceptibility in globus pallidus, pontine tegmentum, dentate nucleus, red nucleus, head of caudate nucleus, putamen, substantia nigra, and thalamus were extracted. Correlations between imaging data and the Unified Wilson's Disease Rating Scale (UWDRS) neurologic subitems were explored. FA, MD, and susceptibility values were higher in multiple DGN of patients with WD than controls (P < .05). Patients with WD without abnormal signals in DGN on routine MRI also had higher FA, MD, and susceptibility values than controls (P < .017). We found that UWDRS neurologic subscores correlated with FA and susceptibility values of DGN (P < .05). In addition, we also found that FA and susceptibility values in specific structures correlated with specific neurologic symptoms of WD (ie, tremor, parkinsonism, dysarthria, dystonia, and ataxia) (P < .05). Patients with WD have increased FA, MD, and susceptibility values even before the lesion is morphologically apparent on routine MRI. The increased FA and susceptibility values correlate with clinical severity of WD.

GPe Projections to the Retrorubral Field Give Rise to Diverging GABAergic and DAergic Circuits.

The external segment of the globus pallidus (GPe) is involved in the modulation of motor output and limbic components of behavior. The circuitry by which the GPe contributes to limbic components of behavior remains unknown. While many investigations have focused on the local circuitry within the basal ganglia, numerous GPe projections to target regions outside of the basal ganglia including the midbrain, thalamus, and cortex exist and remain largely unexplored. Here, by anatomical and electrophysiological means we investigate the projections of the GPe to the Retrorubral Field (RRF), a dopaminergic nucleus in the caudal midbrain, in both male and female mice. We find that the GPe targets both GABAergic and DAergic neurons in the RRF (RRFDA and RRFGABA). Viral-assisted circuit mapping to trace the cell-type specific projection patterns of RRFDA and RRFGABA populations revealed diverging pathways. The connectivity of GPe-recipient RRFDA neurons followed the traditional medial forebrain bundle path, innervating the ventral striatum and to a lesser extent the dorsal striatum. GPe-recipient RRFGABA neurons, on the other hand, displayed broad projections targeting numerous brain regions involved in limbic function including the parabrachial nucleus, amygdala, and hypothalamus. These contrasting projection profiles reveal multiple nodes by which the GPe is disynaptically connected to the limbic system, representing novel access points for the GPe to modulate limbic components of behavior.Significance Statement Progress in our understanding of GPe composition, circuits, and functions has allowed for a greater appreciation of the role of the GPe in shaping behavior. Here, we elaborate on the connectivity of the GPe with the RRF, the third-largest dopaminergic nucleus of the ventral midbrain. We reveal the targeting of both RRFDA and RRFGABA neurons by the GPe and demonstrate the vast non-overlapping projection profiles of RRFDA and RRFGABA Via the multi-level limbic connectivity of the RRF, these results add a novel branch of circuitry to the GPe, which may represent the foundation for some of its non-motor functions.

Restoring Compromised Cl- in D2 Neurons of a HD Mouse Model Rescues Motor Disability.

Huntington's disease (HD) is a progressive neurodegenerative disorder with no cure, characterized by significant neurodegeneration of striatal GABAergic medium spiny neurons (MSNs). Early stages of the disease are characterized by the loss of dopamine 2 receptor-expressing MSNs (D2 MSNs) followed by degeneration of dopamine 1 receptor-expressing MSNs (D1 MSNs), leading to aberrant basal ganglia signaling. While the early degeneration of D2 MSNs and impaired GABAergic transmission are well-documented, potassium chloride cotransporter 2 (KCC2), a key regulator of intracellular chloride (Cl-), and therefore GABAergic signaling, has not been characterized in D1 and D2 MSNs in HD. We aimed to investigate whether Cl- regulation was differentially altered in D1 and D2 MSNs and may contribute to the early degeneration of D2 MSNs in male and female symptomatic R6/2 mice. We used electrophysiology to record the reversal potential for GABAA receptors (EGABA), a read-out for the efficacy of Cl- regulation, in striatal D1 and D2 MSNs and their corresponding output structures. During the early symptomatic phase (P55-P65), Cl- impairments were observed in D2 MSNs in R6/2 mice, with no change in D1 MSNs. Cl- regulation was also dysfunctional in the globus pallidus externa, resulting in GABA-mediated excitation. When we overexpressed KCC2 in D2 MSNs using AAV-mediated delivery, we delayed the onset of motor impairments in R6/2 mice. We demonstrate that Cl- homeostasis is differentially altered in D1 and D2 MSNs and may contribute to the enhanced susceptibility of D2 MSNs during HD progression.Significance Statement Huntington's Disease is an inherited neurodegenerative disease caused by a repeat expansion in the Huntingtin gene and characterized by the sequential loss of dopamine 2 and dopamine 1 receptor-expressing medium spiny neurons (D2 and D1 MSNs) of the striatum. MSNs release GABA, which depends on proper Cl- regulation for inhibition. We asked whether Cl- homeostasis is differentially altered in D1 and D2 MSNs and their output structures, and whether this altered expression contributes to the pattern of degeneration between these two principal striatal cell types. Using electrophysiology, biochemistry, and fluorescence imaging, we determined that Cl- regulation was impaired in D2 MSNs in R6/2 mice, with no change in D1 MSNs. Cl- was also dysregulated in the globus pallidus externa resulting in excitatory GABA.

The External Globus Pallidus as the Hub of the Auditory Cortico-Basal Ganglia Loop.

The cortico-basal ganglia loop has traditionally been conceptualized as consisting of three distinct information networks: motor, limbic, and associative. However, this three-loop concept is insufficient to comprehensively explain the diverse functions of the cortico-basal ganglia system, as emerging evidence suggests its involvement in sensory processing, including the auditory systems. In the present study, we demonstrate the auditory cortico-basal ganglia loop by using transgenic mice and viral-assisted labelings. The caudal part of the external globus pallidus (GPe) emerged as a major output nucleus of the auditory cortico-basal ganglia loop with the cortico-striato-pallidal projections as its input pathway and pallido-cortical and pallido-thalamo-cortical projections as its output pathway. GABAergic neurons in the caudal GPe dominantly innervated the nonlemniscal auditory pathway. They also projected to various regions, including the substantia nigra pars lateralis, cuneiform nucleus, and periaqueductal gray. Considering the functions associated with these GPe-projecting regions, auditory cortico-basal ganglia circuits may play a pivotal role in eliciting defensive behaviors against acoustic stimuli.

Modeling and Optimizing Deep Brain Stimulation to Enhance Gait in Parkinson's Disease: Personalized Treatment with Neurophysiological Insights.

Although high-frequency deep brain stimulation (DBS) is effective at relieving many motor symptoms of Parkinson's disease (PD), its effects on gait can be variable and unpredictable. This is due to 1) a lack of standardized and robust metrics for gait assessment in PD patients, 2) the challenges of performing a thorough evaluation of all the stimulation parameters space that can alter gait, and 3) a lack of understanding for impacts of stimulation on the neurophysiological signatures of walking. In this study, our goal was to develop a data-driven approach to identify optimal, personalized DBS stimulation parameters to improve gait in PD patients and identify the neurophysiological signature of improved gait. Local field potentials from the globus pallidus and electrocorticography from the motor cortex of three PD patients were recorded using an implanted bidirectional neural stimulator during overground walking. A walking performance index (WPI) was developed to assess gait metrics with high reliability. DBS frequency, amplitude, and pulse width on the "clinically-optimized" stimulation contact were then systemically changed to study their impacts on gait metrics and underlying neural dynamics. We developed a Gaussian Process Regressor (GPR) model to map the relationship between DBS settings and the WPI. Using this model, we identified and validated personalized DBS settings that significantly improved gait metrics. Linear mixed models were employed to identify neural spectral features associated with enhanced walking performance. We demonstrated that improved walking performance was linked to the modulation of neural activity in specific frequency bands, with reduced beta band power in the pallidum and increased alpha band pallidal-motor cortex coherence synchronization during key moments of the gait cycle. Integrating WPI and GPR to optimize DBS parameters underscores the importance of developing and understanding personalized, data-driven interventions for gait improvement in PD.

An FMRI Meta-Analysis of Interoception in Eating Disorders

Eating Disorders (EDs) are associated with disturbed interoception – the sense of the internal condition of the body. Disturbances in interoception across senses have not yet been comprehensively examined in EDs. To do so, we employed an innovative Bayesian author-topic model approach to fMRI meta-analyses that pools together neural deficits across interoceptive senses and task types in participants with and recovered from EDs. Following PRISMA guidelines, our results combine activation patterns from 1,341 initially screened studies and data from 25 manuscripts that met study criteria that compare 463 patients with EDs (current or recovered) to 450 healthy control participants (HC). Altered brain activity was found within vision/sensory processing (precuneus), taste/self-referential processing (claustrum/posterior insula) and reward/set-shifting (global pallidus, medial frontal gyrus, anterior cingulate, precentral gyrus and parietal lobe) components in EDs compared to HC. Our results reveal separate components for bottom-up exteroceptive and interoceptive processing centering around the precuneus and claustrum/insula and also reward processing/set-shifting deficits. Thus, bottom-up sensory and reward processing are key deficits in EDs during ill and recovered states.

Pathological study of progressive supranuclear palsy the cases with mutations in Bassoon.

Clinical diagnosis of progressive supranuclear palsy (PSP) is difficult due to various phenotypes. Neuropathologically, PSP is defined by neuronal loss in the basal ganglia and brainstem with widespread occurrence of neurofibrillary tangles (NFTs) and accumulation of phosphorylated tau protein in neurons and glial cells in the brain. We previously identified the point mutation p.Pro3866Ala in the Bassoon (BSN) gene in a Japanese family with PSP-like syndrome. We newly detected BSN mutations in two autopsied PSP cases carrying p.Thr2542Met and p.Glu2759Gly, respectively. The case with p.Thr2542Met mutation showed neurological symptoms including behavioral abnormalities, cognitive dysfunction, and parkinsonism. Brain magnetic resonance imaging (MRI) showed atrophy of the midbrain tegmentum and hippocampus. Pathologically, moderate to severe loss of neurons with gliosis was also found in the substantia nigra, and there was an almost complete loss of neurons with gliosis in the transitional zone of the cornu ammonis (CA) 1 region to the subiculum. NFTs were observed in the globus pallidus, subthalamic nucleus, substantia nigra, and CA1. 4R tau-dominant tauopathy was detected. The case with p.Glu2759Gly mutation showed neurological symptoms, including right-dominant motor impairment, right limping gait, postural instability, and cognitive dysfunction. Brain MRI showed mild atrophy of the midbrain tegmentum and left-dominant parietal lobe atrophy. Pathologically, NFTs were detected in the globus pallidus, subthalamic nucleus, substantia nigra, thalamus, putamen, and brainstem tegmentum. Most neurons were immunopositive for four-repeat tau, whereas only a few of them harbored three-repeat tau-positive NFTs in the hippocampus. We showed the results of a pathological study of PSP cases with BSN mutations; these were two new cases. The clinical phenotypes were similar to the first case in the point of neurological symptoms. Accumulation of four-repeat tau was dominant. Further autopsies of BSN mutation cases and further elucidation of the molecular biological mechanism are desirable.

Modified salpingopharyngeus myomucosal flap: a novel technique for skull base reconstruction.

Advancements in endoscopic skull base surgery have enabled complex tumor resections, necessitating a variety of reliable reconstructive techniques to repair resultant defects. Vascularized flaps represent optimal options, but frequently used local pedicled intranasal flaps may be unavailable due to tumor invasion or prior surgery. This study applies a modification to the previously described salpingopharyngeus myomucosal flap (Dicle flap) with potential for its use in extensive endoscopic skull base surgery defect's repair. Cadaveric dissections (n = 5) were performed utilizing endoscopic visualization to access the skull base via endonasal and transoral routes. A superiorly based posterior pharyngeal myomucosal flap along the salpingopharyngeus muscle was elevated off the superior pharyngeal constrictors, preserving their vascular pedicles. This combined flap could be 180 degrees transposed to reconstruct clival defects up to the sella turcica. The modified salpingopharyngeus myomucosal flap (Modified Dicle flap) provided approximately 40 cm2 of robust vascularized tissue based on the ascending pharyngeal artery and random posterior pharyngeal vessels. It was sufficiently mobilized to cover extensive skull base defects in the craniocervical junction, sella turcica, and protecting the exposed internal carotid artery segments. The modified Dicle flap offers a viable reconstructive option for extensive endoscopic endonasal skull base defects when commonly utilized vascularized flaps are unavailable. Further research on clinical cases is warranted to investigate postoperative function and refine techniques to minimize donor site morbidity. Not applicable.

Deep brain stimulation for severe dystonia associated with Wilson disease: A prospective multicenter meta-analysis of an N-of-1 trial.

Disabling dystonia despite optimal medical treatment is common in Wilson disease (WD). No controlled study has evaluated the effect of deep brain stimulation (DBS) on dystonia related to WD. This study was undertaken to evaluate the efficacy of DBS on dystonia related to WD. A meta-analysis of an N-of-1 prospective, randomized, double-blind, multicenter DBS study was conducted at two French WD reference centers. Main inclusion criteria were patients with WD, stabilized for at least 6 months with significant disability due to dystonia despite optimized medical treatment. The subthalamic nucleus (STN) was targeted for bradykinetic patients with tonic dystonia, and the internal globus pallidus (GPi) was chosen for patients with hyperkinetic dystonia. Each patient underwent two periods of DBS "on" and two periods of DBS "off," each lasting 4 months. The order of stimulation conditions was randomized. The primary outcome was the change in the Canadian Occupational Performance Measure Performance (COPM-P) and Satisfaction scores after each 4-month period. Secondary outcomes were changes in the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) severity and disability scores and Unified Wilson's Disease Rating Scale (UWDRS) scores. Between 12 May 2016 and 7 October 2022, three patients were included. Two patients received bilateral GPi DBS, and one received bilateral STN DBS. There was no change of COPM-P (p = 0.956), BFMDRS, and UWDRS scores. No serious adverse events were reported. STN or GPi DBS are ineffective on dystonia related to WD.

Coronary Connector Facilitated Total Endoscopic Coronary Artery Bypass: An Ex Vivo Feasibility Study.

Totally endoscopic coronary artery bypass (TECAB) procedures pose significant challenges, motivating the development of Octocon, an automated endoscopic connector designed for coronary anastomoses in off-pump and endoscopic settings. This feasibility study aimed to assess Octocon's functionality and maneuverability in closed-chest conditions during robot-assisted TECAB simulations. The Octocon deployment comprises a 3-step procedure. Initially, delicate self-aligning microstapling technology is used to attach connector halves to individual blood vessels. Subsequently, the connector halves are joined to accomplish the anastomosis process. TECAB conditions were simulated using a dedicated box housing ex vivo porcine hearts. The study, conducted by 3 experienced surgeons, investigated the feasibility and standardization potential of a robot-assisted procedure employing Octocon. It evaluated maneuverability in closed-chest conditions and assessed the effectiveness of grafting internal mammary artery segments to different heart regions using single graft, jump graft, and Y-graft constructions. The robot-assisted procedure, using 4 standard instruments, successfully completed all 3 steps in 18 anastomotic procedures. In 96% of cases, the procedural steps were accomplished on the first attempt. The feasibility of constructing jump graft and Y-graft geometries on both anterior and posterior heart walls was demonstrated. Furthermore, experiences affirmed the device's endoscopic user-friendliness, ease of teachability, reproducibility, and potential to achieve expedient, leak-free anastomoses. This ex vivo study confirmed Octocon's potential suitability and functionality for TECAB. The device can create diverse grafting strategies and achieve wide-open vascular connections on various heart regions, highlighting its potential in advancing minimally invasive, robot-assisted coronary procedures. These promising results justify further exploration for integration into clinical practice.

Progressive postoperative atrophy of ipsilateral thalamus, putamen, and globus pallidus in patients with temporal lobe epilepsy: A volumetric analysis.

Cortical atrophy close to medial temporal structures has been described consistently in patients with temporal lobe epilepsy (TLE). Successful TLE surgery may have a neuroprotective effect preventing further atrophy of temporal and extratemporal cortex. However, the effects of epilepsy surgery on subcortical structures demand additional enlightenment. This work aimed to determine how epilepsy surgery affects volumes of subcortical structures in medically refractory temporal lobe epilepsy patients. We compared MRI volumes of subcortical structures in 62 patients with TLE (36 left, 26 right) before and after anterior temporal lobectomy with 38 TLE patients (20 left, 18 right) who were considered to be good surgical candidates and had at least two brain MRIs. There were no volume differences in subcortical structures on preoperative and initial MRIs of non-operated TLE patients. At baseline, the ipsilateral thalamus and putamen in TLE patients were marginally smaller than contralateral structures. Operated patients showed a significant postoperative volume reduction in ipsilateral thalamus, putamen, and globus pallidus. In contrast, there were no significant volumetric reductions in non-operated patients longitudinally. There were no volumetric changes associated with different surgical outcomes or different postoperative cognitive outcomes. Our study demonstrated postoperative volume loss of thalamus, putamen and globus pallidus ipsilaterally to the side of resection. Our findings suggest surgery-related changes, likely Wallerian degeneration within subcortical networks not related to seizure or cognitive outcome. We studied 100 patients with epilepsy, comparing those who had surgery to those who did not. After surgery, the thalamus, putamen and globus pallidus on the same side as the surgery shrank significantly, but not in non-surgery patients. This suggests surgery-related changes in deeper brain structures, unrelated to seizure freedom or cognitive outcomes. This research sheds additional light on the response of the subcortical structure to epilepsy surgery, highlighting potential areas for further study.

Tobacco Smoking Functional Networks: A Whole-Brain Connectome Analysis in 24,539 Individuals.

Nicotine addiction, a multifaceted neuropsychiatric disorder, profoundly impacts brain functions through interactions with neural pathways. Despite its significance, the impact of tobacco smoking on the whole-brain functional connectome remains largely unexplored. We conducted a whole-brain analysis on 24,539 adults aged 40 and above from the UK Biobank cohort. Subjects were categorized into individuals who use nicotine and who do not use nicotine based on current and chronic tobacco smoking information. Functional connectivity was assessed using resting-state functional magnetic resonance imaging (rfMRI). We employed a network analysis method to assess the systematic effects of tobacco smoking on brain connectome by identifying subnetworks that show nicotine-use-related differences. Our analyses revealed two nicotine-use-related subnetworks with distinct network structure (permutation p-value < 0.001). In the first network, there is a significant decrease in resting-state functional connectivity (rsFC) between the basal ganglia regions (e.g., nucleus accumbens) and 73% of the remaining brain regions, emphasizing the central hub role of basal ganglia in addictive smoking behaviors. Additionally, a data-driven subnetwork mainly involving regions from frontal and occipital lobes, showed reduced rsFC among individuals who use nicotine. The results suggest significant alterations in the communication and coordination among the basal ganglia and the broader network of brain regions. The observed changes in rsFC indicate a widespread disruption in the connectivity patterns associated with nicotine use. This study identifies rsFC subnetworks related to chronic nicotine use through whole-brain connectome analysis. The findings confirm that widespread alterations in rsFC are centered around hub nodes within the basal ganglia, including bilateral nucleus accumbens, putamen, caudate, and globus pallidus. In addition, our analysis found a clique-forming subnetwork vulnerable to tobacco smoking consisting of regions from the visual, dorsal/ventral attention, and frontoparietal networks.

Association between iron content in grey matter nuclei and functional outcome in patients with acute ischaemic stroke: A quantitative susceptibility mapping study.

This study aimed to investigate the association between iron content in grey matter (GM) nuclei and functional outcome in acute ischaemic stroke (AIS) patients utilizing quantitative susceptibility mapping. Forty AIS patients and 40 age-, sex- and education-matched healthy controls underwent quantitative susceptibility mapping to assess susceptibility values, which are positively correlated with iron content, in the caudate nucleus, putamen, globus pallidus, thalamus, red nucleus and substantia nigra. The nuclei on the contralateral side were measured in AIS patients to minimize confounding due to oedema or haemorrhage. Functional outcome was determined by the modified Rankin Scale (mRS) score at 3 months after stroke. Poor outcome was defined as mRS >2, whilst a good outcome was defined as ≤2. Susceptibility values were significantly higher in most contralateral GM nuclei in AIS patients than in the corresponding left or right nuclei in healthy controls. AIS patients with poor outcome showed significantly lower susceptibility value than those with good outcome in the contralateral caudate nucleus, but no significant differences were observed in other GM nuclei. Binary logistic regression analysis revealed a significant association between the susceptibility value of the contralateral caudate nucleus and poor outcome after adjustment for confounders (adjusted odds ratio 0.692, 95% confidence interval 0.486-0.986, p = 0.042). Receiver operating characteristic curve analysis showed an acceptable ability of the susceptibility value of the contralateral caudate nucleus to predict poor outcome (area under the curve 0.740, p = 0.013). Lower iron content in the contralateral caudate nucleus was associated with poor functional outcome in AIS patients.

An adaptive dynamic surface control strategy for suppressing pathological oscillations in a neural mass model

Pathological oscillations that have a frequency in the [Formula: see text] band are widely recognized to be involved in Parkinson’s disease. Now, we present an adaptive dynamic surface control strategy for suppressing pathological oscillations that exist in the Parkinsonian state. First, the interactions between the subthalamic nucleus and external globus pallidus are fully considered and establish a neural mass model of Parkinson’s disease. Next, by reasonable state transformation, suppressing pathological oscillations can be converted into a tracking control study of a pure-feedback nonlinear system. Moreover, the dynamic surface control technique adopted reduces the dimensionality of the neural network input and effectively eliminates the complexity explosion problem commonly associated with existing methods. By Lyapunov stability analysis, it can be obtained that all the signals of the resulting closed-loop system are bounded, and the tracking error converges to a small neighborhood of zero. Finally, the simulation results demonstrate the effectiveness of the designed control strategy. This work may provide an effective approach to closed-loop deep brain stimulation optimization for the alleviation of the Parkinsonian state.

Prospective Connectomic-Based Deep Brain Stimulation Programming for Parkinson's Disease.

Efficacy of deep brain stimulation (DBS) relies on accurate lead placement as well as optimization of the stimulation parameters. Although clinical software tools are now available, programming still largely relies on a monopolar review, a tedious process for both patients and programmers. This study investigates the safety and feasibility of prospective automated connectomic DBS programming (automated connectomic programming [ACP]), focusing on the recruitment of specific white matter pathways. After DBS implantation, a detailed connectomic DBS model in patient-specific space was developed for each study participant. A driving-force model was used to quantify pathway recruitment across 2400 different DBS settings. Optimization algorithms maximized recruitment of therapeutic pathways while minimizing recruitment of side-effect pathways. Thirteen subjects were enrolled in two study phases that compared DBS settings derived from ACP to standard clinical DBS settings. Nine patients underwent reprogramming with ACP (5 globus pallidus interna [GPi], 4 subthalamic nucleus [STN]). Four patients underwent initial programming with ACP (3 GPi, 1 STN). All patients tolerated ACP without persistent side effects. In the reprogramming cohort, 3 patients preferred their ACP program, and 1 patient felt it was comparable to their clinical program. Unified Parkinson's Disease Rating Scale, Part III, scores for the initial ACP cohort (3 GPi, 1 STN) improved by an average of 43.5% (40.4-52.6 ± 5.6%). ACP appeared clinically safe and feasible. It provided reasonable motor improvement, which can be further optimized with subsequent clinical adjustment. Additional investigation is required to refine the optimization algorithm and to quantify the clinical benefit of ACP in a larger cohort. © 2024 International Parkinson and Movement Disorder Society.

Genomic analysis of intracranial and subcortical brain volumes yields polygenic scores accounting for variation across ancestries.

Subcortical brain structures are involved in developmental, psychiatric and neurological disorders. Here we performed genome-wide association studies meta-analyses of intracranial and nine subcortical brain volumes (brainstem, caudate nucleus, putamen, hippocampus, globus pallidus, thalamus, nucleus accumbens, amygdala and the ventral diencephalon) in 74,898 participants of European ancestry. We identified 254 independent loci associated with these brain volumes, explaining up to 35% of phenotypic variance. We observed gene expression in specific neural cell types across differentiation time points, including genes involved in intracellular signaling and brain aging-related processes. Polygenic scores for brain volumes showed predictive ability when applied to individuals of diverse ancestries. We observed causal genetic effects of brain volumes with Parkinson's disease and attention-deficit/hyperactivity disorder. Findings implicate specific gene expression patterns in brain development and genetic variants in comorbid neuropsychiatric disorders, which could point to a brain substrate and region of action for risk genes implicated in brain diseases.

Treatment of Cerebral Vasospasm after Aneurysmal Subarachnoid Hemorrhage Using the Compliant Manually Adjustable Mesh Comaneci.

Background and purpose: Cerebral vasospasm (CV) following aneurysmal subarachnoid hemorrhage (aSAH) may lead to morbidity and mortality. Endovascular mechanical angioplasty may be performed if symptomatic CV is refractory to noninvasive medical management. Compliant and noncompliant balloons and manually adjustable mesh may be used in this indication. We describe our initial experience with the Comaneci (Rapid Medical, Yokneam, Israel) in cerebral vasospasm treatment following aSAH. Methods: All patients included in the prospective observational SAVEBRAIN PWI (NCT05276934 on clinicaltrial.gov) study who underwent cerebral angioplasty using the Comaneci device for the treatment of medically refractory and symptomatic CV after aSAH were identified. Patient demographic information, procedural details, and outcomes were obtained from electronic medical records. Results: Between February 2022 and June 2023, seven consecutive patients underwent CV treatment with the Comaneci. Angioplasty of 37 arterial segments (supraclinoid internal carotid artery, A1, A2, and A3 segments of the anterior cerebral artery and M1 and M2 segments of the middle cerebral artery) was attempted, and 35/37 (95%) were performed. The vessel diameter improved significantly following angioplasty (+64%), while brain hypoperfusion decreased (-45% of the mean T Max). There was no long-term clinical complication, and 6% per-procedural complications occurred. Conclusions: The Comaneci is effective in the treatment of cerebral vasospasm following aSAH, bringing a new device in the armamentarium of the neurointerventionalist to perform intracranial angioplasty.

The mediation effect of the inferior-parietal cortex and globus pallidus on the relationship between family conflict and major depressive disorder

ObjectiveFamily conflict is an important risk factor for major depressive disorder (MDD) and is associated with structural alterations in the brain. However, it is unclear whether structural alterations associated with family conflict would contribute to depression. This study aims to investigate the neuroimaging characteristics that connect family conflict with depression. MethodsThis study included 54 healthy controls and 53 antidepressant-free patients with MDD. Both groups completed the Beck Depression Inventory-II, the simplified Chinese version of the Family Environment Scale, and the Childhood Trauma Questionnaire. Structural Magnetic Resonance Imaging data was collected to measure cortical thickness and regional gray matter volumes. ResultsFamily conflict has a significant effect on depression diagnosis. Higher levels of family conflict were positively associated with symptoms of sadness, guilty feelings, and punishment feelings in patients, as well as with cortical thickness in the right inferior-parietal cluster and the volumes of the left globus pallidus in all participants. In the patient group, cortical thickness in the right inferior-parietal cluster and volume of the left globus pallidus were negatively related to symptoms of sadness and guilty feelings, respectively. The structural alteration in the right inferior-parietal cluster mediated the relationship of family conflict and sadness, whereas changes in the globus pallidus mediated the associations between family conflict and both depression and guilty feelings in patients. ConclusionFindings revealed the relationships between family conflict and depression, including both depression diagnosis and specific symptoms. Cortical thickness in the right inferior-parietal cortex and the volume of the left globus pallidus played mediating roles in these relationships, indicating the important contributions of these brain regions to the effect of family conflict on depression.

Correlation between iron deposition and cognitive function in mild to moderate Alzheimer's disease based on quantitative susceptibility mapping.

Alzheimer's disease (AD) is a complex neurodegenerative disorder characterized by progressively worsening cognitive decline and memory loss. Excessive iron accumulation produces severe cognitive impairment. However, there are no uniform conclusions about changes in brain iron content in AD. This study aimed to investigate the iron content of the deep brain nuclei in AD, and its correlation with cognitive function. Thirty-one patients with mild to moderate AD, 17 patients with mild cognitive impairment (MCI), and 20 age-, sex-, and education-matched healthy controls (HC) were collected. The QSM was used to quantify the magnetic susceptibility values of the caudate nucleus, putamen, globus pallidus, substantia nigra, red nucleus, and dentate nucleus, and to analyze the differences that existed between the three groups. As well as the correlation between the magnetic susceptibility values and cognitive function was calculated. The magnetic susceptibility values of bilateral globus pallidus, left putamen, and bilateral substantia nigra were significantly higher in AD patients than in HC, and the magnetic susceptibility values of the right globus pallidus were significantly higher in AD patients than in MCI (all p < 0.05). The magnetic susceptibility values of the left dentate nucleus in the AD group were negatively correlated with the writing function of the MMSE subitem (r = -0.42, p = 0.020), and the magnetic susceptibility values of the left caudate nucleus and right dentate nucleus were significantly and negatively correlated with the naming function and language function of the MoCA subitem, respectively (r = -0.43, p = 0.019; r = -0.36, p = 0.048). Magnetic susceptibility values based on QSM correlate with cognitive function are valuable in discriminating AD from MCI and AD from HC.