Globus Pallidus Research Articles

Validation of Tenths Stereotactic Coordinates Method Using Probabilistic Tractography of the Ansa Lenticularis in Parkinson's Disease Patients

To evaluate the accuracy of stereotactic coordinates to target the ansa lenticularis (AL) using 2 surgical planning methods, the conventional millimeter method (MM) and the normalized Tenths method (TM), assessed through individualized probabilistic tractography. Stereotactic targeting of the AL was assessed in 2 groups: 16 patients with Parkinson's disease and 16 healthy controls from Group 1, and 39 Parkinson's disease patients from Group 2. Structural and diffusion magnetic resonance imaging probabilistic tractography identified the AL based on the Schaltenbrand-Wahren Atlas. The MM defined stereotactic coordinates in millimeters, while the TM refined the planning by dividing the intercommissural line (AC-PC) distance into 10 equal parts, normalizing the "X," "Y," and "Z" coordinates for each patient. We subsequently compared the percentage of structural connectivity (%conn) of the AL with predefined regions of interest (ROIs), including the frontopontine-corticothalamic tracts, globus pallidus internus-ventral oral anterior, and ventral oral posterior, and quantified the streamlines in 142 brain hemispheres using the MM and TM coordinates. Despite anatomical variations in intercommissural (AC-PC) line lengths between both groups (22.5 ± 2.09mm and 24.4 ± 2.56mm, respectively; P= 0.002), as well as differences in magnetic resonance imaging acquisition parameters, we found that the TM significantly enhanced streamline identification and %conn compared to the MM. These enhancements were noted across ROIs: frontopontine-corticothalamic and globus pallidus internus-ventral oral anterior in both hemispheres, and globus pallidus internus-ventral oral posterior in the left (P < 0.001) and right hemispheres (P= 0.03). TM surpasses MM in identifying the structural connectivity between the AL and predefined ROIs, underscoring the advantages of coordinate normalization. However, variations in AC-PC line lengths and Euclidean distances between methods could lead to inaccuracies in the coordinate settings, potentially affecting the precision of structural connectivity and the efficacy of therapeutic outcomes.

Pure argyrophilic grain disease revisited: independent effects on limbic, neocortical, and striato-pallido-nigral degeneration and the development of dementia in a series with a low to moderate Braak stage

Agyrophilic grains (AGs) are age-related limbic-predominant lesions in which four-repeat tau is selectively accumulated. Because previous methodologically heterogeneous studies have demonstrated inconsistent findings on the relationship between AGs and dementia, whether AGs affect cognitive function remains unclear. To address this question, we first comprehensively evaluated the distribution and quantity of Gallyas-positive AGs and the severity of neuronal loss in the limbic, neocortical, and subcortical regions in 30 cases of pure argyrophilic grain disease (pAGD) in Braak stages I–IV and without other degenerative diseases, and 34 control cases that had only neurofibrillary tangles with Braak stages I–IV and no or minimal Aβ deposits. Then, we examined whether AGs have independent effects on neuronal loss and dementia by employing multivariate ordered logistic regression and binomial logistic regression. Of 30 pAGD cases, three were classified in diffuse form pAGD, which had evident neuronal loss not only in the limbic region but also in the neocortex and subcortical nuclei. In all 30 pAGD cases, neuronal loss developed first in the amygdala, followed by temporo-frontal cortex, hippocampal CA1, substantia nigra, and finally, the striatum and globus pallidus with the progression of Saito AG stage. In multivariate analyses of 30 pAGD and 34 control cases, the Saito AG stage affected neuronal loss in the amygdala, hippocampal CA1, temporo-frontal cortex, striatum, globus pallidus, and substantia nigra independent of the age, Braak stage, and limbic-predominant age-related TDP-43 encephalopathy (LATE-NC) stage. In multivariate analyses of 23 pAGD and 28 control cases that lacked two or more lacunae and/or one or more large infarctions, 100 or more AGs per × 400 visual field in the amygdala (OR 10.02, 95% CI 1.12–89.43) and hippocampal CA1 (OR 12.22, 95% CI 1.70–87.81), and the presence of AGs in the inferior temporal cortex (OR 8.18, 95% CI 1.03–65.13) affected dementia independent of age, moderate Braak stages (III–IV), and LATE-NC. Given these findings, the high density of limbic AGs and the increase of AGs in the inferior temporal gyrus may contribute to the occurrence of dementia through neuronal loss, at least in cases in a low to moderate Braak stage.

Number of serotonergic neurons in the subthalamic nucleus and globus pallidus internus could influence the effects of deep brain stimulation in Parkinson's disease.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) or globus pallidus internus (GPi) is a standard treatment for Parkinson's disease (PD), with both regions exhibiting similar treatment effectiveness. However, posttreatment neuropsychiatric side effects, such as severe depression, are common, primarily due to the loss of serotonergic cells. Identifying a region with fewer serotonergic neurons could potentially reduce these side effects. This study aimed to quantify the number of serotonergic neurons in the STN and GPi. Both regions were analyzed using hematoxylin and eosin staining and immunohistochemistry. The GPi exhibited a significantly lower number and H-score of serotonergic neurons than the STN. Within the STN, the number and H-score of serotonergic neurons were higher in the medial aspect than in the lateral aspect. Three different types of neurons, large and small, were observed. In STN, large neurons were concentrated in the center and small neurons in the periphery. This distribution was not observed in GPi. In addition, the concentration of the serotonergic neurons is less in GPi. These findings suggest that the GPi may be a safer target region, potentially reducing the incidence of post-DBS depression.

Examining Neural Correlates of Sexual Preferences between Persian Homo- and Heterosexual Males Using Psychological Assessments and Functional Magnetic Resonance Imaging in Specifying Cognitive Map: A Limited and Cross-sectional Study

AbstractAlthough the brain is an important part of a person's sexual life, little is known about the correlations between sexual response and brain activation. This study examines brain responses through clinical testing to reveal several brain structures whose activation is relevant to sexual arousal besides psychological testing according to the common traditional values and standards of Iranian society. Based on an initial self-report, 25 homosexual and 25 heterosexual males participated in this test to elucidate the identity and sexual trends via the Minnesota Multiphasic Personality Inventory (MMPI-2). Also, an fMRI technique—by presenting distinct homo- and heterosexual sex erotic pictures during the test—was employed in neural correlates of sexual arousal via blood oxygen level dependent (BOLD) signal measuring and Statistical Parametric Mapping analysis. In five selected homosexuals by the most appropriate MMPI test score, brain activities were significantly detected in the midbrain, amygdala, anterior cingulate gyrus, frontal cortex, orbitofrontal cortex, globus pallidus, thalamus, and putamen when the participant saw the erotic pictures during the test, which were responsive to sexual arousal. Also, bilateral caudate nucleus, left angular gyrus, and bilateral pallidum were activated but five selected heterosexuals showed no activation in these areas (p &lt; 0.001). Likewise, the MMPI method confirmed that homosexuality was relevant to diverse life positions, and biological and socioeconomic aspects. The maximum positive correlations were pairwise found in the parietal lobule by r = 0.61 (p &lt; 0.05) and in the frontal gyrus by r = 0.64 (p = 0.10), and the minimum negative correlations were in globus pallidus by r = − 0.18 (p &lt; 0.10) and r = − 0.16 (p &lt; 0.10) for homosexuals and heterosexuals, correspondingly. These results may be useful for understanding the different neural mechanisms of personality recognition and sexual orientation changes while incorporating the individual's history and experience simultaneously into the assessment.

Diagnostic and predictive power of plasma proteins in Alzheimer's disease: a cross-sectional and longitudinal study in China

Convenient and effective biomarkers are essential for the early diagnosis and treatment of Alzheimer’s disease (AD). In the cross-sectional study, 103 patients with AD, 82 patients with aMCI and 508 normal controls (NC) were enrolled. The single‐molecule array (Simoa) technique was used to assess the levels of plasma proteins, including NfL, T-tau, P-tau-181, Aβ40, Aβ42. Montreal Cognitive Assessment (MoCA) was used to assess the overall cognitive function of all subjects. Moreover, Amyloid PET and structural head MRI were also performed in a subset of the population. In the follow-up, the previous 508 normal older adults were followed up for two years, then COX regression analysis was used to investigate the association between baseline plasma proteins and future cognitive outcomes. NfL, T-tau, P-tau-181, Aβ40, Aβ42 and Aβ42/40 were altered in AD dementia, and NfL, Aβ42 and Aβ42/40 significantly outperformed all plasma proteins in differentiating AD dementia from NC, while NfL and Aβ42/40 could effectively distinguish between aMCI and NC. However, only plasma NfL was associated with future cognitive decline, and it was negatively correlated with MoCA (r = − 0.298, p < 0.001) and the volume of the left globus pallidus (r = − 0.278, p = 0.033). Plasma NfL can help distinguish between cognitively normal and cognitively impaired individuals (MCI/dementia) at the syndrome level. However, since we have not introduced other biomarkers for AD, such as PET CT or cerebrospinal fluid, and have not verified in other neurodegenerative diseases, whether plasma NFL can be used as a biomarker for AD needs to be further studied and explored.

Effect of Vericiguat Pre-treatment on Phenylephrine Constrictor Responses in Isolated Human Internal Mammary Artery Segments With/without Intact Endothelium

Effect of Vericiguat Pre-treatment on Phenylephrine Constrictor Responses in Isolated Human Internal Mammary Artery Segments With/without Intact Endothelium

Spatiotemporal Progression Patterns of Dopamine Availability and Deep Gray Matter Volume in Parkinson Disease-Related Cognitive Impairment.

Cognitive impairment is a frequent nonmotor symptom in patients with Parkinson disease (PD), and early cognitive decline is often attributed to dopaminergic system dysfunction. We aimed to explore spatiotemporal progression patterns of striatal dopamine availability and regional brain volume based on cognitive status among patients with PD. This retrospective, cross-sectional study included patients with newly diagnosed PD who were not taking medication for this condition who visited a university-affiliated hospital in Seoul between January 2018 and December 2020. Patients were classified as having normal cognition (PD-NC), mild cognitive impairment (PD-MCI), or PD dementia (PDD) based on Seoul Neuropsychological Screening Battery-II, which includes 31 subsets covering activities of daily living and 5 cognitive domains. They all had brain imaging with MRI and PET with 18F-N-(3-fluoropropyl)-2beta-carbon ethoxy-3beta-(4-iodophenyl) nortropane at baseline. Subsequently, standardized uptake value ratios (SUVRs) for regional dopamine availability and regional gray matter volumes were obtained using automated segmentation. These metrics were compared across cognitive status groups, and spatiotemporal progression patterns were analyzed using the Subtype and Stage Inference machine learning technique. Among 168 patients (mean age, 73.3 ± 6.1 years; 81 [48.2%] women), 65 had PD-NC, 65 had PD-MCI, and 38 had PDD. Patients with PD-MCI exhibited lower SUVRs (3.61 ± 1.31, p < 0.001) in the caudate than patients with PD-NC (4.43 ± 1.21) but higher SUVRs than patients with PDD (2.39 ± 1.06). Patients with PD-NC had higher thalamic SUVRs (1.55 ± 0.16, p < 0.001) than patients with both PD-MCI (1.45 ± 0.16) and PDD (1.38 ± 0.19). Regional deep gray matter volumes of the caudate (p = 0.015), putamen (p = 0.012), globus pallidus (p < 0.001), thalamus (p < 0.001), hippocampus (p < 0.001), and amygdala (p < 0.001) were more reduced in patients with PD-MCI or PDD than in patients with PD-NC, and the SUVR of the caudate correlated with caudate volume (r = 0.187, p = 0.015). Hippocampal atrophy was the initial change influencing cognitive impairment. The reduced dopamine availability of the thalamus preceded reductions in volume across most deep gray matter regions. Our finding underscores the association between decreased dopamine availability and volume of the caudate and thalamus with cognitive dysfunction in PD. The dopamine availability of the caudate and thalamus was reduced before the volume of the caudate and thalamus was decreased, highlighting the spatiotemporal association between dopaminergic and structural pathology in cognitive impairment in PD.

Controlling the pathological activity of parkinsonian basal nuclei with the basal ganglia network model under light stimulation in the three-state, four-state channelrhodopsin, and three-state halorhodopsin optogenetic models

Background. Parkinson’s disease (PD) is a neurological disorder caused by the dysfunction of the basal nuclei, especially the substantia nigra, and a decrease in dopamine levels in the neural circuits of this part. In this paper, to investigate the effects of optogenetic stimulation on parkinsonian nervous systems, a complete model of basal ganglia (BG, including subthalamic nucleus [STN], globus pallidus interna [GPi], globus pallidus externa [GPe], and thalamus [TH] neurons) was first selected to simulate the neurons of the basal nuclei and was developed for PD using three- and four-state optogenetic stimulation. Methods. For this purpose, channelrhodopsin-2 (ChETA), ChRwt, and halorhodopsin (NpHR) opsins were evaluated in three-state and four-state stimulation modes, and different stimulation conditions according to different parameters in the BG model were taken into consideration. Results. To verify the developed model, the obtained results were compared with the results of experimental studies. The amount of compliance for different stimulation conditions and various genes underwent investigation. The value of the error index was calculated to evaluate the performance of the BG model for each gene in three- and four-state stimulation conditions with different values of basic parameters, and the stimulation conditions that created the error index equal to zero were introduced as optimal conditions. Based on the results, the frequencies of 20 Hz and 200 Hz in the four-state ChRwt model and the frequency of 80 Hz in the three-state ChETA model have been suggested as optimal genes, frequencies, and models. Conclusion. The response of GPe neurons was consistent with the experimental results, and the response of other neurons was also similar to the response of GPe neurons. In optimal conditions, STN and GPe neurons could provide excitatory input and appropriate inhibitory input to GPi, respectively, and GPi neurons could provide appropriate inhibitory input to TH, and as a result, its function improved and the pathological effects of PD disappeared. Practical Implications. In this research, it has been attempted to improve the function of the basal nuclei of the brain by using optogenetic stimulation and the elimination of the pathological symptoms of PD.

Chronic Low-Grade Inflammation and Brain Structure in the Middle-Aged and Elderly Adults.

Low-grade inflammation (LGI) mainly acted as the mediator of the association of obesity and inflammatory diet with numerous chronic diseases, including neuropsychiatric diseases. However, the evidence about the effect of LGI on brain structure is limited but important, especially in the context of accelerating aging. This study was then designed to close the gap, and we leveraged a total of 37,699 participants from the UK Biobank and utilized inflammation score (INFLA-score) to measure LGI. We built the longitudinal relationships of INFLA-score with brain imaging phenotypes using multiple linear regression models. We further analyzed the interactive effects of specific covariates. The results showed high level inflammation reduced the volumes of the subcortex and cortex, especially the globus pallidus (β [95% confidence interval] = -0.062 [-0.083, -0.041]), thalamus (-0.053 [-0.073, -0.033]), insula (-0.052 [-0.072, -0.032]), superior temporal gyrus (-0.049 [-0.069, -0.028]), lateral orbitofrontal cortex (-0.047 [-0.068, -0.027]), and others. Most significant effects were observed among urban residents. Furthermore, males and individuals with physical frailty were susceptive to the associations. The study provided potential insights into pathological changes during disease progression and might aid in the development of preventive and control targets in an age-friendly city to promote great health and well-being for sustainable development goals.

Modulation of alpha oscillations by attention is predicted by hemispheric asymmetry of subcortical regions.

Evidence suggests that subcortical structures play a role in high-level cognitive functions such as the allocation of spatial attention. While there is abundant evidence in humans for posterior alpha band oscillations being modulated by spatial attention, little is known about how subcortical regions contribute to these oscillatory modulations, particularly under varying conditions of cognitive challenge. In this study, we combined MEG and structural MRI data to investigate the role of subcortical structures in controlling the allocation of attentional resources by employing a cued spatial attention paradigm with varying levels of perceptual load. We asked whether hemispheric lateralization of volumetric measures of the thalamus and basal ganglia predicted the hemispheric modulation of alpha-band power. Lateral asymmetry of the globus pallidus, caudate nucleus, and thalamus predicted attention-related modulations of posterior alpha oscillations. When the perceptual load was applied to the target and the distractor was salient caudate nucleus asymmetry predicted alpha-band modulations. Globus pallidus was predictive of alpha-band modulations when either the target had a high load, or the distractor was salient, but not both. Finally, the asymmetry of the thalamus predicted alpha band modulation when neither component of the task was perceptually demanding. In addition to delivering new insight into the subcortical circuity controlling alpha oscillations with spatial attention, our finding might also have clinical applications. We provide a framework that could be followed for detecting how structural changes in subcortical regions that are associated with neurological disorders can be reflected in the modulation of oscillatory brain activity.

Modulation of alpha oscillations by attention is predicted by hemispheric asymmetry of subcortical regions

Evidence suggests that subcortical structures play a role in high-level cognitive functions such as the allocation of spatial attention. While there is abundant evidence in humans for posterior alpha band oscillations being modulated by spatial attention, little is known about how subcortical regions contribute to these oscillatory modulations, particularly under varying conditions of cognitive challenge. In this study, we combined MEG and structural MRI data to investigate the role of subcortical structures in controlling the allocation of attentional resources by employing a cued spatial attention paradigm with varying levels of perceptual load. We asked whether hemispheric lateralization of volumetric measures of the thalamus and basal ganglia predicted the hemispheric modulation of alpha-band power. Lateral asymmetry of the globus pallidus, caudate nucleus, and thalamus predicted attention-related modulations of posterior alpha oscillations. When the perceptual load was applied to the target and the distractor was salient caudate nucleus asymmetry predicted alpha-band modulations. Globus pallidus was predictive of alpha-band modulations when either the target had a high load, or the distractor was salient, but not both. Finally, the asymmetry of the thalamus predicted alpha band modulation when neither component of the task was perceptually demanding. In addition to delivering new insight into the subcortical circuity controlling alpha oscillations with spatial attention, our finding might also have clinical applications. We provide a framework that could be followed for detecting how structural changes in subcortical regions that are associated with neurological disorders can be reflected in the modulation of oscillatory brain activity.

A novel splicing mutation DNAH5 c.13,338 + 5G > C is involved in the pathogenesis of primary ciliary dyskinesia in a family with primary familial brain calcification

BackgroundPrimary ciliary dyskinesia (PCD) is an autosomal recessive hereditary disease characterized by recurrent respiratory infections. In clinical manifestations, DNAH5 (NM_001361.3) is one of the recessive pathogenic genes. Primary familial brain calcification (PFBC) is a neurodegenerative disease characterized by bilateral calcification in the basal ganglia and other brain regions. PFBC can be inherited in an autosomal dominant or recessive manner. A family with PCD caused by a DNAH5 compound heterozygous variant and PFBC caused by a MYORG homozygous variant was analyzed.MethodsIn this study, we recruited three generations of Han families with primary ciliary dyskinesia combined with primary familial brain calcification. Their clinical phenotype data were collected, next-generation sequencing was performed to screen suspected pathogenic mutations in the proband and segregation analysis of families was carried out by Sanger sequencing. The mutant and wild-type plasmids were constructed and transfected into HEK293T cells instantaneously, and splicing patterns were detected by Minigene splicing assay. The structure and function of mutations were analyzed by bioinformatics analysis.ResultsThe clinical phenotypes of the proband (II10) and his sister (II8) were bronchiectasis, recurrent pulmonary infection, multiple symmetric calcifications of bilateral globus pallidus and cerebellar dentate nucleus, paranasal sinusitis in the whole group, and electron microscopy of bronchial mucosa showed that the ciliary axoneme was defective. There was also total visceral inversion in II10 but not in II8. A novel splice variant C.13,338 + 5G > C and a frameshift variant C.4314delT (p. Asn1438lysfs *10) were found in the DNAH5 gene in proband (II10) and II8. c.347_348dupCTGGCCTTCCGC homozygous insertion variation was found in the MYORG of the proband. The two pathogenic genes were co-segregated in the family. Minigene showed that DNAH5 c.13,338 + 5G > C has two abnormal splicing modes: One is that part of the intron bases where the mutation site located is translated, resulting in early translation termination of DNAH5; The other is the mutation resulting in the deletion of exon76.ConclusionsThe newly identified DNAH5 splicing mutation c.13,338 + 5G > C is involved in the pathogenesis of PCD in the family, and forms a compound heterozygote with the pathogenic variant DNAH5 c.4314delT lead to the pathogenesis of PCD.

Intraoperative DBS targeting of the globus pallidus internus by using motor evoked potentials

ObjectivesTarget localization for deep brain stimulation (DBS) is a crucial step that influences the clinical benefit of the DBS procedure together with the reduction of side effects. In this work, we address the feasibility of DBS target localization in the globus pallidus internus (GPi) aided by intraoperative motor evoked potentials (MEP) with emphasis on the reduction of capsular side effects. Material and methodsMicro-macroelectrode recordings were performed intraoperatively on 20 patients that underwent DBS treatment of the GPi (GPi-DBS). MEP were elicited intraoperatively by microelectrode stimulation during stereotactic DBS surgery. We studied the relationship between MEP thresholds and the internal capsule (IC) proximity. ResultsWe found a significant correlation between intraoperative MEP thresholds and IC proximity. ConclusionsWe provide further evidence of the role of MEPs for DBS target localization in the GPi, which extends and confirms the usefulness of MEPs as previously reported by DBS target localization studies dealing with the subthalamic and thalamic nuclei. Our approach is advantageous in that it provides criteria to determine the DBS target without the need to rely on a patient's response while avoiding capsular effects.

Volitional modulation of neuronal activity in the external globus pallidus by engagement of the cortical-basal ganglia circuit.

Volitional modulation of neural activity is not confined to the cortex but extends to various brain regions. Yet, it remains unclear whether neurons in the basal ganglia structure, the external globus pallidus (GPe), can be volitionally controlled. Here, we employed a volitional conditioning task to compare the volitional modulation of GPe and primary motor cortex (M1) neurons as well as the underlying circuits and control mechanisms. The results revealed that the volitional modulation of GPe neuronal activity engaged both M1 and substantia nigra pars reticulata (SNr) neurons, indicating the involvement of the cortex-GPe-SNr loop. In contrast, the volitional modulation of M1 neurons primarily occurred through the engagement of M1 local circuitry. Furthermore, lesioning M1 neurons did not affect the volitional learning or volitional control signal in GPe, whereas lesioning of GPe neurons impaired the learning process for the volitional modulation of M1 neuronal activity at the intermediate stage. Additionally, lesion of GPe neurons enhanced M1 neuronal activity when performing the volitional control task without reward delivery and a random reward test. Taken together, our findings demonstrated that GPe neurons could be volitionally controlled by engagement of the cortical-basal ganglia circuit and inhibit learning process for the volitional modulation of M1 neuronal activity by regulating M1 neuronal activity. Thus, GPe neurons can be effectively harnessed for independent volitional modulation for neurorehabilitation in patients with cortical damage. KEY POINTS: The cortical-basal ganglia circuit contributes to the volitional modulation of GPe neurons. Volitional modulation of M1 neuronal activity mainly engages M1 local circuitry. Bilateral GPe lesioning impedes volitional learning at the intermediate stages. Lesioning of GPe neurons inhibits volitional learning process by regulating M1 neuronal activity.

Frontal-striatal glucose metabolism and fatigue in patients with multiple sclerosis, long COVID, and COVID-19 recovered controls.

This study compared brain glucose metabolism using FDG-PET in the caudate nucleus, putamen, globus pallidus, thalamus, and dorsolateral prefrontal cortex (DLPFC) among patients with Long COVID, patients with fatigue, people with multiple sclerosis (PwMS) patients with fatigue, and COVID recovered controls. PwMS exhibited greater hypometabolism compared to long COVID patients with fatigue and the COVID recovered control group in all studied brain areas except the globus pallidus (effect size range 0.7-1.5). The results showed no significant differences in glucose metabolism between patients with Long COVID and the COVID recovered control group in these regions. These findings suggest that long COVID fatigue may involve non-CNS systems, neurotransmitter imbalances, or psychological factors not captured by FDG-PET, while MS-related fatigue is associated with more severe frontal-striatal circuit dysfunction due to demyelination and neurodegeneration. Symmetrical standardized uptake values (SUVs) between hemispheres in all groups imply that fatigue in these conditions may be related to global or network-level alterations rather than hemisphere-specific changes. Future studies should employ fine-grained analysis methods, explore other brain regions, and control for confounding factors to better understand the pathophysiology of fatigue in MS and long COVID. Longitudinal studies tracking brain glucose metabolism in patients with Long COVID could provide insights into the evolution of metabolic patterns as the condition progresses.

The Endoscopic Transorbital Approach for Vascular Surgery: An Anterior Circulation Anatomic Study, 2-Dimensional Operative Video.

Minimally invasive endoscopic approaches in cranial base surgery have been developing in the past decades. The transorbital (TO) route is one promising alternative, yet its adequacy for intracranial vascular lesions remains unclear. The present anatomic work aimed to test the feasibility and to provide a qualitative description of the endoscopic TO approach for the anterior circulation, namely the internal carotid artery and the middle cerebral artery. Seven embalmed adult cadaveric specimens (12 sides) were used in the study. Each side was approached in 3 successive steps: (1) Superior-eyelid TO approach, with great and lesser sphenoid wing removal. (2) Removal of anterior clinoid process (ACP). (3) Removal of the lateral orbital rim. All the procedures were performed under endoscopic view. The TO approach without removing the ACP allowed to dissect the sphenoidal and lateral segments of the Sylvian fissure with an adequate identification of the middle cerebral artery bifurcation in all specimens. The removal of the ACP allowed further dissection toward the opticocarotid cistern, with the identification of the ophthalmic, posterior communicating, and the anterior choroidal arteries. The internal carotid artery bifurcation and A1 segment were also readily identified. Finally, removal of the lateral orbital rim provided a wider and more comfortable access to the above-mentioned vascular structures. According to our anatomic data, the TO approach can be used to reach the main vascular components of the anterior circulation. This opens the field for exploring its application in the treatment of vascular pathology, particularly aneurysms.

Striatal projection neurons coexpressing dopamine D1 and D2 receptors modulate the motor function of D1- and D2-SPNs.

The role of the striatum in motor control is commonly assumed to be mediated by the two striatal efferent pathways characterized by striatal projection neurons (SPNs) expressing dopamine (DA) D1 receptors or D2 receptors (D1-SPNs and D2-SPNs, respectively), without regard to SPNs coexpressing both receptors (D1/D2-SPNs). Here we developed an approach to target these hybrid SPNs in mice and demonstrate that, although these SPNs are less abundant, they have a major role in guiding the motor function of the other two populations. D1/D2-SPNs project exclusively to the external globus pallidus and have specific electrophysiological features with distinctive integration of DA signals. Gain- and loss-of-function experiments indicate that D1/D2-SPNs potentiate the prokinetic and antikinetic functions of D1-SPNs and D2-SPNs, respectively, and restrain the integrated motor response to psychostimulants. Overall, our findings demonstrate the essential role of this population of D1/D2-coexpressing neurons in orchestrating the fine-tuning of DA regulation in thalamo-cortico-striatal loops.

Deep Brain Stimulation of the Subthalamic Nucleus vs. Globus Pallidus Internus in the Treatment of Parkinson’s Disease: A Systematic Review

Abstract Background Parkinson’s disease (PD) is a very common debilitating disease especially in the elderly population. Bilateral stimulation of the subthalamic nucleus or the globus pallidus internus provides significant motor benefits for patients with advanced Parkinson’s disease, while reducing dyskinesia and motor fluctuation. High frequency stimulation of the STN and the GPi is relatively safe. The effects are stable even after 1 year of stimulation. Aim of the Work The primary goal of the current review is to compare the efficacy of using the Subthalamic Nucleus (STN) vs. the Globus Pallidus Internus (GPi) as the primary target for Deep Brain Stimulation (DBS) in the treatment of Parkinson disease (PD); in terms of improved motor function measured using the Unified Parkinson's Disease Rating Scale (UPDRS), psychiatric symptoms, rate of reduction of medication, and complications. This will be done through a systematic review of literature addressing this research question. Patients and Methods In this Review, the authors are aiming at the analysis of the collective outcomes from studies comparing bilateral deep brain stimulation of the Subthalamic Nucleus and the Globus Pallidus Internus in the management of idiopathic Parkinson’s disease. The following electronic databases were searched for included articles: PubMed, Google Scholar, EMBASE, Science Direct, Cochrane database of systematic reviews, using the keywords “Parkinson’s disease – treatment – management – deep brain stimulation – subthalamic – globus pallidus internus” in different combinations. Also, manual search were conducted for reference lists of included articles. Limiting the search in English. The information sources previously mentioned were searched from 2000 to 2021. Results A total of 594 patients underwent STN-DBS, with a mean change in total UPDRSIII score of 3.26 on medication and 25.04 off medication. A total of 446 patients underwent GPi-DBS, with a mean change in total UPDRSIII score of 4.75 on medication and 19.31 off medication. There was a higher change for GPi on medication that was statistically significant with a p value (˂0.001), while off medication STN caused a higher change that was also statistically significant with a p value (˂0.001). We observed a statistically significant higher average improvement in ADLs after STN-DBS than GPi, however, non- motor function improvements were greater after GPi DBS than STN DBS. Conclusion Based on our systematic review and other available data in the literature, the STN may be the preferred target for DBS in consideration of motor function improvement, medication reduction, and economic efficiency, although GPI stimulation has some advantages in terms of mood and cognition. Treatment decisions should be individualized and based on patients’ specific symptoms and expectations. Additional well-designed multicenter clinical trials that can minimize bias are needed, especially for evaluation of the long-term outcomes of the two stimulation targets.

Probabilistic Tractography-Based Tremor Network Connectivity in Tremor Dominant Parkinson's Disease and Essential Tremor plus.

Background: The basal ganglia-thalamocortical (BGTC) and cerebello-thalamocortical (CTC) networks are implicated in tremor genesis; however, exact contributions across disorders have not been studied. Objective: Evaluate the structural connectivity of BGTC and CTC in tremor-dominant Parkinson's disease (TDPD) and essential tremor plus (ETP) with the aid of probabilistic tractography and graph theory analysis. Methods: Structural connectomes of the BGTC and CTC were generated by probabilistic tractography for TDPD (n = 25), ETP (ET with rest tremor, n = 25), and healthy control (HC, n = 22). The Brain Connectivity Toolbox was used for computing standard topological graph measures of segregation, integration, and centrality. Tremor severity was ascertained using the Fahn-Tolosa-Marin tremor rating scale (FTMRS). Results: There was no difference in total FTMRS scores. Compared with HC, TDPD had a lower global efficiency and characteristic path length. Abnormality in segregation, integration, and centrality of bilateral putamen, globus pallidus externa (GPe), and GP interna (GPi), with reduction of centrality of right caudate and cerebellar lobule 8, was observed. ETP showed reduction in segregation and integration of right GPe and GPi, ventrolateral posterior nucleus, and centrality of right putamen, compared with HC. Differences between TDPD and ETP were a reduction of strength of the right putamen, and lower clustering coefficient, local efficiency, and strength of the left GPi in TDPD. Conclusions: Contrary to expectations, TDPD and ETP may not be significantly different with regard to tremor pathogenesis, with definite overlaps. There may be fundamental similarities in network disruption across different tremor disorders with the same tremor activation patterns, along with disease-specific changes.

Precision targeting in the globus pallidus interna: insights from the multicenter, prospective, blinded VA/NINDS CSP 468 study.

Deep brain stimulation (DBS) targeting the globus pallidus interna (GPi) has been shown to significantly improve motor symptoms for the treatment of medication-refractory Parkinson's disease. Yet, heterogeneity in clinical outcomes persists, possibly due to suboptimal target identification within the GPi. By leveraging robust sampling of the GPi and 6-month postsurgical outcomes, this study aims to determine optimal symptom-specific GPi DBS targets. In this study, the authors analyzed the anatomical lead location and 6-month postsurgical, double-blinded outcome measures of 86 patients who underwent bilateral GPi DBS. These patients were selected from the multicenter Veterans Affairs (VA)/National Institutes of Neurological Disorders and Stroke (NINDS) Cooperative Studies Program (CSP) 468 study to identify the optimal target zones ("sweet spots") for the control of overall motor (United Parkinson's Disease Rating Scale [UPDRS]-III), axial, tremor, rigidity, and bradykinesia symptoms. Lead coordinates were normalized to Montreal Neurological Institute space and the optimal target zones were identified and validated using a leave-one-patient-out approach. The authors' findings revealed statistically significant optimal target zones for UPDRS-III (R = 0.37, p < 0.001), axial (R = 0.22, p = 0.042), rigidity (R = 0.20, p = 0.021), and bradykinesia (R = 0.23, p = 0.004) symptoms. These zones were localized within the primary motor and premotor subdivisions of the GPi. Interestingly, these zones extended beyond the GPi lateral border into the GPi-globus pallidus externa (GPe) lamina and into the GPe, but they did not reach the GPi ventral border, challenging traditional surgical approaches based on pallidotomies. Drawing upon a robust dataset, this research effectively delineates specific optimal target zones for not only overall motor improvement but also symptom subscores. These insights hold the potential to enhance the precision of targeting in subsequent bilateral GPi DBS surgical procedures.