Basal Ganglia Research Articles

Location matters: altered interhemispheric homotopic connectivity in post-stroke dyskinesia.

Motor impairment is the most prevalent consequence following a stroke. Interhemispheric homotopic connectivity, which varies regionally and hierarchically along the axis of the somatomotor-association cortex, plays a critical role in sustaining normal motor functions. However, the impact of strokes occurring in various locations on homotopic connectivity is not fully understood. This study aimed to explore how motor deficits resulting from acute strokes in different locations influence homotopic connectivity. Eighty-four acute ischemic stroke patients with dyskinesia were recruited and divided into four demographically-matched subgroups based on stroke locations: Group 1 (G1; frontoparietal, n = 15), Group 2 (G2; radiation coronal, n = 16), Group 3 (G3; basal ganglia, n = 30), and Group 4 (G4; brain stem, n = 23). An additional 37 demographically-matched healthy controls were also recruited in the study. Multimodal MRI data, motor function assessments, and cognitive tests were gathered for analysis. Interhemispheric homotopic functional and structural connectivity were measured using resting-state functional MRI and diffusion tensor imaging, respectively. These measurements were then correlated with motor function scores to investigate the relationships. Voxel-mirrored homotopic connectivity (VMHC) analysis showed that strokes in the frontoparietal and basal ganglia regions led to diminished homotopic connectivity in the somatosensory/motor cortex. In contrast, strokes in the radiation coronal and brainstem regions affected subcortical motor circuits. Structural homotopic connectivity analysis using diffusion tensor imaging showed that frontoparietal and basal ganglia strokes predominantly affected association fibers, while radiation coronal and brainstem strokes caused widespread disruption in the integrity of both cortical-cortical and cortical-subcortical white matter fibers. Correlation analyses demonstrated significant associations between the Fugl-Meyer Assessment (FMA), Modified Barthel Index (MBI), and National Institutes of Health Stroke Scale (NIHSS) scores with the VMHC in the inferior temporal gyrus for G1 (G1; r = 0.838, p < 0.001; r = 0.793, p < 0.001; and r = -0.834, p < 0.001, respectively). No statistically significant associations were observed in Groups 2, 3, and 4. Our results suggest that motor deficits following strokes in various regions involve distinct pathways from cortical to subcortical areas. Alterations in lesion topography and regional functional homotopy provide new insights into the understanding of neural underpinnings of post-stroke dyskinesia.

Associated with hyperglycemia: a rare cause of hyperkinetic movement disorders

Diabetic striopathy, a neurological disorder associated with diabetes mellitus, is characterized by specific changes in basal ganglia structures, particularly the striatum. Although its precise etiology remains elusive, chronic hyperglycemia, microvascular dysfunction, oxidative stress, and inflammation are implicated. Diagnosis relies on clinical assessment and neuroimaging, revealing characteristic basal ganglia abnormalities. Management focuses on optimizing glycemic control and alleviating symptoms. We present an 83-year-old woman with abrupt-onset unilateral chorea-ballismus as a case illustration, showcasing diagnostic and therapeutic approaches. Understanding the underlying mechanisms and refining management strategies are crucial for effectively addressing this complex neurological complication of diabetes mellitus.

INTERRELATION BETWEENCARDIAC CONDUCTION ANOMALIES AND RADIOLOGICALFEATURES OF FAHRS SYNDROME: AFACT OR COINCIDENCE? CASE REPORT AND REVIEW OF THE LITTERATURE

Introduction:Fahrs syndrome is a rare, slowly progressive, neurodegenerativedisorder, characterized by extensive, bilateral, and symmetrical basal ganglia calcification. It isassociatedwithneuropsychiatric manifestations and gradually progressive cognitive impairment. Fahrs syndrome is the secondaryform of brain calcification thatiscaused by variousmetabolic, infectious, or degenerativediseases. Case report:An old manwasadmittedto ourdepartmentwithrecurrentepisodes of syncope. An electrocardiogramrevealedcomplete AV block.Laboratoryresultsdisclosedhypocalcemia, pseudo hypoparathyroidism, and hyperphosphatemia. Computedtomographyrevealedintracranial calcifications suggestiveofFahrs syndrome. Conclusion:Fahrs syndrome is a rare anatomo-clinical and radiologicalentity, with multiple clinical and etiological aspects. The pathophysiologicalmechanism of the lesionsremainspoorlyunderstood, even more cardiacfeaturesthatmaycause, but is set to benefitfromadvances in functionalneuroimaging.

Neuropsychiatric Manifestations and Neuroimaging Changes of Neurologic Wilson Disease–A Cross Sectional Study

Background: Wilson disease is genetic disorder of copper metabolism which causes hepatic &amp; neurologic manifestation mainly. Chelator therapy is usually given as first line treatment in symptomatic wilson disease. Objective: Objective of our study was to evaluate the neuropsychiatric menufestations of wilson disease. Methods: A Cross sectional study was conducted at Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, a tertiary care premier Postgraduate Medical Institution of Bangladesh. Forty five (45) patients of neurologic wilson disease were evaluated at In-patient department of Paediatric Neurology, during the period of January 2015 to December 2020. Diagnosis of Neurologic wilson disease was done, based on the characteristic clinical features of progressive deterioration of scholastic performances, dysarthria and gait disorder along with ophthalmologic findings, biochemical &amp; neuroimaging findings. Results: Total numbers of studied cases were 45. Mean age was 124.65± 20.69 months and male to female ratio was 1.8:1. Most of the patient (83.33%) arrived from poor socio-economic background and rural area (66.67%) of Bangladesh. Among them 20.0% had history of consanguineous mating parents and 17.78% had another affected sibs. Common presenting features were progressive deterioration of school performance (89.74%), gait disturbance (92.31%), dysarthria (92.31%) and dystonia (41.03%) of our studied children. Neuropsychiatric manifestations were very common among the affected children. Changes in behavior was present in 62.22% cases, and among them mania were present in 57.77% children. Other common neuropsychiatric manifestations were depression (35.55%), generalized anxiety disorder in 31.11% and loss of memory in 20% cases. Ophthalmological manifestations like KF ring (83.33%) also found in majority of patient. Neuroimaging study showed basal ganglia hyperintensity in 63.63.% , white matter hyper intense signal changes 18.18% cases and ischemic change in grey matter in 18.18% cases. Conclusion: In our study about two third cases of Neurologic Wilson diseases may present with Neuropsychiatric manifestations in children. Behavior changes were commonest neuropsychiatric manifestations which includes depression, mania, generalized anxiety disorder and loss of memory.In neuroimaging study bilateral basal ganglia hyperintensity were found in about three-fourth cases of our studied children. J Bangladesh Coll Phys Surg 2024; 42: 144-148

Pantothenate kinase-associated neurodegeneration (PKAN) a rare neurodegenerative disease-Two case reports

Neurodegeneration with brain iron accumulation (NBIA) is a subtype of inherited metabolic disorders. It includes pantothenate kinase-associated neurodegeneration (PKAN), which is a rare autosomal recessive disorder caused by the mutation of pantothenate kinase 2-gene (PANK2). It affects the deep grey matter nuclei causing progressive extra pyramidal motor impairment. We present two cases who are presented in our department with walking difficulty, dystonia and dysarthria. MRI of brain (T2) showed- hyper intensity of the basal ganglia with the classic eye-of-the-tiger sign and one child's genetic study revealed mutation in PANK2 gene. We managed them with anti dystonic drugs along with iron chelating agent. J Bangladesh Coll Phys Surg 2024; 42: 209-213

A rare case of recurrent biballism

Diabetic striatopathy (DS) is a relatively new entity with growing literature expanding our knowledge of the same. It is commonly seen in elderly Asian females with long-term uncontrolled type 2 diabetes mellitus presenting with hemichorea or hemiballism with characteristic reversible imaging findings involving various basal ganglia structures. While various different types of presentations with variable responses to therapy in terms of treatment modality and recovery time have been reported, there is very little data on the recurrence of this entity. We, hereby, present an interesting case of DS, which had a rare presentation in the form of biballism. Our patient had an initial swift recovery with glycemic control alone and thereafter a ropinirole-induced recurrence in spite of good glycemic control, which was rather difficult to control. This case emphasizes the need for clinicians to be aware of the various presentations of DS and to be cautious in the use of drugs with the potential to cause movement disorders in such a patient.

Identifying ADHD-Related Abnormal Functional Connectivity with a Graph Convolutional Neural Network.

Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder that is characterized by inattention, hyperactivity, and impulsivity. The neural mechanisms underlying ADHD remain inadequately understood, and current approaches do not well link neural networks and attention networks within brain networks. Our objective is to investigate the neural mechanisms related to attention and explore neuroimaging biological tags that can be generalized within the attention networks. In this paper, we utilized resting-state functional magnetic resonance imaging data to examine the differential functional connectivity network between ADHD and typically developing individuals. We employed a graph convolutional neural network model to identify individuals with ADHD. After classification, we visualized brain regions with significant contributions to the classification results. Our results suggest that the frontal, temporal, parietal, and cerebellar regions are likely the primary areas of dysfunction in individuals with ADHD. We also explored the relationship between regions of interest and attention networks, as well as the connection between crucial nodes and the distribution of positively and negatively correlated connections. This analysis allowed us to pinpoint the most discriminative brain regions, including the right orbitofrontal gyrus, the left rectus gyrus and bilateral insula, the right inferior temporal gyrus and bilateral transverse temporal gyrus in the temporal region, and the lingual gyrus of the occipital lobe, multiple regions of the basal ganglia and the upper cerebellum. These regions are primarily involved in the attention executive control network and the attention orientation network. Dysfunction in the functional connectivity of these regions may contribute to the underlying causes of ADHD.

Protocol for combined N-of-1 trials to assess cerebellar neurostimulation for movement disorders in children and young adults with dyskinetic cerebral palsy.

Movement and tone disorders in children and young adults with cerebral palsy are a great source of disability. Deep brain stimulation (DBS) of basal ganglia targets has a major role in the treatment of isolated dystonias, but its efficacy in dyskinetic cerebral palsy (DCP) is lower, due to structural basal ganglia and thalamic damage and lack of improvement of comorbid choreoathetosis and spasticity. The cerebellum is an attractive target for DBS in DCP since it is frequently spared from hypoxic ischemic damage, it has a significant role in dystonia network models, and small studies have shown promise of dentate stimulation in improving CP-related movement and tone disorders. Ten children and young adults with DCP and disabling movement disorders with or without spasticity will undergo bilateral DBS in the dorsal dentate nucleus, with the most distal contact ending in the superior cerebellar peduncle. We will implant Medtronic Percept, a bidirectional neurostimulator that can sense and store brain activity and deliver DBS therapy. The efficacy of cerebellar DBS in improving quality of life and motor outcomes will be tested by a series of N-of-1 clinical trials. Each N-of-1 trial will consist of three blocks, each consisting of one month of effective stimulation and one month of sham stimulation in a random order with weekly motor and quality of life scales as primary and secondary outcomes. In addition, we will characterize abnormal patterns of cerebellar oscillatory activity measured by local field potentials from the intracranial electrodes related to clinical assessments and wearable monitors. Pre- and 12-month postoperative volumetric structural and functional MRI and diffusion tensor imaging will be used to identify candidate imaging markers of baseline disease severity and response to DBS. Our goal is to test a cerebellar neuromodulation therapy that produces meaningful changes in function and well-being for people with CP, obtain a mechanistic understanding of the underlying brain network disorder, and identify physiological and imaging-based predictors of outcomes useful in planning further studies. ClinicalTrials.gov NCT06122675, first registered November 7, 2023.

Selective disrupted gray matter volume covariance of amygdala subregions in schizophrenia.

Although extensive structural and functional abnormalities have been reported in schizophrenia, the gray matter volume (GMV) covariance of the amygdala remain unknown. The amygdala contains several subregions with different connection patterns and functions, but it is unclear whether the GMV covariance of these subregions are selectively affected in schizophrenia. To address this issue, we compared the GMV covariance of each amygdala subregion between 807 schizophrenia patients and 845 healthy controls from 11 centers. The amygdala was segmented into nine subregions using FreeSurfer (v7.1.1), including the lateral (La), basal (Ba), accessory-basal (AB), anterior-amygdaloid-area (AAA), central (Ce), medial (Me), cortical (Co), corticoamygdaloid-transition (CAT), and paralaminar (PL) nucleus. We developed an operational combat harmonization model for 11 centers, subsequently employing a voxel-wise general linear model to investigate the differences in GMV covariance between schizophrenia patients and healthy controls across these subregions and the entire brain, while adjusting for age, sex and TIV. Our findings revealed that five amygdala subregions of schizophrenia patients, including bilateral AAA, CAT, and right Ba, demonstrated significantly increased GMV covariance with the hippocampus, striatum, orbitofrontal cortex, and so on (permutation test, P< 0.05, corrected). These findings could be replicated in most centers. Rigorous correlation analysis failed to identify relationships between the altered GMV covariance with positive and negative symptom scale, duration of illness, and antipsychotic medication measure. Our research is the first to discover selectively impaired GMV covariance patterns of amygdala subregion in a large multicenter sample size of patients with schizophrenia.

Machine learning models for diagnosis of essential tremor and dystonic tremor using grey matter morphological networks

BackgroundEssential tremor (ET) and dystonic tremor (DT) are the two most common tremor disorders, and misdiagnoses are very common due to similar tremor symptoms. In this study, we explore the structural network mechanisms of ET and DT using brain grey matter (GM) morphological networks and combine those with machine learning models. Methods3D-T1 structural images of 75 ET patients, 71 DT patients, and 79 healthy controls (HCs) were acquired. We used voxel-based morphometry to obtain GM images and constructed GM morphological networks based on the Kullback-Leibler divergence-based similarity (KLS) method. We used the GM volumes, morphological relations, and global topological properties of GM-KLS morphological networks as input features. We employed three classifiers to perform the classification tasks. Moreover, we conducted correlation analysis between discriminative features and clinical characteristics. Results16 morphological relations features and 1 global topological metric were identified as the discriminative features, and mainly involved the cerebello-thalamo-cortical circuits and the basal ganglia area. The Random Forest (RF) classifier achieved the best classification performance in the three-classification task, achieving a mean accuracy (mACC) of 78.7%, and was subsequently used for binary classification tasks. Specifically, the RF classifier demonstrated strong classification performance in distinguishing ET vs. HCs, ET vs. DT, and DT vs. HCs, with mACCs of 83.0 %, 95.2 %, and 89.3 %, respectively. Correlation analysis demonstrated that four discriminative features were significantly associated with the clinical characteristics. ConclusionThis study offers new insights into the structural network mechanisms of ET and DT. It demonstrates the effectiveness of combining GM-KLS morphological networks with machine learning models in distinguishing between ET, DT, and HCs.

Gray–white matter contrast reversal on T1-weighted spin-echo in postmortem brain

PurposeThe image contrast of postmortem magnetic resonance imaging (MRI) may differ from that of antemortem MRI because of circulator arrest, changes in postmortem tissue, and low-body-temperature scanning conditions. In fact, we have found that the signal intensity of white matter (WM) on T1-weighted spin-echo (T1WSE) images of the postmortem brain was lower than that of gray matter (GM), which resulted in image contrast reversal between GM and WM relative to the living brain. However, the reason for this phenomenon is unclear. Therefore, the aim of this study is to clarify the reason why image contrast reversal occurs between GM and WM of the postmortem brain. Materials and methodsTwenty-three corpses were included in the study (mean age, 60.6 years; range: 19–60 years; mean rectal temperature at scan, 6.9℃; range: 4–11℃). On a 1.5 T MRI system, postmortem T1W-SE MRI of the brain was conducted in the 23 corpses prior to medico-legal autopsy. Next, T1 and T2 of the GM and WM at the level of the basal ganglia were determined in the same participants using inversion recovery and multiple SE sequences, respectively. The proton density (PD) was also calculated from the T1 and T2 images (in the same slice). ResultsT1W-SE image contrast between the GM and WM of all postmortem brains was inverted relative to the living brain. T1 (579 ms in GM and 307 ms in WM) and PD (64 in GM and 44 in WM) of the postmortem brain decreased compared with the living brain. While T1 of WM/GM remained below 1 even postmortem, the PD of WM/GM decreased. T2 (110 ms in GM and 98 ms in WM) of the postmortem brain did not differ from the living brain. ConclusionThe decrease in PD of WM/GM in the postmortem brain may be the major driver of contrast reversal between the GM and WM relative to the living brain.

A case of nonketotic hyperglycemia without movement anomalies: MRI findings

In our case report, we aimed to describe a patient with nonketotic hyperglycemia who was admitted to the emergency department with left basal ganglion involvement presenting with a stroke-like picture without movement anomalies.

Differential Synaptic Loss in β-Amyloid Positive Versus β-Amyloid Negative Corticobasal Syndrome.

The corticobasal syndrome (CBS) is a complex asymmetric movement disorder, with cognitive impairment. Although commonly associated with the primary 4-repeat-tauopathy of corticobasal degeneration, clinicopathological correlation is poor, and a significant proportion is due to Alzheimer's disease (AD). Synaptic loss is a pathological feature of many clinical and preclinical tauopathies. We therefore measured the degree of synaptic loss in patients with CBS and tested whether synaptic loss differed according to β-amyloid status. Twenty-five people with CBS, and 32 age-/sex-/education-matched healthy controls participated. Regional synaptic density was estimated by [11C]UCB-J non-displaceable binding potential (BPND), AD-tau pathology by [18F]AV-1451 BPND, and gray matter volume by T1-weighted magnetic resonance imaging. Participants with CBS had β-amyloid imaging with 11C-labeled Pittsburgh Compound-B ([11C]PiB) positron emission tomography. Symptom severity was assessed with the progressive supranuclear palsy-rating-scale, the cortical basal ganglia functional scale, and the revised Addenbrooke's Cognitive Examination. Regional differences in BPND and gray matter volume between groups were assessed by ANOVA. Compared to controls, patients with CBS had higher [18F]AV-1451 uptake, gray matter volume loss, and reduced synaptic density. Synaptic loss was more severe and widespread in the β-amyloid negative group. Asymmetry of synaptic loss was in line with the clinically most affected side. Distinct patterns of [11C]UCB-J and [18F]AV-1451 binding and gray matter volume loss, indicate differences in the pathogenic mechanisms of CBS according to whether it is associated with the presence of Alzheimer's disease or not. This highlights the potential for different therapeutic strategies in CBSs. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Atypical procedural learning in children with developmental coordination disorder: A combined behavioral and neuroimaging study

While procedural learning (PL) has been implicated in delayed motor skill observed in developmental coordination disorder (DCD), few studies have considered the impact of co-occurring attentional problems. Furthermore, the neurostructural basis of PL in children remains unclear. We investigated PL in children with DCD while controlling for inattention symptoms, and examined the role of fronto-basal ganglia-cerebellar morphology in PL. Fifty-nine children (6–14 years; nDCD = 19, ncontrol = 40) completed the serial reaction time (SRT) task to measure PL. The Attention-Deficit Hyperactivity Disorder Rating Scale-IV was administered to measure inattention symptoms. Structural T1 images were acquired for a subset of participants (nDCD = 10, ncontrol = 28), and processed using FreeSurfer. Volume was extracted for the cerebellum, basal ganglia, and frontal regions. After controlling for inattention symptoms, the reaction time profile of controls was consistent with learning on the SRT task. This was not the case for those with DCD. SRT task performance was positively correlated with cerebellar cortical volume, and children with DCD trended towards lower cerebellar volume compared to controls. Children with DCD may not engage in PL during the SRT task in the same manner as controls, with this differential performance being associated with atypical cerebellar morphology.

Investigating underlying brain structures and influence of mild and subjective cognitive impairment on dual-task performance in people with Parkinson’s disease

Cognitive impairment can affect dual-task abilities in Parkinson’s disease (PD), but it remains unclear whether this is also driven by gray matter alterations across different cognitive classifications. Therefore, we investigated associations between dual-task performance during gait and functional mobility and gray matter alterations and explored whether these associations differed according to the degree of cognitive impairment. Participants with PD were classified according to their cognitive function with 22 as mild cognitive impairment (PD-MCI), 14 as subjective cognitive impairment (PD-SCI), and 20 as normal cognition (PD-NC). Multiple regression models associated dual-task absolute and interference values of gait speed, step-time variability, and reaction time, as well as dual-task absolute and difference values for Timed Up and Go (TUG) with PD cognitive classification. We repeated these regressions including the nucleus basalis of Meynert, dorsolateral prefrontal cortex, and hippocampus. We additionally explored whole-brain regressions with dual-task measures to identify dual-task-related regions. There was a trend that cerebellar alterations were associated with worse TUG dual-task in PD-SCI, but also with higher dual-task gait speed and higher dual-task step-time variability in PD-NC. After multiple comparison corrections, no effects of interest were significant. In summary, no clear set of variables associated with dual-task performance was found that distinguished between PD cognitive classifications in our cohort. Promising but non-significant trends, in particular regarding the TUG dual-task, do however warrant further investigation in future large-scale studies.

Diffusion Mri in Intracranial Hypertension: Quantitative Assesment.

Intracranial hypertension (IH) is a neurological disease that is characterized by increased intracranial pressure. Idiopathic intracranial hypertension (IIH) is characterized by an increase in intracranial pressure without an underlying neuroradiological cause (1-3). The IH that is associated with a reason such as a mass, hydrocephalus, or drug use, is referred to as secondary intracranial hypertension (SIH). We aimed to detect determine whether the increased intracranial pressure causes a change in the diffusion values of brain in the diffusion MRI images. The study includes 24 consecutive patients that were diagnosed with IIH and 18 consecutive patients that were diagnosed with secondary intracranial hypertension (SIH). The control group included 24 patients. Measurement of apparent diffusion coefficient (ADC) was performed using DWI sections obtained from subcortical white matter and the cortex of the frontal lobe in the basal ganglia plane, caudate nucleus head, thalamus, the posterior leg of the internal capsule, corpus callosum splenium; in the centrum semiovale plane, from the central white matter region. with 1.5T MRI using b=500s/mm2 and b=1000s/mm2 values both in patients and control groups. Mean ADC values were compared between IIH, SIH patients and control groups. The ADC values from the head of the caudate nucleus and the cortex were significantly higher in the IIH group, compared to the control group. When the ADC values of the SIH and control groups were compared, it was found that some of the ADC measurements (subcortical white matter, cortex and semioval center) were significantly different. The comparison of the IIH and the SIH groups revealed that the ADC measurements central white matter in the centrum semiovale, the subcortical white matter and the posterior leg of the internal capsule were significantly different. Conclusıons: We have found increased diffusion IIH and SIH patients, which supports the development of brain edema. Even though the mechanism of the brain edema in IIH are not entirely clear, it is thought that the mechanism is different from the brain edema caused by a mass or a sinus thrombosis.

Structural Brain Connectivity and Treatment Improvement in Mood Disorder.

Background: The treatment of depressive episodes is well established, with clearly demonstrated effectiveness of antidepressants and psychotherapies. However, more than one-third of depressed patients do not respond to treatment. Identifying the brain structural basis of treatment-resistant depression could prevent useless pharmacological prescriptions, adverse events, and lost therapeutic opportunities. Methods: Using diffusion magnetic resonance imaging, we performed structural connectivity analyses on a cohort of 154 patients with mood disorder (MD) and 77 sex- and age-matched healthy control (HC) participants. To assess illness improvement, the patients with MD went through two clinical interviews at baseline and at 6-month follow-up and were classified based on the Clinical Global Impression-Improvement score into improved or not-improved (NI). First, the threshold-free network-based statistics (NBS) was conducted to measure the differences in regional network architecture. Second, nonparametric permutations tests were performed on topological metrics based on graph theory to examine differences in connectome organization. Results: The threshold-free NBS revealed impaired connections involving regions of the basal ganglia in patients with MD compared with HC. Significant increase of local efficiency and clustering coefficient was found in the lingual gyrus, insula, and amygdala in the MD group. Compared with the NI, the improved displayed significantly reduced network integration and segregation, predominately in the default-mode regions, including the precuneus, middle temporal lobe, and rostral anterior cingulate. Conclusions: This study highlights the involvement of regions belonging to the basal ganglia, the fronto-limbic network, and the default mode network, leading to a better understanding of MD disease and its unfavorable outcome.

Rethinking the external globus pallidus and information flow in cortico-basal ganglia-thalamic circuits.

For decades, the external globus pallidus (GPe) has been viewed as a passive way-station in the indirect pathway of the cortico-basal ganglia-thalamic (CBGT) circuit, sandwiched between striatal inputs and basal ganglia outputs. According to this model, one-way descending striatal signals in the indirect pathway amplify the suppression of downstream thalamic nuclei by inhibiting GPe activity. Here, we revisit this assumption, in light of new and emerging work on the cellular complexity, connectivity and functional role of the GPe in behaviour. We show how, according to this new circuit-level logic, the GPe is ideally positioned for relaying ascending and descending control signals within the basal ganglia. Focusing on the problem of inhibitory control, we illustrate how this bidirectional flow of information allows for the integration of reactive and proactive control mechanisms during action selection. Taken together, this new evidence points to the GPe as being a central hub in the CBGT circuit, participating in bidirectional information flow and linking multifaceted control signals to regulate behaviour.

Long-range projections of oxytocin neurons in the marmoset brain.

The neurohormone oxytocin (OT) has become a major target for the development of novel therapeutic strategies to treat psychiatric disorders such as autism spectrum disorder because of its integral role in governing many facets of mammalian social behavior. Whereas extensive work in rodents has produced much of our knowledge of OT, we lack basic information about its neurobiology in primates making it difficult to interpret the limited effects that OT manipulations have had in human patients. In fact, previous studies have revealed only limited OT fibers in primate brains. Here, we investigated the OT connectome in marmoset using immunohistochemistry, and mapped OT fibers throughout the brains of adult male and female marmoset monkeys. We found extensive OT projections reaching limbic and cortical areas that are involved in the regulation of social behaviors, such as the amygdala, the medial prefrontal cortex, and the basal ganglia. The pattern of OT fibers observed in marmosets is notably similar to the OT connectomes described in rodents. Our findings here contrast with previous results by demonstrating a broad distribution of OT throughout the marmoset brain. Given the prevalence of this neurohormone in the primate brain, methods developed in rodents to manipulate endogenous OT are likely to be applicable in marmosets.

Loss of Midbrain Dopamine Neurons Does Not Alter GABAergic Inhibition Mediated by Parvalbumin-Expressing Interneurons in Mouse Primary Motor Cortex.

The primary motor cortex (M1) integrates sensory and cognitive inputs to generate voluntary movement. Its functional impairments have been implicated in the pathophysiology of motor symptoms in Parkinson's disease (PD). Specifically, dopaminergic degeneration and basal ganglia dysfunction entrain M1 neurons into the abnormally synchronized bursting pattern of activity throughout the cortico-basal ganglia-thalamocortical network. However, how degeneration of the midbrain dopaminergic neurons affects the anatomy, microcircuit connectivity, and function of the M1 network remains poorly understood. The present study examined whether and how the loss of dopamine (DA) affects the morphology, cellular excitability, and synaptic physiology of Layer 5 parvalbumin-expressing (PV+) cells in the M1 of mice of both sexes. Here, we reported that loss of midbrain dopaminergic neurons does not alter the number, morphology, and physiology of Layer 5 PV+ cells in M1. Moreover, we demonstrated that the number of perisomatic PV+ puncta of M1 pyramidal neurons as well as their functional innervation of cortical pyramidal neurons were not altered following the loss of DA. Together, the present study documents an intact GABAergic inhibitory network formed by PV+ cells following the loss of midbrain dopaminergic neurons.