Investigation of Posture/Balance Disorder and Pd-related Pain by Using Diffusion Tensor Imaging and Transcranial Doppler

Background: Posture/balance disorder and pain are both present in Parkinson's patients, but their neural basis remain unclear. To investigate the central mechanism of posture/balance disorder and PD-related pain in Parkinson's disease by using diffusion tensor imaging (DTI) and tract-based spatial statistics (TBSS), combined with Transcranial Doppler (TCD). Results: It was found that the dose of levodopa, UPDRSⅡ and UPDRSⅢ were higher value in the group with higher score of posture/balance. In the more severe posture/balance disorder group, the fiber bundles of the prefrontal cortex, anterior cingulate cortex and basal ganglia were more likely to be affected. In addition, the DTI parameter values of the three brain regions had a significant correlation with the parameter values of the corresponding arteries. In the analysis of PD-related pain, the white matter fiber bundles from the midbrain to the basal ganglia increased in patients with PD-related pain. There were no statistic difference in prevalence of PD-related pain was found between different groups according to posture/balance. Conclusions: Posture and balance in PD were correlated with the severity of the disease and the dosage of compound levodopa. Posture and balance in PD were related to changes in the white matter integrity of the prefrontal cortex, anterior cingulate cortex and basal ganglia. The function of cerebral arteries had contributions to white matter integrity of these area and posture/balance. PD-related pain was positively correlated with sleep score. Patients with PD-related pain had an increase in the fiber projection from the midbrain to the basal ganglia. No relation was found between posture/balance disorder with PD-related pain.

Neuroinflammatory Profiling in SIV-Infected Chinese-Origin Rhesus Macaques on Antiretroviral Therapy

The central nervous system (CNS) HIV reservoir is an obstacle to achieving an HIV cure. The basal ganglia harbor a higher frequency of SIV than other brain regions in the SIV-infected rhesus macaques of Chinese-origin (chRMs) even on suppressive combination antiretroviral therapy (ART). Since residual HIV/SIV reservoir is associated with inflammation, we characterized the neuroinflammation by gene expression and systemic levels of inflammatory molecules in healthy controls and SIV-infected chRMs with or without ART. CCL2, IL-6, and IFN-γ were significantly reduced in the cerebrospinal fluid (CSF) of animals receiving ART. Moreover, there was a correlation between levels of CCL2 in plasma and CSF, suggesting the potential use of plasma CCL2 as a neuroinflammation biomarker. With higher SIV frequency, the basal ganglia of untreated SIV-infected chRMs showed an upregulation of secreted phosphoprotein 1 (SPP1), which could be an indicator of ongoing neuroinflammation. While ART greatly reduced neuroinflammation in general, proinflammatory genes, such as IL-9, were still significantly upregulated. These results expand our understanding of neuroinflammation and signaling in SIV-infected chRMs on ART, an excellent model to study HIV/SIV persistence in the CNS.

Ipsilesional volume loss of basal ganglia and thalamus is associated with poor hand function after ischemic perinatal stroke

Background Perinatal stroke (PS) is the leading cause of hemiparetic cerebral palsy (CP). Involvement of the corticospinal tract on neonatal magnetic resonance imaging (MRI) is predictive of motor outcome in patients with hemiparetic CP. However, early MRI is not available in patients with delayed presentation of PS and prediction of hemiparesis severity remains a challenge. Aims To evaluate the volumes of the basal ganglia, amygdala, thalamus, and hippocampus following perinatal ischemic stroke in relation to hand motor function in children with a history of PS and to compare the volumes of subcortical structures in children with PS and in healthy controls. Methods Term born PS children with arterial ischemic stroke (AIS) (n = 16) and with periventricular venous infarction (PVI) (n = 18) were recruited from the Estonian Pediatric Stroke Database. MRI was accuired during childhood (4-18 years) and the volumes of the basal ganglia, thalamus, amygdala and hippocampus were calculated. The results of stroke patients were compared to the results of 42 age- and sex-matched healthy controls. Affected hand function was evaluated by Assisting Hand Assessment (AHA) and classified by the Manual Ability Classification System (MACS). Results Compared to the control group, children with AIS had smaller volumes of the ipsi- and contralesional thalami, ipsilesional globus pallidus, nucleus accumbens and hippocampus (p < 0.005). Affected hand function in children with AIS was correlated with smaller ipsilesional thalamus, putamen, globus pallidus, hippocampus, amygdala and contralesional amygdala (r > 0.5; p < 0.05) and larger volume of the contralesional putamen and hippocampus (r < − 0.5; p < 0.05). In children with PVI, size of the ipsilesional caudate nucleus, globus pallidus, thalamus (p ≤ 0.001) and hippocampus (p < 0.03) was smaller compared to controls. Smaller volume of the ipsi- and contralesional thalami and ipsilesional caudate nucleus was correlated with affected hand function (r > 0.55; p < 0.05) in children with PVI. Conclusions Smaller volume of ipsilesional thalamus was associated with poor affected hand function regardless of the perinatal stroke subtype. The pattern of correlation between hand function and volume differences in the other subcortical structures varied between children with PVI and AIS. Evaluation of subcortical structures is important in predicting motor outcome following perinatal stroke.

The Influence of Aging on the Functional Connectivity of the Human Basal Ganglia

Although basal ganglia (BG) are involved in the motor disorders of aged people, the effect of aging on the functional interaction of BG is not well-known. This work was aimed at studying the influence of aging on the functional connectivity of the motor circuit of BG (BGmC). Thirty healthy volunteers were studied (young-group 26.4 ± 5.7 years old; aged-group 63.1 ± 5.8 years old) with a procedure planned to prevent the spurious functional connectivity induced by the closed-loop arrangement of the BGmC. BG showed different functional interactions during the inter-task intervals and when subjects did not perform any voluntary task. Aging induced marked changes in the functional connectivity of the BGmC during these inter-task intervals. The finger movements changed the functional connectivity of the BG, these modifications were also different in the aged-group. Taken together, these data show a marked effect of aging on the functional connectivity of the BGmC, and these effects may be at the basis of the motor handicaps of aged people during the execution of motor-tasks and when they are not performing any voluntary motor task.

Uncertainty-guided learning with scaled prediction errors in the basal ganglia

To accurately predict rewards associated with states or actions, the variability of observations has to be taken into account. In particular, when the observations are noisy, the individual rewards should have less influence on tracking of average reward, and the estimate of the mean reward should be updated to a smaller extent after each observation. However, it is not known how the magnitude of the observation noise might be tracked and used to control prediction updates in the brain reward system. Here, we introduce a new model that uses simple, tractable learning rules that track the mean and standard deviation of reward, and leverages prediction errors scaled by uncertainty as the central feedback signal. We provide a normative analysis, comparing the performance of the new model with that of conventional models in a value tracking task. We find that the new model has an advantage over conventional models when tested across various levels of observation noise. Further, we propose a possible biological implementation of the model in the basal ganglia circuit. The scaled prediction error feedback signal is consistent with experimental findings concerning dopamine prediction error scaling relative to reward magnitude, and the update rules are found to be consistent with many features of striatal plasticity. Our results span across the levels of implementation, algorithm, and computation, and might have important implications for understanding the dopaminergic prediction error signal and its relation to adaptive and effective learning.

Immunological causes of obsessive-compulsive disorder: is it time for the concept of an “autoimmune OCD” subtype?

Obsessive-compulsive disorder (OCD) is a highly disabling mental illness that can be divided into frequent primary and rarer organic secondary forms. Its association with secondary autoimmune triggers was introduced through the discovery of Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal infection (PANDAS) and Pediatric Acute onset Neuropsychiatric Syndrome (PANS). Autoimmune encephalitis and systemic autoimmune diseases or other autoimmune brain diseases, such as multiple sclerosis, have also been reported to sometimes present with obsessive-compulsive symptoms (OCS). Subgroups of patients with OCD show elevated proinflammatory cytokines and autoantibodies against targets that include the basal ganglia. In this conceptual review paper, the clinical manifestations, pathophysiological considerations, diagnostic investigations, and treatment approaches of immune-related secondary OCD are summarized. The novel concept of “autoimmune OCD” is proposed for a small subgroup of OCD patients, and clinical signs based on the PANDAS/PANS criteria and from recent experience with autoimmune encephalitis and autoimmune psychosis are suggested. Red flag signs for “autoimmune OCD” could include (sub)acute onset, unusual age of onset, atypical presentation of OCS with neuropsychiatric features (e.g., disproportionate cognitive deficits) or accompanying neurological symptoms (e.g., movement disorders), autonomic dysfunction, treatment resistance, associations of symptom onset with infections such as group A streptococcus, comorbid autoimmune diseases or malignancies. Clinical investigations may also reveal alterations such as increased levels of anti-basal ganglia or dopamine receptor antibodies or inflammatory changes in the basal ganglia in neuroimaging. Based on these red flag signs, the criteria for a possible, probable, and definite autoimmune OCD subtype are proposed.

Functional connectivity in Parkinson’s disease candidates for deep brain stimulation

This study aimed to identify functional neuroimaging patterns anticipating the clinical indication for deep brain stimulation (DBS) in patients with Parkinson’s disease (PD). A cohort of prospectively recruited patients with PD underwent neurological evaluations and resting-state functional MRI (RS-fMRI) at baseline and annually for 4 years. Patients were divided into two groups: 19 patients eligible for DBS over the follow-up and 41 patients who did not meet the criteria to undergo DBS. Patients selected as candidates for DBS did not undergo surgery at this stage. Sixty age- and sex-matched healthy controls performed baseline evaluations. Graph analysis and connectomics assessed global and local topological network properties and regional functional connectivity at baseline and at each time point. At baseline, network analysis showed a higher mean nodal strength, local efficiency, and clustering coefficient of the occipital areas in candidates for DBS over time relative to controls and patients not eligible for DBS. The occipital hyperconnectivity pattern was confirmed by regional analysis. At baseline, a decreased functional connectivity between basal ganglia and sensorimotor/frontal networks was found in candidates for DBS compared to patients not eligible for surgery. In the longitudinal analysis, patient candidate for DBS showed a progressively decreased topological brain organization and functional connectivity, mainly in the posterior brain networks, and a progressively increased connectivity of basal ganglia network compared to non-candidates for DBS. RS-fMRI may support the clinical indication to DBS and could be useful in predicting which patients would be eligible for DBS in the earlier stages of PD.