Involvement of the Red Nucleus in the Compensation of Parkinsonism may Explain why Primates can develop Stable Parkinson’s Disease

Abstract

Neurological compensatory mechanisms help our brain to adjust to neurodegeneration as in Parkinson’s disease. It is suggested that the compensation of the damaged striato-thalamo-cortical circuit is focused on the intact thalamo-rubro-cerebellar pathway as seen during presymptomatic Parkinson, paradoxical movement and sensorimotor rhythm (SMR). Indeed, the size of the red nucleus, connecting the cerebellum with the cerebral cortex, is larger in Parkinson’s disease patients suggesting an increased activation of this brain area. Therefore, the red nucleus was examined in MPTP-induced parkinsonian marmoset monkeys during the presymptomatic stage and after SMR activation by neurofeedback training. We found a reverse significant correlation between the early expression of parkinsonian signs and the size of the parvocellular part of the red nucleus, which is predominantly present in human and non-human primates. In quadrupedal animals it consists mainly of the magnocellular part. Furthermore, SMR activation, that mitigated parkinsonian signs, further increased the size of the red nucleus in the marmoset monkey. This plasticity of the brain helps to compensate for dysfunctional movement control and can be a promising target for compensatory treatment with neurofeedback technology, vibrotactile stimulation or DBS in order to improve the quality of life for Parkinson’s disease patients.

Advances in Electrical Neuroimaging, Brain Networks and Neurofeedback Protocols

“…This means that in 2019 one can reinforce deep non-dopamine cerebellar and red nucleus circuits that may reduce Parksonism. As demonstrated by Philippens & Vanwersch [100] and Philippens et al, [101] in monkeys and in studies using the scalp surface EEG SMR which is also directly effects the non-dopamine and non-damaged cerebellar compensatory circuits Thompson & Thompson [102].…”

“…SMR EEG neurofeedback (12-15 Hz) reduced parkinsonism symptoms were attributed to reinforcing the cerebellum circuits that do not involve dopamine and are a separate and compensatory motor system involved with gait and long movements and legs as one walks. Importantly, the studies of Philippens & Vanwersch [100] and Philippens et al, [101] demonstrated a red nucleus change in synaptic number and organization in the EEG SMR group. The red nucleus is a relay nucleus from the cerebellum the thalamus to motor cortex circuits, with minimal dopamine involved.…”

“…Monkey studies of chemically induced Parkinsonism and Cz scalp SMR EEG biofeedback demonstrated reduced Parkinsonism that increased synaptic density and synaptic change in the red nucleus in the SMR group. There were two groups: 1-Dopamine degeneration + SMR and 2-Dopamine degeneration + sham SMR [100,101].…”

“…Robert W. Thatcher 1 *, Carl J. Biver 2 , Ernesto Palermero Soler 2 , Joel Lubar 2 and J. Lucas Koberda 3 1 EEG and NeuroImaging Laboratory, Applied Neuroscience Research Institute, St. Petersburg, FL, USA 2 Southeastern Neurofeedback Institute, Pompano Beach, FL, USA 3 Neurology, PL/Brain Enhancement Inc., Tallahassee, FL, USA *Address all correspondence to: rwthatcher@yahoo.com [100,101]. People over age 65 are prone to having balance problems and there are about 40 million Americans older than age 65.…”

Early red nucleus atrophy in relapse‐onset multiple sclerosis

“…Indeed, RN volume was increased in patients with Parkinson's disease and significantly correlated with disease duration and severity, suggesting a compensatory activation of this nucleus (Colpan & Slavin, 2010), probably aimed at compensating the impaired function of the extra‐pyramidal network. Moreover, in nonhuman primates (Philippens, Wubben, Franke, Hofman, & Langermans, 2019) larger RN volume inversely associated with the severity of extra‐pyramidal symptoms. Finally, a damaged striato‐thalamo‐cortical pathway was found to result in a compensatory increase in RN activation (Philippens et al, 2019).…”