Developmental neurobiology of cerebellar and Basal Ganglia connections

Abstract

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Nicotinamide Riboside for Ataxia Telangiectasia: A Report of an Early Treated Individual

“…In a recently published open label study 24 AT individuals (mean age 17.5, standard deviation 15 years) showed an improvement of ataxia scores and immunoglobulin levels upon supplementation with 25 mg/kg/day NR during four months, followed by a subsequent decrease during 2 months of NR-withdrawal [3]. In the early childhood, brain and cerebellum are more vulnerable to changes in synaptic transmission, regulation of synaptic plasticity and nervous system development [4,5]. Therefore, earlier treatment could implement more treatment benefits.…”

Dystonia and the pedunculopontine nucleus: Current evidences and potential mechanisms

“…In addition, the cholinergic lesion of the PPN were significantly associated with loss and morphologic changes of nigral dopaminergic neurons, which indirectly affects the dopamine release in the striatum through the nigra-striatum pathway ( 70 ). Meanwhile, patients with dystonia have been reported as hypoactivity at the cerebellar cholinergic terminals at lobules VI and VII that response for the cerebellar sensorimotor projections to the cortex and working memory, which reflects that the abnormal cholinergic input form the PPN to the cerebellum might be related to the impaired sensorimotor integration and cognitive functions in patients of dystonia ( 15 ). Moreover, the cholinergic lesion of the PPN could also descendingly contribute to the disinhibition of the motor neurons and interneurons in the spinal cord, leading to muscle hyperexcitaion and loss of surround inhibition ( 21 ) ( Figure 1B ).…”

“…So far, increasing preclinical evidences also showed alterations of the muscle tone, locomotion, cognitive functions and sleep following lesion or neuromodulation of the PPN, which mimicked the motor and non-motor manifestations of dystonia ( 2 , 5 , 12 – 14 ). Moreover, from the anatomical aspects, the PPN has dense connections with the dystonia-related basal ganglia-cerebello-thalamo-cortical circuit, which lays the foundation of the PPN involved in dystonia ( 15 ).…”

Front and center: Maturational dysregulation of frontal lobe functional neuroanatomic connections in attention deficit hyperactivity disorder

“…The hyperdirect pathway suppresses unwanted movement and it will subsequently inhibit movement once an action has been completed ( Nambu et al, 2002 ; Chen et al, 2020 ). If there exists a motor activity deficit or underdevelopment of this pathway and its connections, overactivity of the premotor loop on the left hemisphere will likely be evidenced ( Singer et al, 2015 ; Dalley and Robbins, 2017 ; Guo et al, 2018 ; Temiz et al, 2020 ; Sival et al, 2022 ), which will, in turn, activate the direct pathway and increase motor activity that can be exemplified by motor tics ( Leisman and Sheldon, 2022 ), or stereotypical movements not infrequently evidenced in hyperkinetic disorders such as ADHD, Tourette’s syndrome, autism spectrum disorder (ASD), etc. ( Melillo and Leisman, 2009 ; Temiz et al, 2020 ; Hannah and Aron, 2021 ).…”