Brain stimulation in Huntington’s disease

Written by Hartmann CJ, Groiss SJ, Vvesper J, Schnitzler A, Wojtecki L

Huntington’s disease (HD) is a hereditary neurodegenerative disorder which is associated with severe disturbances of motor function, especially choreatic movements, cognitive decline and psychiatric symptoms. Various brain stimulation methods have been used to study brain function in patients with HD. Moreover, brain stimulation has evolved as an alternative or additive treatment option, besides current symptomatic medical treatment. This article summarizes the results of brain stimulation to better understand the characteristics of cortical excitability and plasticity in HD and gives a perspective on the therapeutic role for noninvasive and invasive neuromodulatory brain stimulation methods.
Huntington’s disease (HD) is an autosomal dominant inherited neurodegenerative disorder caused by an expanded CAG repeat in the HTT gene, which leads to progressive impairment of motor function, psychiatric symptoms and cognitive decline [1]. Following mechanisms potentially underlying the disease are currently discussed:

  • Impairment of axonal transport and mitochondrial function [2];

  • Excitotoxic neuronal death due to pathological activity of NMDA-type glutamate receptors [3]; and

  • Aggregation of ubiquitinated huntingtin and transcriptional dysregulation [4].

While cellular pathology can be found throughout the whole body, selective degeneration of medium spiny neurons in the striatum predominantly mediates motor abnormalities [5]. Chorea predominates the motor impairment in the early stage of HD possibly due to disinhibition of the thalamocortical circuitry, a consequence of degeneration of striatal neurons projecting to the indirect pathway of the basal ganglia circuitry [6] and subsequent decreased basal ganglia output [7]. However, deterioration of the direct pathway of the basal ganglia loop and neurodegeneration of other brain areas, which are important for motor control like substantia nigra or cerebral cortex, may also cause dystonia or hypokinetic-rigid symptoms [8,9].

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