An electrophysiological perspective on Parkinson’s disease: symptomatic pathogenesis and therapeutic approaches

Journal of Biomedical Science

Cheng-Kai Yang¹  Lan-Hsin Nancy Lee²  Chung-Chin Kuo³  Hsing-Jung Lai⁴  Chen-Syuan Huang⁵  Hsiang-Hao Chuang⁵  Ya-Chin Yang⁶ 

[1] Department of Biomedical Sciences, College of Medicine, Chang Gung University, 259 Wen-Hwa 1st Road, Kwei-Shan, 333, Taoyuan, Taiwan;Department of Physiology, National Taiwan University College of Medicine, 1 Jen-Ai Road, 1st Section, 100, Taipei, Taiwan;Department of Neurology, Fu Jen Catholic University Hospital, New Taipei, Taiwan;Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan;Department of Physiology, National Taiwan University College of Medicine, 1 Jen-Ai Road, 1st Section, 100, Taipei, Taiwan;Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan;Department of Physiology, National Taiwan University College of Medicine, 1 Jen-Ai Road, 1st Section, 100, Taipei, Taiwan;Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan;National Taiwan University Hospital, Jin-Shan Branch, New Taipei, Taiwan;Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan;Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan;Department of Biomedical Sciences, College of Medicine, Chang Gung University, 259 Wen-Hwa 1st Road, Kwei-Shan, 333, Taoyuan, Taiwan;Neuroscience Research Center, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan;

关键词: Basal ganglia circuitry;    Subthalamic nucleus;    Brain rhythms;    Burst discharges;    Cortico-subcortical re-entrant loops;    Brain stimulation;    Hyperdirect pathway;    Hyperkinesia;    Hypokinesia;    Motor control;   

DOI  :  10.1186/s12929-021-00781-z

来源: Springer

【 摘 要 】

Parkinson’s disease (PD), or paralysis agitans, is a common neurodegenerative disease characterized by dopaminergic deprivation in the basal ganglia because of neuronal loss in the substantia nigra pars compacta. Clinically, PD apparently involves both hypokinetic (e.g. akinetic rigidity) and hyperkinetic (e.g. tremor/propulsion) symptoms. The symptomatic pathogenesis, however, has remained elusive. The recent success of deep brain stimulation (DBS) therapy applied to the subthalamic nucleus (STN) or the globus pallidus pars internus indicates that there are essential electrophysiological abnormalities in PD. Consistently, dopamine-deprived STN shows excessive burst discharges. This proves to be a central pathophysiological element causally linked to the locomotor deficits in PD, as maneuvers (such as DBS of different polarities) decreasing and increasing STN burst discharges would decrease and increase the locomotor deficits, respectively. STN bursts are not so autonomous but show a “relay” feature, requiring glutamatergic synaptic inputs from the motor cortex (MC) to develop. In PD, there is an increase in overall MC activities and the corticosubthalamic input is enhanced and contributory to excessive burst discharges in STN. The increase in MC activities may be relevant to the enhanced beta power in local field potentials (LFP) as well as the deranged motor programming at the cortical level in PD. Moreover, MC could not only drive erroneous STN bursts, but also be driven by STN discharges at specific LFP frequencies (~ 4 to 6 Hz) to produce coherent tremulous muscle contractions. In essence, PD may be viewed as a disorder with deranged rhythms in the cortico-subcortical re-entrant loops, manifestly including STN, the major component of the oscillating core, and MC, the origin of the final common descending motor pathways. The configurations of the deranged rhythms may play a determinant role in the symptomatic pathogenesis of PD, and provide insight into the mechanism underlying normal motor control. Therapeutic brain stimulation for PD and relevant disorders should be adaptively exercised with in-depth pathophysiological considerations for each individual patient, and aim at a final normalization of cortical discharge patterns for the best ameliorating effect on the locomotor and even non-motor symptoms.

【 授权许可】

CC BY