Frequency matters: beta‐band subthalamic nucleus deep‐brain stimulation induces Parkinsonian‐like blink abnormalities in normal rats

Abstract

The synchronized beta band oscillations in the basal ganglia-cortical networks in Parkinson's disease (PD) may be responsible for PD motor symptoms or an epiphenomenon of dopamine loss. We investigated the causal role of beta band activity in PD motor symptoms by testing the effects of beta frequency subthalamic nucleus deep brain stimulation (STN DBS) on blink reflex excitability, amplitude, and plasticity in normal rats. Delivering 16 Hz STN DBS produced the same increase in blink reflex excitability and impairment in blink reflex plasticity in normal rats as occurs in rats with 6-OHDA lesions and PD patients. These deficits were not an artifact of STN DBS because when these normal rats received 130 Hz STN DBS, their blink characteristics were the same as without STN DBS. To demonstrate the blink reflex disturbances with 16 Hz STN DBS were frequency specific, we tested the same rats with 7 Hz STN DBS, a theta band frequency typical of dystonia. In contrast to beta stimulation, 7 Hz DBS exaggerated blink reflex plasticity as occurs in focal dystonia. Thus, without destroying dopamine neurons or blocking dopamine receptors, frequency specific STN DBS can be used to create PD- or dystonic-like symptoms in a normal rat.

Subthalamic low-frequency oscillations predict vulnerability to cocaine addiction

“…Our present and previous work has emphasized the therapeutic potential of STN DBS for the treatment of addiction but has also indicated that the frequency used has to be carefully chosen in order to achieve beneficial outcomes and avoid deleterious effects, as described in PD. In rodents and nonhuman primates, low-frequency stimulations drive STN neurons' activity both in vitro and in vivo (52)(53)(54), which would then alter STN output structure activities to promote or worsen PD-like motor symptoms in preclinical and clinical studies (55)(56)(57)(58). In contrast, high-frequency STN DBS is thought to produce its beneficial effect through inactivation of the STN neurons but also antidromic activation of cortical motor neuron in rodent PD models (51,58).…”

Error Analysis and Some Suggestions on Animal Stereotactic Experiment from Inaccuracy of Rhesus Macaques Atlas

“…A lot of articles did not stress the pathology examination after experiments and few of them provided the proof of the position accuracy, which could be a potential cause for great deviation, so the data may not be authentic. [ 6 7 ] Considering the current situation, we conclude some factors that may influence the accuracy of the coordinate.…”

Motor behaviors in the sheep evoked by electrical stimulation of the subthalamic nucleus

“…Lowfrequency (23 Hz) STN stimulation in normal rodents and NHPs can also evoke movements similar to human tremor and dyskinesia [96]. Furthermore, low-(7 or 16 Hz) but not highfrequency (130 Hz) stimulation in normal rodents can also evoke similar eye-blink and EMG abnormalities as observed in human dystonia and PD patients [97]. …”