The temporal pattern of stimulation may be important to the mechanism of deep brain stimulation

Abstract

Deep brain stimulation (DBS) has emerged as an important and potentially powerful treatment option for the management of carefully selected patients with advanced Parkinson's disease (PD) who are not adequately controlled by standard medication therapy. Though considerable advances have been made, the mechanisms underlying the therapeutic effects of DBS remain unclear despite its clinical efficacy. It is now widely held that both excitation and inhibition can occur secondary to stimulation, and it is suspected that abnormal synchronized oscillations may also be important in the mechanism of DBS. Other potentially important processes, including blood flow changes, local and upstream neurogenesis, and the modulation of neurotransmitters through stimulation of bordering astrocytes are also being investigated. Recent research has suggested that the temporal pattern of DBS stimulation is also an important variable in DBS neuromodulation, yet the extent of its influence on DBS efficacy has yet to be determined. As high stimulation frequency alone does not appear to be sufficient for optimal symptom suppression, attention to stimulation pattern might lead to more effective symptom control and reduced side effects, possibly at a lower frequency. Stimulation pattern may be potentially amenable to therapeutic modulation and its role in the clinical efficacy of DBS should be addressed through further focus and research.

Keywords: Deep brain stimulation; Frequency; Non-regular; Temporal pattern.

Fig. 1

Schematic of the classical model of the direct and indirect pathways in basal ganglia circuitry. Unfilled arrows are excitatory connections. Filled arrows are inhibitory connections. Grey and italics indicate updates to the classical model. D1=D1 dopaminergic receptors; D2=D2 dopaminergic receptors; GABA=γ-aminobutyric acid (GABA)-ergic; Glu=glutaminergic; GPe=external segment of the globus pallidus; GPi=internal segment of the globus pallidus; SNc=substantia nigra pars compacta; SNr=substantia nigra pars reticulata; STN=subthalamic nucleus; Thal=thalamus.