Deep brain stimulation creates an informational lesion of the stimulated nucleus

Abstract

Deep brain stimulation (DBS) is an effective treatment for movement disorders, but the mechanisms are unclear. DBS generates inhibition of neurons surrounding the electrode while simultaneously activating the output axons of local neurons. This dual effect does not explain two hallmarks of DBS effectiveness: symptom relief is dependent on using a sufficiently high-stimulation frequency, and clinical effects are analogous to those produced by lesion. The effect of DBS at different frequencies on the output of intrinsically active neurons was studied using computational models. DBS produced frequency-dependent modulation of the variability of neuronal output, and above a critical frequency stimulation resulted in regular output with zero variance. The resulting loss of information offers an explanation for the two hallmarks of DBS effectiveness.

Mechanisms and Targets of Deep Brain Stimulation in Movement Disorders

“…The resulting 'informational lesion' may thus prevent pathological activity from being transmitted and amplified within the sensorimotor network. 77 Analysis of DBS experimental data supports the concept that neural pattern, rather than firing rate, is an important determinant of the pathologic state and the therapeutic effects seen with DBS. 37,74,75,85 In addition to changes in mean rate and irregularity of neuronal discharge in the basal ganglia, certain movement disorders are also characterized by the development of rhythmic, oscillatory activity.…”

Deep Brain Stimulation for Movement Disorders of Basal Ganglia Origin: Restoring Function or Functionality?

“…Axons are known to be more sensitive to stimulation than cell bodies [276,277,[281][282][283], so that highfrequency DBS may alter the activity of axons emerging from a given area (this was specifically shown for STN and GPe DBS [283,284]), thus leading to a functional blockade of transmission of information, whether pathological or normal, through the stimulated area, but without silencing of the tissue. This effect is summarized in the term Binformational lesion [ 285]. The concept that DBS produces an informational lesion provided an explanation for the fact that DBS is equally effective for a variety of hypo-and hyperkinetic disorders.…”

Mechanisms of Deep Brain Stimulation in Movement Disorders as Revealed by Changes in Stimulus Frequency

“…HFS in the internal segment of GPi of healthy monkeys reduced the firing rate of 77% of recorded thalamic cells, an inhibitory Coefficient of variation of the instantaneous firing rates from a bursting thalamocortical model neuron as a function of the frequency of extracellular stimulation. Reproduced with permission from Grill et al 16 target of GPi axons, suggesting activation of GPi efferent fibers. 26 HFS in the STN of Parkinsonian monkeys increased the firing rates in the external segment of globus pallidus (GPe) and GPi, excitatory targets of the STN, suggesting activation of STN efferent fibers.…”

“…59 High-frequency (Ͼ70 Hz) STN DBS reduced pallidal beta oscillations (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) in PD subjects in a manner similar to the administration of dopamine precursors, whereas 25 Hz DBS increased the power of pallidal beta oscillations. 60 In addition, high-frequency STN DBS at 130 Hz or 185 Hz attenuated STN beta oscillations in subjects with PD during the period just after DBS was turned off.…”