Effects of ramped-frequency thalamic deep brain stimulation on tremor and activity of modeled neurons

We conducted intraoperative measurements of tremor to quantify the effects of temporally patterned ramped-frequency DBS trains on tremor.

Seven patterns of stimulation were tested in nine subjects with thalamic DBS for essential tremor: stimulation 'off', three ramped-frequency stimulation (RFS) trains from 130 → 50 Hz, 130 → 60 Hz, and 235 → 90 Hz, and three constant frequency stimulation (CFS) trains at 72, 82, and 130 Hz. The same patterns were applied to a computational model of the thalamic neural network.

Temporally patterned 130 → 60 Hz ramped-frequency trains suppressed tremor relative to stimulation 'off,' but 130 → 50 Hz, 130 → 60 Hz, and 235 → 90 Hz ramped-frequency trains were no more effective than constant frequency stimulation with the same mean interpulse interval (IPI). Computational modeling revealed that rhythmic burst-driver inputs to thalamus were masked during DBS, but long IPIs, concurrent with pauses in afferent cerebellar and cortical firing, allowed propagation of bursting activity. The mean firing rate of bursting-type model neurons as well as the firing pattern entropy of model neurons were both strongly correlated with tremor power across stimulation conditions.

Frequency-ramped DBS produced equivalent tremor suppression as constant frequency thalamic DBS. Tremor-related thalamic burst activity may result from burst-driver input, rather than by an intrinsic rebound mechanism.

Ramping stimulation frequency may exacerbate thalamic burst firing by introducing consecutive pauses of increasing duration to the stimulation pattern.