Electroceutically induced subthalamic high-frequency oscillations and evoked compound activity may explain the mechanism of therapeutic stimulation in Parkinson’s disease

Despite having remarkable utility in treating movement disorders, the lack of understanding of the underlying mechanisms of high-frequency deep brain stimulation (DBS) is a main challenge in choosing personalized stimulation parameters. Here we investigate the modulations in local field potentials induced by electrical stimulation of the subthalamic nucleus (STN) at therapeutic and non-therapeutic frequencies in Parkinson’s disease patients undergoing DBS surgery. We find that therapeutic high-frequency stimulation (130–180 Hz) induces high-frequency oscillations (~300 Hz, HFO) similar to those observed with pharmacological treatment. Along with HFOs, we also observed evoked compound activity (ECA) after each stimulation pulse. While ECA was observed in both therapeutic and non-therapeutic (20 Hz) stimulation, the HFOs were induced only with therapeutic frequencies, and the associated ECA were significantly more resonant. The relative degree of enhancement in the HFO power was related to the interaction of stimulation pulse with the phase of ECA. We propose that high-frequency STN-DBS tunes the neural oscillations to their healthy/treated state, similar to pharmacological treatment, and the stimulation frequency to maximize these oscillations can be inferred from the phase of ECA waveforms of individual subjects. The induced HFOs can, therefore, be utilized as a marker of successful re-calibration of the dysfunctional circuit generating PD symptoms.

Modulation of narrowband and broadband gamma connectivity in retinal degeneration mice according to electrical stimulation pulse width

Brain connectivity involves the structural, functional and effective communication between neurons across brain regions and is expressed in neuronal oscillations. Previous research has reported the evidence of two types of gamma oscillations namely the broadband gamma (30 Hz - 90 Hz) and narrowband gamma (55 Hz - 70 Hz) oscillations which have been implicated in excitatory and inhibitory network transmission. There is presently no systematic investigation of the relationship between electrical stimulation pulse width and narrow or broadband gamma oscillations in visual-deficient mice. In the current study, we set out to bridge this gap in knowledge by exploring the modulation of brain connectivity indices in broadband gamma and narrowband gamma oscillations in response to varying electrical stimulation pulse width in retinal degeneration (rd) mice. The results revealed that a low pulse width (0.5 ms/phase) strongly enhances coherence and directional connectivity of broadband and narrowband gamma oscillations in contra visual cortex and contra prefrontal cortex of rd mice. This study serves a crucial role in the design and utilisation of visual prostheses by contributing to the understanding of information transmission between different brain regions under retinal electrical stimulation in visual-deficit population.

Modulation of narrowband and broadband gamma connectivity in retinal degeneration mice according to electrical stimulation pulse width

Brain connectivity involves the structural, functional and effective communication between neurons across brain regions and is expressed in neuronal oscillations. Previous research has reported the evidence of two types of gamma oscillations namely the broadband gamma (30 Hz - 90 Hz) and narrowband gamma (55 Hz - 70 Hz) oscillations which have been implicated in excitatory and inhibitory network transmission. There is presently no systematic investigation of the relationship between electrical stimulation pulse width and narrow or broadband gamma oscillations in visual-deficient mice. In the current study, we set out to bridge this gap in knowledge by exploring the modulation of brain connectivity indices in broadband gamma and narrowband gamma oscillations in response to varying electrical stimulation pulse width in retinal degeneration (rd) mice. The results revealed that a low pulse width (0.5 ms/phase) strongly enhances coherence and directional connectivity of broadband and narrowband gamma oscillations in contra visual cortex and contra prefrontal cortex of rd mice. This study serves a crucial role in the design and utilisation of visual prostheses by contributing to the understanding of information transmission between different brain regions under retinal electrical stimulation in visual-deficit population.

Electroceutically induced subthalamic high frequency oscillations and evoked compound activity may explain the mechanism of therapeutic stimulation in Parkinson's Disease

Despite having remarkable utility in treating movement disorders, the lack of understanding of the underlying mechanisms of high-frequency deep brain stimulation (DBS) is a main challenge in choosing personalized stimulation parameters. Here we investigate the modulations in local field potentials induced by therapeutic and non-therapeutic electrical stimulation of the subthalamic nucleus (STN) in Parkinson’s disease patients undergoing DBS surgery. We find that therapeutic high-frequency stimulation (130-180 Hz) induces high-frequency oscillations (~300 Hz, HFO) similar to those observed with pharmacological treatment. Along with HFOs, we also observed evoked compound activity (ECA) after each stimulation pulse. While ECA was observed in both therapeutic and non-therapeutic (20Hz) stimulation, the HFOs were induced only with therapeutic frequencies and the associated ECA were significantly more resonant. The relative degree of enhancement in the HFO power was related to the interaction of stimulation pulse with the phase of ECA.We propose that high-frequency STN-DBS tunes the neural oscillations to their healthy/treated state, similar to pharmacological treatment, and the stimulation frequency to maximize these oscillations can be inferred from the phase of ECA waveforms of individual subjects. The induced HFOs can, therefore, be utilized as a marker of successful re-calibration of the dysfunctional circuit generating PD symptoms.

ApproXON: Heuristic Approximation to the E-Field-Threshold for Deep Brain Stimulation Volume-of-Tissue-Activated Estimation

This paper introduces a heuristic approximation of the e-field threshold used for volume-of-tissue-activated computation in deep brain stimulation. Pulse width and axon diameter are used as predictors. An open source implementation in MATLAB is provided together with an integration in the open LeadDBS deep brain stimulation research toolbox.