Dataset Information

Evoked potentials reveal neural circuits engaged by human deep brain stimulation.

ABSTRACT:

Background

Deep brain stimulation (DBS) is an effective therapy for reducing the motor symptoms of Parkinson's disease, but the mechanisms of action of DBS and neural correlates of symptoms remain unknown.

Objective

To use the neural response to DBS to reveal connectivity of neural circuits and interactions between groups of neurons as potential mechanisms for DBS.

Methods

We recorded activity evoked by DBS of the subthalamic nucleus (STN) in humans with Parkinson's disease. In follow up experiments we also simultaneously recorded activity in the contralateral STN or the ipsilateral globus pallidus from both internal (GPi) and external (GPe) segments.

Results

DBS local evoked potentials (DLEPs) were stereotyped across subjects, and a biophysical model of reciprocal connections between the STN and the GPe recreated DLEPs. Simultaneous STN and GP recordings during STN DBS demonstrate that DBS evoked potentials were present throughout the basal ganglia and confirmed that DLEPs arose from the reciprocal connections between the STN and GPe. The shape and amplitude of the DLEPs were dependent on the frequency and duration of DBS and were correlated with resting beta band oscillations. In the frequency domain, DLEPs appeared as a 350 Hz high frequency oscillation (HFO) independent of the frequency of DBS.

Conclusions

DBS evoked potentials suggest that the intrinsic dynamics of the STN and GP are highly interlinked and may provide a promising new biomarker for adaptive DBS.

SUBMITTER: Schmidt SL

PROVIDER: S-EPMC7722102 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Deep brain stimulation is an established therapy for Parkinson's disease; however, its effectiveness is hindered by limited understanding of therapeutic mechanisms and the lack of a robust feedback signal for tailoring stimulation. We recently reported that subthalamic nucleus deep brain stimulation evokes a neural response resembling a decaying high-frequency (200-500?Hz) oscillation that typically has a duration of at least 10?ms and is localizable to the dorsal sub-region. As the morphology of this response suggests a propensity for the underlying neural circuitry to oscillate at a particular frequency, we have named it evoked resonant neural activity. Here, we determine whether this evoked activity is modulated by therapeutic stimulation - a critical attribute of a feedback signal. Furthermore, we investigated whether any related changes occurred in spontaneous local field potentials. Evoked and spontaneous neural activity was intraoperatively recorded from 19 subthalamic nuclei in patients with Parkinson's disease. Recordings were obtained before therapeutic stimulation and during 130?Hz stimulation at increasing amplitudes (0.67-3.38?mA), 'washout' of therapeutic effects, and non-therapeutic 20?Hz stimulation. Therapeutic efficacy was assessed using clinical bradykinesia and rigidity scores. The frequency and amplitude of evoked resonant neural activity varied with the level of 130?Hz stimulation (p?<?.001). This modulation coincided with improvement in bradykinesia and rigidity (p?<?.001), and correlated with spontaneous beta band suppression (p?<?.001). Evoked neural activity occupied a similar frequency band to spontaneous high-frequency oscillations (200-400?Hz), both of which decreased to around twice the 130?Hz stimulation rate. Non-therapeutic stimulation at 20?Hz evoked, but did not modulate, resonant activity. These results indicate that therapeutic deep brain stimulation alters the frequency of evoked and spontaneous oscillations recorded in the subthalamic nucleus that are likely generated by loops within the cortico-basal ganglia-thalamo-cortical network. Evoked resonant neural activity therefore has potential as a tool for providing insight into brain network function and has key attributes of a dynamic feedback signal for optimizing therapy.