Background: Brain sensing devices are approved today for Parkinson's, essential tremor, and epilepsy therapies. Clinical decisions for implants are often influenced by the premise that patients... Show moreBackground: Brain sensing devices are approved today for Parkinson's, essential tremor, and epilepsy therapies. Clinical decisions for implants are often influenced by the premise that patients will benefit from using sensing technology. However, artifacts, such as ECG contamination, can render such treat-ments unreliable. Therefore, clinicians need to understand how surgical decisions may affect artifact probability. Objectives: Investigate neural signal contamination with ECG activity in sensing enabled neuro -stimulation systems, and in particular clinical choices such as implant location that impact signal fidelity. Methods: Electric field modeling and empirical signals from 85 patients were used to investigate the relationship between implant location and ECG contamination. Results: The impact on neural recordings depends on the difference between ECG signal and noise floor of the electrophysiological recording. Empirically, we demonstrate that severe ECG contamination was more than 3.2x higher in left-sided subclavicular implants (48.3%), when compared to right-sided im -plants (15.3%). Cranial implants did not show ECG contamination. Conclusions: Given the relative frequency of corrupted neural signals, we conclude that implant location will impact the ability of brain sensing devices to be used for "closed-loop" algorithms. Clinical ad-justments such as implant location can significantly affect signal integrity and need consideration. (c) 2021 Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/). Show less
Background: Epileptic (absence) seizures in the cerebral cortex can be stopped by pharmacological and optogenetic stimulation of the cerebellar nuclei (CN) neurons that innervate the thalamus.... Show moreBackground: Epileptic (absence) seizures in the cerebral cortex can be stopped by pharmacological and optogenetic stimulation of the cerebellar nuclei (CN) neurons that innervate the thalamus. However, it is unclear how such stimulation can modify underlying thalamo-cortical oscillations. Hypothesis: Here we tested whether rhythmic synchronized thalamo-cortical activity during absence seizures can be desynchronized by single-pulse optogenetic stimulation of CN neurons to stop seizure activity. Methods: We performed simultaneous thalamic single-cell and electrocorticographical recordings in awake tottering mice, a genetic model of absence epilepsy, to investigate the rhythmicity and synchronicity. Furthermore, we tested interictally the impact of single-pulse optogenetic CN stimulation on thalamic and cortical recordings. Results: We show that thalamic firing is highly rhythmic and synchronized with cortical spike-and-wave discharges during absence seizures and that this phase-locked activity can be desynchronized upon single-pulse optogenetic stimulation of CN neurons. Notably, this stimulation of CN neurons was more effective in stopping seizures than direct, focal stimulation of groups of afferents innervating the thalamus. During interictal periods, CN stimulation evoked reliable but heterogeneous responses in thalamic cells in that they could show an increase or decrease in firing rate at various latencies, bi-phasic responses with an initial excitatory and subsequent inhibitory response, or no response at all. Conclusion: Our data indicate that stimulation of CN neurons and their fibers in thalamus evokes differential effects in its downstream pathways and desynchronizes phase-locked thalamic neuronal firing during seizures, revealing a neurobiological mechanism that may explain how cerebellar stimulation can stop seizures. (c) 2021 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND Show less
Warren, C.M.; Tona, K.D.; Ouwerkerk, L.; Paridon, J. van; Poletiek, F.; Steenbergen, H. van; ... ; Nieuwenhuis, S. 2019
BackgroundSubthalamic nucleus (STN) deep brain stimulation effectively improves parkinsonian symptoms. It is hypothesized that distinct functional territories with different neurophysiologic... Show moreBackgroundSubthalamic nucleus (STN) deep brain stimulation effectively improves parkinsonian symptoms. It is hypothesized that distinct functional territories with different neurophysiologic activity within the STN relate to different symptoms.ObjectiveThe aim of the study was to identify distinctive characteristics of STN neuronal activity related to tremor by directly comparing tremor sides with no-tremor sides. In addition, we studied the spatial pattern of frequency distributions within the STN in more detail.MethodsWe analyzed intraoperative STN single/multiunit recordings from 33 tremor sides and 23 no-tremor sides. STN tracks were normalized to a length of 1 and subdivided into eight successive layers. The power spectral density was split into six frequency bands: theta (3-8 Hz), alpha (9-12 Hz), lower beta (13-20 Hz), upper beta (21-30 Hz), lower gamma (31-59 Hz), and upper gamma (60-100 Hz).ResultsTremor sides presented predominant theta frequency oscillations in the most dorsal layers of the STN, whereas in no-tremor sides beta frequencies predominated. Oscillatory activity was stronger in the dorsal STN than in the ventral, and this pattern was specific for frequencies in the theta, alpha, and beta bands, but not in the gamma bands.ConclusionsOur study supports the hypothesis that the presence of tremor is associated with a distinctive neuronal oscillations pattern. In particular, we demonstrate the specificity of the association of theta frequencies in the dorsal STN with tremor. Identification of symptom-specific characteristics of intraoperative microrecordings in the STN may lead to refinement of targeting for each patient, tailored to the specific clinical presentation. (C) 2012 Elsevier Inc. All rights reserved. Show less