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Keller, C. J.

Publications and source records attributed to Keller, C. J..

22 records · Page 2Linked to original sources

Mapping cortical excitability in the human dorsolateral prefrontal cortex

ObjectiveTo characterize early TEPs anatomically and temporally (20-50 ms) close to the TMS pulse (EL-TEPs), as well as associated muscle artifacts (<20 ms), across the dlPFC. We hypothesized that TMS location and angle influence EL-TEPs, and that EL-TEP amplitude is inversely related to muscle artifact. Additionally, we sought to determine an optimal group-level TMS target and angle, while investigating the potential benefits of a personalized approach. MethodsIn 16 healthy participants, we applied single-pulse TMS to six targets within the dlPFC at two coil angles and measured EEG responses. ResultsStimulation location significantly influenced EL-TEPs, with posterior and medial targets yielding larger EL-TEPs. Regions with high EL-TEP amplitude had less muscle artifact, and vice versa. The best group-level target yielded 102% larger EL-TEP responses compared to other dlPFC targets. Optimal dlPFC target differed across subjects, suggesting that a personalized targeting approach might boost the EL-TEP by an additional 36%. SignificanceEarly local TMS-evoked potentials (EL-TEPs) can be probed without significant muscle-related confounds in posterior-medial regions of the dlPFC. The identification of an optimal group-level target and the potential for further refinement through personalized targeting hold significant implications for optimizing depression treatment protocols. HighlightsO_LIEarly local TMS-evoked potentials (EL-TEPs) varied significantly across the dlPFC as a function of TMS target. C_LIO_LITMS targets with less muscle artifact had significantly larger EL-TEPs. C_LIO_LISelection of a postero-medial target increased EL-TEPs by 102% compared to anterior targets. C_LI

neuroscience↗

Experimental Suppression of TMS-EEG Sensory Potentials

BackgroundThe sensory experience of transcranial magnetic stimulation (TMS) evokes cortical responses measured in EEG that confound interpretation of TMS-evoked potentials (TEPs). Methods for sensory masking have been proposed to minimize sensory contributions to the TEP, but the most effective combination for suprathreshold TMS to dorsolateral prefrontal cortex (dlPFC) is unknown. ObjectiveWe applied sensory suppression techniques and quantified electrophysiology and perception from suprathreshold dlPFC TMS to identify the best combination to minimize the sensory TEP. MethodsIn 21 healthy adults, we applied single pulse TMS at 120% resting motor threshold (rMT) to the left dlPFC and compared EEG vertex N100-P200 and perception. Conditions included three protocols: No masking (no auditory masking, no foam, jittered inter-stimulus interval (ISI)), Standard masking (auditory noise, foam, jittered ISI), and our ATTENUATE protocol (auditory noise, foam, over-the-ear protection, unjittered ISI). ResultsATTENUATE reduced vertex N100-P200 by 56%, "click" loudness perception by 50%, and scalp sensation by 36%. We show that sensory prediction, induced with predictable ISI, has a suppressive effect on vertex N100-P200, and that combining standard suppression protocols with sensory prediction provides the best N100-P200 suppression. ATTENUATE was more effective than Standard masking, which only reduced vertex N100-P200 by 22%, loudness by 27%, and scalp sensation by 24%. ConclusionsWe introduce a sensory suppression protocol superior to Standard masking and demonstrate that using an unjittered ISI can contribute to minimizing sensory confounds. ATTENUATE provides superior sensory suppression to increase TEP signal-to-noise and contributes to a growing understanding of TMS-EEG sensory neuroscience. HighlightsO_LIATTENUATE is a novel sensory suppression protocol for suprathreshold dlPFC TMS C_LIO_LIATTENUATE is superior to standard masking for minimizing sensory confounds C_LIO_LIATTENUATE reduced vertex N100-P200 by 56% with no effect on the early TEP C_LIO_LIATTENUATE reduced "click" loudness rating by 50% and scalp sensation by 36% C_LIO_LIIndividual modifications are not sufficient to reduce vertex N100-P200 or perception C_LI

neuroscience↗

Effects of transcranial magnetic stimulation on the human brain recorded with intracranial electrocorticography: First-in-human study

Transcranial magnetic stimulation (TMS) is increasingly used as a noninvasive technique for neuromodulation in research and clinical applications, yet its mechanisms are not well understood. Here, we present the first in-human study evaluating the effects of TMS using intracranial electrocorticography (iEEG) in neurosurgical patients. We first evaluated safety in a gel-based phantom. We then performed TMS-iEEG in 20 neurosurgical participants with no adverse events. Next, we evaluated brain-wide intracranial responses to single pulses of TMS to the dorsolateral prefrontal cortex (dlPFC) (N=10, 1414 electrodes). We demonstrate that TMS preferentially induces neuronal responses locally within the dlPFC at sites with higher electric field strength. Evoked responses were also noted downstream in the anterior cingulate and anterior insular cortex, regions functionally connected to the dlPFC. These findings support the safety and promise of TMS-iEEG in humans to examine local and network-level effects of TMS with higher spatiotemporal resolution than currently available methods.

neuroscience↗

Intracortical dynamics underlying repetitive stimulation predicts changes in network connectivity

Targeted stimulation can be used to modulate the activity of brain networks. Previously we demonstrated that direct electrical stimulation produces predictable post-stimulation changes in brain excitability. However, understanding the neural dynamics during stimulation and its relationship to post-stimulation effects is limited but critical for treatment optimization. Here, we applied 10Hz direct electrical stimulation across several cortical regions in 14 patients implanted with intracranial electrodes for seizure monitoring. The stimulation train was characterized by a consistent increase in high gamma (70-170Hz) power. Immediately post-train, low-frequency (1-8Hz) power increased, resulting in an evoked response that was highly correlated with the neural response during stimulation. Using two measures of network connectivity, cortico-cortical evoked potentials (indexing effective connectivity) and theta coherence (indexing functional connectivity), we found a stronger response to stimulation in regions that were highly connected to the stimulation site. In these regions, repeated cycles of stimulation trains and rest progressively altered the stimulation response. Finally, after just 2 minutes (10%) of repetitive stimulation, we were able to predict post-stimulation connectivity changes with high discriminability. Taken together, this work reveals a relationship between stimulation dynamics and post-stimulation connectivity changes in humans. Thus, measuring neural activity during stimulation can inform future plasticity-inducing protocols.

neuroscience↗