Biology subjects

Trapp, N. T.

Publications and source records attributed to Trapp, N. T..

10 recordsLinked to original sources

bioRxiv2026

Transcranial magnetic stimulation to the dorsolateral prefrontal cortex modulates single-neuron activity in humans

Transcranial magnetic stimulation (TMS) to the dorsolateral prefrontal cortex (dlPFC) is an FDA-cleared treatment for depression, yet how cortical stimulation influences single neurons in deep brain circuits remains unknown. Using intracranial microelectrode recordings in four neurosurgical patients, we resolved single-neuron spikes as early as 8 ms from 185 single neurons after single-pulse left dlPFC TMS. TMS elicited time-locked firing responses in 46% of neurons across deep cortical and subcortical structures bilaterally. TMS facilitated putative interneuron spiking in striato-thalamic regions from [~]8 ms, peaking at [~]80-100 ms, and lasting to [~]1000 ms, while suppressing putative pyramidal cell spiking with a delayed and slower time course. Trial-by-trial single-neuron modulations were positively correlated with cortico-striato-thalamic network activity and anti-correlated with limbic network activity. These findings reveal that dlPFC TMS facilitates inhibitory firing in executive control networks while suppressing limbic excitatory drive, providing a cellular mechanism for how cortical stimulation modulates distributed brain networks.

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bioRxiv2025

A Practical Preprocessing Pipeline for Concurrent TMS-iEEG: Critical Steps and Methodological Considerations

Transcranial magnetic stimulation combined with intracranial EEG (TMS-iEEG) has emerged as a powerful approach for probing the causal organization and dynamics of the human brain. Despite its promise, the presence of TMS-induced artifacts poses significant challenges for accurately characterizing and interpreting evoked neural responses. In this study, we present a practical preprocessing pipeline for single pulse TMS-iEEG data, incorporating key steps of re-referencing, filtering, artifact interpolation, and detrending. Using both real and simulated data, we systematically evaluated the effects of each step and compared alternative methodological choices. Our results demonstrate that this pipeline effectively attenuated various types of artifacts and noise, yielding cleaner signals for the subsequent analysis of intracranial TMS-evoked potentials (iTEPs). Moreover, we showed that methodological choices can substantially influence iTEPs outcomes. In particular, referencing methods might strongly affect iTEP morphology and amplitude, underscoring the importance of tailoring the referencing strategy to specific signal characteristics and research objectives. For filtering, we recommend a segment-based strategy, i.e., applying filters to data segments excluding the artifact window, to minimize distortion from abrupt TMS-related transients. Overall, this work represents an important step toward establishing a general preprocessing framework for TMS-iEEG data. We hope it encourages broader adoption and methodological development in concurrent TMS-iEEG research, ultimately advancing our understanding of brain organization and TMS mechanisms. HighlightsO_LIWe presented a practical preprocessing pipeline for single pulse TMS-iEEG data, incorporating key steps of re-referencing, filtering, artifact interpolation, and detrending. C_LIO_LIThe pipeline effectively attenuates multiple types of artifacts and noise, enabling accurate characterization of evoked neural responses. C_LIO_LIMethodological alternatives for each preprocessing step were evaluated using real and/or simulated datasets. C_LIO_LIRe-referencing substantially affects the morphology and amplitude of intracranial TMS-evoked potentials and requires careful consideration. C_LIO_LIA segment-based filtering strategy is recommended to better minimize distortion from TMS-related artifacts. C_LI

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bioRxiv2025

Multimodal Evidence for Hippocampal Engagement and Modulation by Functional Connectivity-Guided Parietal TMS

Hippocampal activity supports memory and many other brain functions. Transcranial magnetic stimulation (TMS) guided by hippocampal functional connectivity (FC) shows promise in improving memory, but direct neural evidence of its capacity to engage and modulate hippocampal activity is lacking. Here we combined TMS with intracranial electroencephalography (iEEG) in 8 neurosurgical patients and with functional magnetic resonance imaging (fMRI) in 79 neurologically healthy participants. We identified that (1) single-pulse TMS to individualized parietal cortex guided by hippocampal-FC preferentially evoked distinct temporal and spectral activity patterns in the hippocampus, (2) variability in TMS-evoked hippocampal responses related to individual differences in parietal-hippocampus FC strength, and (3) repetitive TMS to hippocampal-FC-guided parietal cortex selectively suppressed hippocampal theta oscillations. These findings provide multimodal causal neural evidence and important mechanistic insights supporting the development of personalized neuromodulation strategies aimed at improving hippocampus-dependent functions.

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bioRxiv2025

DLPFC Stimulation Suppresses High-Frequency Neural Activity in the Human sgACC

Transcranial magnetic stimulation (TMS) to the dorsolateral prefrontal cortex (DLPFC) is hypothesized to relieve symptoms of depression by inhibiting activity in the subgenual anterior cingulate cortex (sgACC). However, we have a limited understanding of how TMS influences neural activity in the sgACC, owing to its deep location within the brain. To better understand the mechanism of antidepressant response to TMS, we recruited two neurosurgical patients with indwelling electrodes and delivered TMS pulses to the DLPFC while simultaneously recording local field potentials from the sgACC. Spectral analysis revealed a decrease in high-frequency activity (HFA; 70-180 Hz) after each stimulation pulse, which was especially pronounced in the sgACC relative to other regions. TMS-evoked HFA power was generally anticorrelated between the DLPFC and sgACC, even while low-frequency phase locking between the two regions was enhanced. Together, these findings support the notion that TMS to the DLPFC can suppress neural firing in the sgACC, suggesting a possible mechanism by which this treatment regulates mood.

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bioRxiv2024

Dorsolateral prefrontal cortex TMS evokes responses in the subgenual anterior cingulate cortex: Evidence from human intracranial EEG

Transcranial magnetic stimulation combined with intracranial local field potential recordings in humans (TMS-iEEG) represents a new method for investigating electrophysiologic effects of TMS with spatiotemporal precision. We applied TMS-iEEG to the dorsolateral prefrontal cortex (dlPFC) in two subjects and demonstrate evoked activity in the subgenual anterior cingulate cortex (sgACC). This study provides direct electrophysiologic evidence that dlPFC TMS, as targeted for depression treatment, can modulate brain activity in the sgACC.

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bioRxiv2023

TMS provokes target-dependent intracranial rhythms across human cortical and subcortical sites

Transcranial magnetic stimulation (TMS) is increasingly deployed in the treatment of neuropsychiatric illness, under the presumption that stimulation of specific cortical targets can alter ongoing neural activity and cause circuit-level changes in brain function. While the electrophysiological effects of TMS have been extensively studied with scalp electroencephalography (EEG), this approach is most useful for evaluating low-frequency neural activity at the cortical surface. As such, little is known about how TMS perturbs rhythmic activity among deeper structures - such as the hippocampus and amygdala - and whether stimulation can alter higher-frequency oscillations. Recent work has established that TMS can be safely used in patients with intracranial electrodes (iEEG), allowing for direct neural recordings at sufficient spatiotemporal resolution to examine localized oscillatory responses across the frequency spectrum. To that end, we recruited 17 neurosurgical patients with indwelling electrodes and recorded neural activity while patients underwent repeated trials of single-pulse TMS at several cortical sites. Stimulation to the dorsolateral prefrontal cortex (DLPFC) drove widespread low-frequency increases (3-8Hz) in frontolimbic cortices, as well as high-frequency decreases (30-110Hz) in frontotemporal areas, including the hippocampus. Stimulation to parietal cortex specifically provoked low-frequency responses in the medial temporal lobe. While most low-frequency activity was consistent with brief evoked responses, anterior frontal regions exhibited induced theta oscillations following DLPFC stimulation. Taken together, we established that non-invasive stimulation can (1) provoke a mixture of low-frequency evoked power and induced theta oscillations and (2) suppress high-frequency activity in deeper brain structures not directly accessed by stimulation itself.

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bioRxiv2022

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.

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bioRxiv2021

Individualized precision targeting of dorsal attention and default mode networks with rTMS in traumatic brain injury-associated depression

BackgroundAt the group level, antidepressant efficacy of rTMS targets is inversely related to their normative connectivity with subgenual anterior cingulate cortex (sgACC). Individualized connectivity may yield better targets, particularly in patients with neuropsychiatric disorders who may have aberrant connectivity. However, sgACC connectivity shows poor test-retest reliability at the individual level. Individualized resting-state network mapping (RSNM) can reliably map inter-individual variability in brain network organization. ObjectiveTo identify individualized RSNM-based rTMS targets that reliably target the sgACC connectivity profile. MethodsWe used RSNM to identify network-based rTMS targets in 10 healthy controls and 13 individuals with traumatic brain injury-associated depression (TBI-D). These "RSNM targets" were compared with consensus structural targets and targets based on individualized anti-correlation with a group-mean-derived sgACC region ("anti-group-mean sgACC targets"). The TBI-D cohort was randomized to receive active (n=9) or sham (n=4) rTMS to RSNM targets. ResultsThe group-mean sgACC connectivity profile was reliably estimated by individualized correlation with default mode network (DMN) and anti-correlation with dorsal attention network (DAN). Individualized RSNM targets were then identified based on DAN anti-correlation and DMN correlation. Counterintuitively, anti-correlation with the group-mean sgACC connectivity profile was stronger and more reliable for RSNM-derived targets than for "anti-group-mean sgACC targets". Improvement in depression after RSNM-targeted rTMS was predicted by target anti-correlation with the portions of sgACC. Active treatment led to increased connectivity within and between several relevant regions. ConclusionsRSNM may enable reliable individualized rTMS targeting, although further research is needed to determine whether this personalized approach can improve clinical outcomes.

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bioRxiv2017

rTMS with individualized resting-state network mapping for neuropsychiatric sequelae of repetitive traumatic brain injury in a retired NFL player

The recent advent of individualized resting-state network mapping (RSNM) has revealed substantial inter-individual variability in anatomical localization of brain networks identified using resting-state functional MRI (rsfMRI). Such variability may be particularly important after repetitive traumatic brain injury (TBI), which is associated with treatment-resistant depression. RSNM enables personalized targeting of repetitive transcranial magnetic stimulation (rTMS), a focal brain stimulation technique that relieves depression when administered over dorsolateral prefrontal cortex.\n\nRSNM was used to identify left/right dorsolateral prefrontal rTMS targets with maximal difference between dorsal attention network and default mode network (DMN) correlations. These targets were spatially distinct from those identified by prior methods. The method was evaluated by administering twenty sessions of left-sided excitatory and right-sided inhibitory rTMS to a retired NFL defensive lineman with progressive treatment-resistant neuropsychiatric disturbances. Treatment led to improvement in Montgomery-Asberg Depression Rating Scale (72%), cognitive testing, and headache scales. In comparison with healthy individuals and subjects with TBI-associated depression, baseline rsfMRI revealed substantially elevated DMN connectivity with medial temporal lobe (MTL). Serial rsfMRI scans showed gradual improvement in MTL-DMN connectivity and stimulation site connectivity with subgenual anterior cingulate cortex. This highlights the possibility of individualized neuromodulation and biomarker-based monitoring for neuropsychiatric sequelae of repetitive TBI.

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bioRxiv2017

Mapping Movement, Mood, Motivation, and Mentation in the Subthalamic Nucleus

The anatomical connections of the subthalamic nucleus (STN) have driven hypotheses about its functional anatomy, including the hypothesis that the precise anatomical location of STN deep brain stimulation (DBS) determines the variability of motor and non-motor responses across Parkinson disease (PD) patients. We previously tested that hypothesis using a three-dimensional (3D) statistical method to interpret the acute effects of unilateral DBS at each patients clinically optimized DBS settings and active contact. Here we report a similar analysis from a new study in which DBS parameters were standardized and DBS locations were chosen blind to clinical response. In 74 individuals with PD and STN DBS, STN contacts were selected near the dorsal and ventral border of the STN contralateral to the more affected side of the body. Participants were tested off PD medications in each of 3 conditions (ventral STN DBS, dorsal STN DBS and DBS off) for acute effects on mood, apathy, working memory, response inhibition and motor function. Voltage, frequency, and pulse width were standardized, and participants and raters were blind to condition. In a categorical analysis, both dorsal and ventral STN DBS improved mean motor function without affecting cognitive measures. Dorsal STN DBS induced greater improvement in rigidity than ventral STN DBS, whereas ventral STN DBS was more effective for improving anxiety and mood. In the 3D analysis, contact location was significant only for bradykinesia and resting tremor, with the greatest improvement occurring with DBS in dorsal STN and zona incerta. These results provide new, direct functional evidence for the anatomically-derived model of STN using the novel 3D analysis, in which motor function is most represented in dorsal STN. However, our data suggest that functional segregation between motor and non-motor areas of the STN is limited, since locations that induced improvements in motor function and mood overlapped substantially.

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