Umair Hassan

All Publications

• DLPFC TMS Suppresses High-Frequency Neural Activity in the Human sgACC. Brain stimulation Solomon, E. A., Hassan, U., Trapp, N. T., Boes, A. D., Keller, C. J. 2025

  View details for DOI 10.1016/j.brs.2025.11.012

  View details for PubMedID 41241258

• Noninvasive profiling of input-output excitability curves in human prefrontal cortex. bioRxiv : the preprint server for biology Chen, N. F., Hassan, U., Ross, J. M., Forman, L., Hartford, J. W., Gogulski, J., Parmigiani, S., Truong, J., Keller, C. J., Cline, C. C. 2025

  Abstract

  The human prefrontal cortex plays a critical role in cognitive control and behavior, and its dysfunction has been linked to numerous psychiatric and neurological disorders. However, noninvasive measurement of prefrontal activity remains challenging, limiting our understanding of how to optimize prefrontal treatments. Input-output relationships reveal how neural circuits respond to different inputs and are essential for determining optimal treatment parameters and understanding individual variability in treatment response, yet systematic investigation of prefrontal input-output relationships has been lacking.To characterize human prefrontal excitability with input-output (I/O) curves.We employed transcranial magnetic stimulation (TMS) with electroencephalography in a randomized mixed-block design with 28 healthy participants receiving single-pulse TMS to left dorsolateral prefrontal cortex (dlPFC) across 12 stimulation intensities (60-140% of resting motor threshold). We quantified prefrontal excitability using early local TMS-evoked potentials (EL-TEPs), local cortical responses measured locally 20-60 ms post-stimulus.We observed a strong effect of TMS intensity on prefrontal EL-TEPs. Sigmoidal EL-TEP I/O curves were observed in 57% of participants, with the sigmoidality partially explained by the signal quality of the EL-TEP. Correlations were observed between EL-TEP and motor-evoked potential curve parameters, but intensity parameterization approaches did not significantly differ in explaining inter-individual EL-TEP response variability. Reliable EL-TEPs could be obtained using fewer TMS pulses at higher intensities, and test-retest assessments revealed robust I/O curve profiles.These findings provide a systematic noninvasive characterization of prefrontal input-output physiology in humans, establishing a validated framework for estimating prefrontal excitability. The comparison of various intensity parameterizations motivates the need for enhanced models and individualized measurement of stimulation responses.

  View details for DOI 10.1101/2025.09.26.678876

  View details for PubMedID 41040393

  View details for PubMedCentralID PMC12485743

• A Practical Preprocessing Pipeline for Concurrent TMS-iEEG: Critical Steps and Methodological Considerations. bioRxiv : the preprint server for biology Li, Z., Liu, X., Tatz, J., Hassan, U., Wang, J. B., Keller, C. J., Trapp, N. T., Boes, A. D., Jiang, J. 2025

  Abstract

  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.

  View details for DOI 10.1101/2025.08.13.670238

  View details for PubMedID 40894703

  View details for PubMedCentralID PMC12393282

• Sensory Entrained TMS (seTMS) Enhances Motor Cortex Excitability. Human brain mapping Ross, J. M., Forman, L., Gogulski, J., Hassan, U., Cline, C. C., Parmigiani, S., Truong, J., Hartford, J. W., Chen, N. F., Fujioka, T., Makeig, S., Pascual-Leone, A., Keller, C. J. 2025; 46 (10): e70267

  Abstract

  Transcranial magnetic stimulation (TMS) applied to the motor cortex has revolutionized the study of motor physiology in humans. Despite this, TMS-evoked electrophysiological responses show significant fluctuation, due in part to inconsistencies between TMS pulse timing and ongoing brain oscillations. Small or inconsistent responses to TMS limit mechanistic insights and clinical efficacy, necessitating the development of methods to precisely coordinate the timing of TMS pulses to the phase of relevant oscillatory activity. We introduce Sensory Entrained TMS (seTMS), a novel approach that uses musical rhythms to synchronize brain oscillations and time TMS pulses to enhance cortical excitability. Focusing on the sensorimotor alpha rhythm, a neural oscillation associated with motor cortical inhibition, we examine whether rhythm-evoked sensorimotor alpha phase alignment affects primary motor cortical (M1) excitability in healthy young adults (n = 33). We first confirmed using electroencephalography (EEG) that passive listening to musical rhythms desynchronizes inhibitory sensorimotor brain rhythms (mu oscillations) around 200 ms before auditory rhythmic events (27 participants). We then targeted this optimal time window by delivering single TMS pulses over M1 200 ms before rhythmic auditory events while recording motor-evoked potentials (MEPs; 19 participants), which resulted in significantly larger MEPs compared to standard single pulse TMS and an auditory control condition. Neither EEG measures during passive listening nor seTMS-induced MEP enhancement showed dependence on musical experience or training. These findings demonstrate that seTMS effectively enhances corticomotor excitability and establishes a practical, cost-effective method for optimizing non-invasive brain stimulation outcomes.

  View details for DOI 10.1002/hbm.70267

  View details for PubMedID 40622189

  View details for PubMedCentralID PMC12231655

• Pulsed inhibition of corticospinal excitability by the thalamocortical sleep spindle. Brain stimulation Hassan, U., Okyere, P., Masouleh, M. A., Zrenner, C., Ziemann, U., Bergmann, T. O. 2025

  Abstract

  Thalamocortical sleep spindles, i.e., oscillatory bursts at ∼12-15 Hz of waxing and waning amplitude, are a hallmark feature of non-rapid eye movement (NREM) sleep and believed to play a key role in memory reactivation and consolidation. Generated in the thalamus and projecting to neocortex and hippocampus, they are phasically modulated by neocortical slow oscillations (<1 Hz) and in turn phasically modulate hippocampal sharp-wave ripples (>80 Hz). This hierarchical cross-frequency nesting, where slower oscillations group faster ones into certain excitability phases, may enable phase-dependent plasticity in the neocortex, and spindles have thus been considered windows of plasticity in the sleeping brain. However, the assumed phasic excitability modulation had not yet been demonstrated for spindles. Utilizing a recently developed real-time spindle detection algorithm, we applied spindle phase-triggered transcranial magnetic stimulation (TMS) to the primary motor cortex (M1) hand area to characterize the corticospinal excitability profile of spindles via motor evoked potentials (MEP). MEPs showed net suppression during spindles, driven by a "pulse of inhibition" during its falling flank with no inhibition or facilitation during its peak, rising flank, or trough. This unidirectional ("asymmetric") modulation occurred on top of the general sleep-related inhibition during spindle-free NREM sleep and did not extend into the refractory post-spindle periods. We conclude that spindles exert "asymmetric pulsed inhibition" on corticospinal excitability. These findings and the developed real-time spindle targeting methods enable future studies to investigate the causal role of spindles in phase-dependent synaptic plasticity and systems memory consolidation during sleep by repetitively targeting relevant spindle phases.

  View details for DOI 10.1016/j.brs.2025.02.015

  View details for PubMedID 39986374

• Sensory Entrained TMS (seTMS) enhances motor cortex excitability. bioRxiv : the preprint server for biology Ross, J. M., Forman, L., Gogulski, J., Hassan, U., Cline, C. C., Parmigiani, S., Truong, J., Hartford, J. W., Chen, N. F., Fujioka, T., Makeig, S., Pascual-Leone, A., Keller, C. J. 2024

  Abstract

  Transcranial magnetic stimulation (TMS) applied to the motor cortex has revolutionized the study of motor physiology in humans. Despite this, TMS-evoked electrophysiological responses show significant variability, due in part to inconsistencies between TMS pulse timing and ongoing brain oscillations. Variable responses to TMS limit mechanistic insights and clinical efficacy, necessitating the development of methods to precisely coordinate the timing of TMS pulses to the phase of relevant oscillatory activity. We introduce Sensory Entrained TMS (seTMS), a novel approach that uses musical rhythms to synchronize brain oscillations and time TMS pulses to enhance cortical excitability. Focusing on the sensorimotor alpha rhythm, a neural oscillation associated with motor cortical inhibition, we examine whether rhythm-evoked sensorimotor alpha phase alignment affects primary motor cortical (M1) excitability in healthy young adults (n=33). We first confirmed using electroencephalography (EEG) that passive listening to musical rhythms desynchronizes inhibitory sensorimotor brain rhythms (mu oscillations) around 200 ms before auditory rhythmic events (27 participants). We then targeted this optimal time window by delivering single TMS pulses over M1 200 ms before rhythmic auditory events while recording motor-evoked potentials (MEPs; 19 participants), which resulted in significantly larger MEPs compared to standard single pulse TMS and an auditory control condition. Neither EEG measures during passive listening nor seTMS-induced MEP enhancement showed dependence on musical experience or training. These findings demonstrate that seTMS effectively enhances corticomotor excitability and establishes a practical, cost-effective method for optimizing non-invasive brain stimulation outcomes.

  View details for DOI 10.1101/2024.11.26.625537

  View details for PubMedID 39651225

  View details for PubMedCentralID PMC11623581

• Using real-time EEG-triggered TMS to unravel the corticospinal excitability profile of sleep spindles and the effect of slow oscillation-spindle nesting Groesser, S., Knietsch, K., Breuer, F., Seifpour, S., Grigoreva, A., Hassan, U., Ulf, Z., Himmerich, K., Bergmann, T. WILEY. 2024

  View details for Web of Science ID 001319389403004

• Effects of transcranial magnetic stimulation on the human brain recorded with intracranial electrocorticography. Molecular psychiatry Wang, J. B., Hassan, U., Bruss, J. E., Oya, H., Uitermarkt, B. D., Trapp, N. T., Gander, P. E., Howard, M. A., Keller, C. J., Boes, A. D. 2024

  Abstract

  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 neurophysiological 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 22 neurosurgical participants with no adverse events. We next evaluated intracranial responses to single pulses of TMS to the dorsolateral prefrontal cortex (dlPFC) (N = 10, 1414 electrodes). We demonstrate that TMS is capable of inducing evoked potentials both locally within the dlPFC and in downstream regions functionally connected to the dlPFC, including the anterior cingulate and insular cortex. These downstream effects were not observed when stimulating other distant brain regions. Intracranial dlPFC electrical stimulation had similar timing and downstream effects as TMS. 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.

  View details for DOI 10.1038/s41380-024-02405-y

  View details for PubMedID 38317012

  View details for PubMedCentralID 4876726