Umair Hassan

All Publications

• 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