Biology subjects

Hassan, U.

Publications and source records attributed to Hassan, U..

5 recordsLinked to original sources

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.

neuroscience↗

bioRxiv2024

Sensory Entrained TMS (seTMS) enhances motor cortex excitability

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.

neuroscience↗

bioRxiv2024

Pulsed inhibition of corticospinal excitability by the thalamocortical sleep spindle

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 sleep-dependent 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 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 and measured motor evoked potentials (MEP) to characterize corticospinal excitability during sleep spindles. We found a net suppression of MEP amplitudes during spindles, driven by selective inhibition during the falling flank of the spindle oscillation, but no inhibition during its peak, rising flank, and trough. Importantly, this phasic inhibition occurred on top of the general sleep-related inhibition observed during spindle-free NREM sleep and did not extend into the immediate refractory post-spindle periods. We conclude that spindles exert asymmetric "pulsed inhibition" of corticospinal excitability, which is assumedly relevant for processes of phase-dependent plasticity. These findings and the developed real-time spindle targeting methods will enable future studies to uncover the causal role of spindles in synaptic plasticity and systems memory consolidation.

neuroscience↗

bioRxiv2023

Auditory confounds can drive online effects of transcranial ultrasonic stimulation in humans

Transcranial ultrasonic stimulation (TUS) is rapidly emerging as a promising non-invasive neuromodulation technique. TUS is already well-established in animal models, providing foundations to now optimize neuromodulatory efficacy for human applications. Across multiple studies, one promising protocol, pulsed at 1000 Hz, has consistently resulted in motor cortical inhibition in humans (Fomenko et al., 2020). At the same time, a parallel research line has highlighted the potentially confounding influence of peripheral auditory stimulation arising from TUS pulsing at audible frequencies. In this study, we disentangle direct neuromodulatory and indirect auditory contributions to motor inhibitory effects of TUS. To this end, we include tightly matched control conditions across four experiments, one preregistered, conducted independently at three institutions. We employed a combined transcranial ultrasonic and magnetic stimulation paradigm, where TMS-elicited motor-evoked potentials (MEPs) served as an index of corticospinal excitability. First, we replicated motor inhibitory effects of TUS but showed through both tight controls and manipulation of stimulation intensity, duration, and auditory masking conditions that this inhibition was driven by peripheral auditory stimulation, not direct neuromodulation. Further, we consider neuromodulation beyond driving overall excitation/inhibition and show preliminary evidence of how TUS might interact with ongoing neural dynamics instead. Primarily, this study highlights the substantial shortcomings in accounting for the auditory confound in prior TUS-TMS work where only a flip-over sham and no active control was used. The field must critically reevaluate previous findings given the demonstrated impact of peripheral confounds. Further, rigorous experimental design via (in)active control conditions is required to make substantiated claims in future TUS studies. Only when direct effects are disentangled from those driven by peripheral confounds can TUS fully realize its potential for research and clinical applications.

neuroscience↗

bioRxiv2022

Automated real-time EEG sleep spindle detection for brain state-dependent brain stimulation

Sleep spindles are a hallmark electroencephalographic (EEG) feature of non-rapid eye movement (NREM) sleep and believed to be instrumental for sleep-dependent memory reactivation and consolidation. However, direct proof of their causal relevance is hard to obtain, and our understanding of their immediate neurophysiological consequences is limited. To investigate their causal role, spindles need to be targeted in real-time with sensory or non-invasive brain stimulation techniques. While fully automated offline detection algorithms are well established, spindle detection in real time is highly challenging due to their spontaneous and transient nature. Here, we present the real-time spindle detector (RTSD), a robust multi-channel EEG signal processing algorithm that enables the automated triggering of stimulation during sleep spindles in a phase-specific manner. We validated the RTSD method by streaming pre-recorded sleep EEG datasets to a real-time computer system running a Simulink(R) Real-Time implementation of the algorithm. Sleep spindles were detected with high levels of sensitivity ([~]83%) and precision ([~]78%) and an F1-score of [~]0.81 in reference to state-of-the-art offline algorithms (which reached similar levels when compared to each other), for both naps and full nights, and largely independent of sleep scoring information. Detected spindles were comparable in frequency, duration, amplitude, and symmetry, and showed the typical time-frequency characteristics as well as a centroparietal topography. Spindles were detected close to their center and reliably at the predefined target phase. The RTSD algorithm therefore empowers researchers to target spindles during human sleep and apply the stimulation method and experimental paradigm of their choice.

neuroscience↗