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Darmani, G.

Publications and source records attributed to Darmani, G..

3 recordsLinked to original sources

Deep Brain Ultrasound Augments Human Attention

BackgroundDeep brain ultrasound offers a novel means of modulating human cognition by noninvasively targeting subcortical structures that were previously accessible only through invasive procedures. While decades of research have mapped cortical circuits of attention, the causal roles of deep hubs such as the basal ganglia and thalamus remain poorly understood in the healthy human brain. Objectives/HypothesisTo test whether low intensity transcranial ultrasound stimulation (TUS) of two nodes in the basal ganglia-thalamic network, the globus pallidus internus (GPi) and the pulvinar, causally alters visual attention. We hypothesized that TUS-induced modulations in attentional performance would be site specific, reflecting distinct circuit functions. ResultsAcross sessions, focal TUS accelerated reaction time in a visual search task, indicating augmented attention. Reaction time improvements were observed after stimulation relative to baseline. A dissociation emerged across sites: both GPi and pulvinar enhanced reaction times, but pulvinar yielded more robust benefits for target present trials at peripheral eccentricities, and improved search efficiency in the same trials. ConclusionsThese findings provide causal evidence that human attentional control can be steered at deep subcortical sites. TUS offers a practical approach for dissecting circuit level contributions to cognition and a potential noninvasive avenue for enhancing attention and other cognitive or affective functions.

neuroscience↗

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↗

TMS-evoked EEG potentials from prefrontal and parietal cortex: reliability, site specificity, and effects of dextromethorphan

Measuring the brains response to transcranial magnetic stimulation (TMS) with electroencephalography (EEG) offers a unique insight into the local cortical circuits and networks activated following stimulation, particularly in non-motor regions where less is known about TMS physiology. However, the mechanisms underlying TMS-evoked EEG potentials (TEPs) remain largely unknown. We assessed TEP reliability, site-specificity, and sensitivity to changes in excitatory neurotransmission mediated by n-methyl-d-aspartate (NMDA) receptors following stimulation of non-motor regions. In fourteen male volunteers, resting EEG and TEPs from prefrontal (PFC) and parietal (PAR) cortex were measured before and after administration of either dextromethorphan (an NMDA receptor antagonist) or placebo across two sessions separated by at least a week in a double-blinded pseudo-randomised crossover design. At baseline, TEPs showed lower within-than between-subject variability for both stimulation sites across sessions, demonstrating the reliability of non-motor TEPs within individuals. There were differences in amplitude between PFC and PAR TEPs across a wide time range (15-250 ms), however the signals were correlated after ~80 ms, suggesting that early peaks reflect site-specific activity, whereas late peaks reflect activity patterns less dependent on the stimulated sites. TEPs were not altered following dextromethorphan compared to placebo, however low frequency resting oscillations were reduced in power. Our findings suggest that TEPs from PFC and PAR: 1) are reliable within and variable between individuals; 2) reflect stimulation site specific activity across early time periods (<80 ms); and 3) are not sensitive to changes in NMDA receptor-mediated neurotransmission.

neuroscience↗