Focused ultrasound to bilateral thalamic nuclei significantly improves human cognitive attention in a frequency- and intensity-dependent manner

BACKGROUND: The centromedian nucleus of the thalamus (CMT) is a core arousal center with potential for enhancing attention and alertness. While emergent low intensity focused ultrasound (LIFU) can reach this area, the stimulation paradigms which may enhance function in humans remain unknown. METHODS: In a within-subject, double-blind, sham-controlled paradigm, we administered bilateral stimulation of the CMT in N = 16 healthy adult participants using a novel wearable focused ultrasound neuromodulation device and 3 distinct pulse frequencies (1Hz, 5Hz, and 25Hz) and a diffuse unfocused sham stimulation (4 LIFU sessions per person; 64 total sessions). We tested neuroradiological MRI scan reads for safety, and single session effects of LIFU on alertness using a visual Oddball task and recorded electroencephalography (EEG) during the task. RESULTS: We found that a brief period of 50 s 25Hz LIFU stimulation (20% duty cycle) significantly enhanced reaction time in comparison to sham on a directed attention Oddball task for at least 40 min post-stimulation (linear mixed effects model; post-hoc p < 0.05). Pre-post task electrocortical EEG revealed a significant correlation between reaction time and the prevalence of arousal related alpha and theta cortical activity (p < 0.05). Examination of ISPPA dose dependence revealed bidirectional modulation of arousal state, with lower acoustic pressure intensities preferentially enhancing cognitive function (p < 0.01). Pre- and post-MRI scans showed no structural neuroradiological changes due to stimulation. CONCLUSIONS: Collectively, these findings demonstrate that targeted LIFU stimulation of the CMT can safely enhance attention and alertness in healthy individuals with carefully designed parameters.