Long term study of motivational and cognitive effects of low-intensity focused ultrasound neuromodulation in the dorsal striatum of nonhuman primates

Abstract

Noninvasive brain stimulation using transcranial focused ultrasound (FUS) has many potential applications as a research and clinical tool, including incorporation into neural prosthetics for cognitive rehabilitation. To develop this technology, it is necessary to evaluate the safety and efficacy of FUS neuromodulation for specific brain targets and cognitive functions. It is also important to test whether repeated long-term application of FUS to deep brain targets improves or degrades behavioral and cognitive function. To this end, we investigated the effects of FUS in the dorsal striatum of nonhuman primates (NHP) performing a visual-motor decision-making task for small or large rewards. Over the course of 2 years, we performed 129 and 147 FUS applications, respectively, in two NHP. FUS (0.5 MHz @ 0.2-0.8 MPa) was applied to the putamen and caudate in both hemispheres to evaluate the effects on movement accuracy, motivation, decision accuracy, and response time. Sonicating the caudate or the putamen unilaterally resulted in modest but statistically significant improvements in motivation and decision accuracy, but at the cost of slower reaction times. The effects were dose (i.e., FUS pressure) and reward dependent. There was no effect on reaching accuracy, nor was there long-term behavioral impairment or neurological trauma evident on T1-weighted, T2-weighted, or susceptibility-weighted MRI scans. Sonication also resulted in significant changes in resting state functional connectivity between the caudate and multiple cortical regions. The results indicate that applying FUS to the dorsal striatum can positively impact the motivational and cognitive aspects of decision making. The capability of FUS to improve motivation and cognition in NHPs points to its therapeutic potential in treating a wide variety of human neural diseases, and warrants further development as a novel technique for non-invasive deep brain stimulation.

Abstract via europepmc.

Flags from extraction

• exposures[0].timing.pulse_repetition_frequency_hz — PRF converted from the paper's phrase 'twice per second' (unit conversion, not computed from other stated numbers).
• exposures[1].timing.pulse_repetition_frequency_hz — PRF converted from the paper's phrase 'twice per second' (unit conversion, not computed from other stated numbers).
• exposures[0].in_situ.pressure_kpa — Domain assigned in_situ because the paper states 'The acoustic pressures reported in the Results refer to the derated values' (measured through ex vivo NHP skull); the quoted sentence with the four kPa values itself only describes free-field+skull calibration, not the derating explicitly.
• exposures[1].in_situ.pressure_kpa — Same as exposures[0]: domain assigned in_situ per the paper's separate statement that reported pressures are derated values.
• n_subjects — Paper never states a single total exposed to ultrasound; value combines the 2 NHP with repeated behavioural FUS (P, Q) and the 1 additional NHP (O) that received FUS only before fMRI, per 'Three (O, P, Q) underwent one session each of anesthetized fMRI preceded by FUS sonication.'
• n_sessions_per_subject — Session counts differ drastically by subject and purpose (P: 129 real + 40 sham; Q: 147 real + 41 sham; O: 1 fMRI session); no single value applies.
• auditory_control — Study addressed auditory confounds via an offline (temporally separated) protocol and audio recordings showing no difference between real and sham sonication, rather than one of the standard control categories.
• sham_type — Sham used the same equipment powered on but with 'FUS pressure set to zero' rather than a fully powered-off/blocked transducer; closest available category is inactive_transducer.