Non-invasive transcranial ultrasound stimulation for neuromodulation.

Transcranial ultrasound stimulation (TUS) holds great potential as a tool to alter neural circuits non-invasively in both animals and humans. In contrast to established non-invasive brain stimulation methods, ultrasonic waves can be focused on both cortical and deep brain targets with the unprecedented spatial resolution as small as a few cubic millimeters. This focusing allows exclusive targeting of small subcortical structures, previously accessible only by invasive deep brain stimulation devices. The neuromodulatory effects of TUS are likely derived from the kinetic interaction of the ultrasound waves with neuronal membranes and their constitutive mechanosensitive ion channels, to produce short term and long-lasting changes in neuronal excitability and spontaneous firing rate. After decades of mechanistic and safety investigation, the technique has finally come of age, and an increasing number of human TUS studies are expected. Given its excellent compatibility with non-invasive brain mapping techniques, such as electroencephalography (EEG) and functional magnetic resonance imaging (fMRI), as well as neuromodulatory techniques, such as transcranial magnetic stimulation (TMS), systemic TUS effects can readily be assessed in both basic and clinical research. In this review, we present the fundamentals of TUS for a broader audience. We provide up-to-date information on the physical and neurophysiological mechanisms of TUS, available readouts for its neural and behavioral effects, insights gained from animal models and human studies, potential clinical applications, and safety considerations. Moreover, we discuss the indirect effects of TUS on the nervous system through peripheral co-stimulation and how these confounding factors can be mitigated by proper control conditions.

Paired-pulse transcranial magnetic stimulation of primary somatosensory cortex differentially modulates perception and sensorimotor transformations.

Intermodal selective attention is generally associated with facilitation of relevant information. However, recent studies demonstrate reduced activation of primary somatosensory cortex (S1) with continuous vibrotactile tracking during bimodal stimulation. Reduced activation has been hypothesized to reflect an interaction between the sensorimotor and intermodal requirements of the tracking task. Recently, it has been shown that transcranial magnetic stimulation (TMS) involving a supra-threshold test stimulus (TS) preceded by a sub-threshold conditioning stimulus (CS) adversely affects tactile perception by altering excitability of local intracortical circuits. The purpose of the current paper was to use TMS to assess the effects of differential sensorimotor requirements in the right sensorimotor cortex upon local intracortical networks and sensory processing in the left primary somatosensory cortex during constant multimodal stimulation. Single and paired-pulse TMS was used to probe intracortical networks in S1 and sensory processing during a sensorimotor task where a vibrotactile stimulus to the right index finder guided either continuous or discrete sensorimotor responses of the left hand. It was hypothesized that paired-pulse TMS would alter local intracortical networks and reduce performance during the discrete sensorimotor task, but that these effects would be mitigated during the continuous sensorimotor task, possibly a reflection of reduced S1 activation observed previously during a similar continuous sensorimotor task. Regardless of sensorimotor requirements, single-pulse TMS delivered over S1 decreased sensorimotor performance. Paired-pulse TMS further decreased sensorimotor performance only when the vibrotactile stimulus guided a discrete motor response but not when it was required to continuously guide the motor response. This effect disappeared when the TS was replaced by a sub-threshold stimulus. These results suggest that the CS facilitates sensory output neurons during perceptual detection but that differential responsiveness of local cortical networks in S1 suppresses the CS effects during continuous sensory-guided movement. This study highlights the importance of sensorimotor requirements in determining the net result of task-related sensory processing in S1.