Abstract: Transcranial focused ultrasound stimulation (TUS) is becoming important in cognitive and affective neuroscience because it can deliver acoustic energy to cortical and subcortical targets with high spatial precision. For psychological research, TUS makes it possible to ask causal questions at two temporal scales: how a target region contributes to an ongoing psychological process at a particular moment, and how stimulation-induced changes in neural state influence subsequent behavior. We therefore organize this review around the distinction between online and offline TUS, and treat these two modes as complementary routes for causal investigation in psychology.
In human research, stimulation parameters are usually described through several dimensions, including acoustic output, temporal structure, and exposure descriptors. Acoustic output includes carrier frequency and pressure-related measures; temporal structure includes pulse duration, pulse repetition frequency, duty cycle, and total sonication duration; and exposure descriptors include spatial-peak pulse-average intensity, spatial-peak temporal-average intensity, and mechanical index. This organization is useful because no single parameter can be equated with excitation or inhibition. The similar protocol may yield different outcomes when target depth, skull transmission, focal coverage, baseline neural state, task context, and outcome measure differ.
Online TUS is delivered during or immediately around a task event or neural response. Its defining feature is temporal locking: ultrasound pulses can be aligned with sensory input, response preparation, decision competition, or the onset of inhibitory control. This makes online TUS suitable for testing when a region is causally involved in perception, action, or control. Somatosensory studies show that stimulation of primary somatosensory cortex can reduce early evoked potentials while improving tactile discrimination, suggesting that TUS may reshape sensory coding rather than simply enhance or suppress cortical activity. Thalamic studies further extend causal manipulation to deep sensory relay structures. In visual research, stimulation of primary visual cortex and frontal eye fields has been used to modulate visually evoked activity and bias spatial choice under uncertainty. In the motor system, online TUS has been used to examine motor cortex excitability, intracortical facilitation and inhibition, and movement-related cortical potentials. Work on response inhibition shows that right inferior frontal gyrus stimulation improves stopping only when the pulse is time-locked to the stop signal, indicating an effect on inhibitory timing rather than a general benefit. Pain studies targeting the insula and dorsal anterior cingulate cortex further show how online TUS can dissociate immediate regional roles in sensory intensity, salience evaluation, and autonomic regulation.
Offline TUS separates stimulation from the main behavioral or physiological measurement. It focuses on aftereffects that persist for minutes or longer after sonication has ended, and is therefore suited to questions about sustained changes in excitability, excitation-inhibition balance, neurochemical state, functional connectivity, and plasticity-like processes. In emotional research, offline stimulation of prefrontal and limbic regions has been associated with changes in helplessness, approach-avoidance behavior, mood, amygdala reactivity, and symptoms of anxiety or depression. These findings suggest that TUS can test not only cortical regulatory mechanisms, but also deep affective circuits that are difficult to access with transcranial magnetic or electrical stimulation. In response inhibition, offline TUS of basal ganglia and insular-prefrontal pathways provides causal evidence that stopping depends on a distributed hierarchy rather than a single prefrontal node. In memory and reward research, stimulation of the ventromedial anterior temporal lobe or nucleus accumbens has been linked to changes in semantic memory, reward sensitivity, feedback learning, and reward-network connectivity. Offline pain and motor studies further show that TUS can alter pain thresholds, temporal summation, chronic pain ratings, corticospinal excitability, interhemispheric balance, and motor symptoms, although these effects depend on target, baseline state, medication status, and acoustic dose.
Rigorous interpretation of TUS findings also requires stronger control of confounds and more transparent safety reporting. Online studies are especially vulnerable to auditory and somatosensory confounds because the acoustic pulse is synchronized with the task event. Sham stimulation, masking noise, active control sites, acoustic blocking, and vibration-matched controls should be selected according to the inference being tested. For safety, future studies should report nominal device settings, the basis of intensity estimation, in situ pressure and intensity when available, mechanical index or transcranial mechanical index, thermal estimates, stimulation duration, and skull-transmission assumptions. Recent adverse-event reports further indicate that conservative safety margins and individualized acoustic simulation are essential, especially for low-frequency, long-pulse, or higher-pressure protocols.
In sum, online and offline TUS answer different causal questions. Online TUS is most useful for identifying the timing of causal involvement in ongoing processing; offline TUS is most useful for testing how stimulation-induced brain-state changes alter later cognition, emotion, behavior, or symptoms. By distinguishing these modes, we aim to move TUS research in psychology from proof-of-principle demonstrations toward reproducible, mechanism-focused causal studies.

Key words: transcranial focused ultrasound stimulation, online stimulation, offline stimulation, deep brain stimulation, neuromodulation