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Low-intensity transcranial ultrasound stimulation (TUS) is an emerging non-invasive technique for focally modulating human brain function. The mechanisms and neurochemical substrates underlying TUS neuromodulation in humans and how these relate to excitation and inhibition are still poorly understood. In 24 healthy controls, we separately stimulated two deep cortical regions and investigated the effects of theta-burst TUS, a protocol shown to increase corticospinal excitability, on the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) and functional connectivity. We show that theta-burst TUS in humans selectively reduces GABA levels in the posterior cingulate, but not the dorsal anterior cingulate cortex. Functional connectivity increased following TUS in both regions. Our findings suggest that TUS changes overall excitability by reducing GABAergic inhibition and that changes in TUS-mediated neuroplasticity last at least 50 mins after stimulation. The difference in TUS effects on the posterior and anterior cingulate could suggest state- or location-dependency of the TUS effect—both mechanisms increasingly recognized to influence the brain’s response to neuromodulation. The neural mechanisms underlying transcranial ultrasound stimulation (TUS) in humans are not well understood. Here, the authors show that theta-burst stimulation reduces gamma-aminobutyric acid (GABA) levels in the posterior cingulate cortex, as well as increasing functional connectivity in the anterior and posterior cingulate cortex.

The neural mechanisms mediating sensory-guided decision-making have received considerable attention, but animals often pursue behaviors for which there is currently no sensory evidence. Such behaviors are guided by internal representations of choice values that have to be maintained even when these choices are unavailable. We investigated how four macaque monkeys maintained representations of the value of counterfactual choices—choices that could not be taken at the current moment but which could be taken in the future. Using functional magnetic resonance imaging, we found two different patterns of activity co-varying with values of counterfactual choices in a circuit spanning the hippocampus, the anterior lateral prefrontal cortex and the anterior cingulate cortex. Anterior cingulate cortex activity also reflected whether the internal value representations would be translated into actual behavioral change. To establish the causal importance of the anterior cingulate cortex for this translation process, we used a novel technique, transcranial focused ultrasound stimulation, to reversibly disrupt anterior cingulate cortex activity.Fouragnan et al. used neuroimaging and ultrasound neuromodution in non-human primates to demonstrate the causal role of the anterior cingulate cortex in translating counterfactual values in future choices.

Current computational accounts posit that, in simple binary choices, humans accumulate evidence in favour of the different alternatives before committing to a decision. Neural correlates of this accumulating activity have been found during perceptual decisions in parietal and prefrontal cortex; however the source of such activity in value-based choices remains unknown. Here we use simultaneous EEG–fMRI and computational modelling to identify EEG signals reflecting an accumulation process and demonstrate that the within- and across-trial variability in these signals explains fMRI responses in posterior-medial frontal cortex. Consistent with its role in integrating the evidence prior to reaching a decision, this region also exhibits task-dependent coupling with the ventromedial prefrontal cortex and the striatum, brain areas known to encode the subjective value of the decision alternatives. These results further endorse the proposition of an evidence accumulation process during value-based decisions in humans and implicate the posterior-medial frontal cortex in this process. Parietal and prefrontal cortices gather information to make perceptual decisions, but it is not known if the same is true for value-based choices. Here, authors use simultaneous EEG-fMRI and modelling to show that during value- and reward-based decisions this evidence is accumulated in the posterior medial frontal cortex.

Natural fluctuations in cardiac activity modulate brain activity associated with sensory stimuli, as well as perceptual decisions about low magnitude, near-threshold stimuli. However, little is known about the relationship between fluctuations in heart activity and other internal representations. Here we investigate whether the cardiac cycle relates to learning-related internal representations – absolute and signed prediction errors. We combined machine learning techniques with electroencephalography with both simple, direct indices of task performance and computational model-derived indices of learning. Our results demonstrate that just as people are more sensitive to low magnitude, near-threshold sensory stimuli in certain cardiac phases, so are they more sensitive to low magnitude absolute prediction errors in the same cycles. However, this occurs even when the low magnitude prediction errors are associated with clearly suprathreshold sensory events. In addition, participants exhibiting stronger differences in their prediction error representations between cardiac cycles exhibited higher learning rates and greater task accuracy. Previous work has shown that natural cardiac rhythms modulate the perception and reaction to sensory cues through changes in associated neural signals. Here, the authors show that sensitivity to prediction errors during reward learning is related to the phase of the cardiac cycle.

The orbitofrontal cortex (OFC) is a key brain region involved in complex cognitive functions such as reward processing and decision making. Neuroimaging studies have reported unilateral OFC response to reward-related variables; however, those studies rarely discussed this observation. Nevertheless, some lesion studies suggest that the left and right OFC contribute differently to cognitive processes. We hypothesized that the OFC asymmetrical response to reward could reflect underlying hemispherical difference in OFC functional connectivity. Using resting-state and reward-related functional MRI data from humans and from rhesus macaques, we first identified an asymmetrical response of the lateral OFC to reward in both species. Crucially, the subregion showing the highest reward-related asymmetry (RRA) overlapped with the region showing the highest functional connectivity asymmetry (FCA). Furthermore, the two types of asymmetries were found to be significantly correlated across individuals. In both species, the right lateral OFC was more connected to the default mode network compared to the left lateral OFC. Altogether, our results suggest a functional specialization of the left and right lateral OFC in primates.

People and other animals learn the values of choices by observing the contingencies between them and their outcomes. However, decisions are not guided by choice-linked reward associations alone; macaques also maintain a memory of the general, average reward rate – the global reward state – in an environment. Remarkably, global reward state affects the way that each choice outcome is valued and influences future decisions so that the impact of both choice success and failure is different in rich and poor environments. Successful choices are more likely to be repeated but this is especially the case in rich environments. Unsuccessful choices are more likely to be abandoned but this is especially likely in poor environments. Functional magnetic resonance imaging (fMRI) revealed two distinct patterns of activity, one in anterior insula and one in the dorsal raphe nucleus, that track global reward state as well as specific outcome events. Wittmann and colleagues show that not only single outcome events but also the global reward state (GRS) impact learning in macaques; low GRS drives explorative choices. Analyses of macaque BOLD signal reveals that GRS impacts activity in the anterior insula as well as the dorsal raphe nucleus.

Much work has investigated beneficial effects of mindfulness-based meditation methods, but less work has investigated potential risks and differences across meditation methods. We addressed this in a large pre-registered online survey including 613 mediators where we correlated participants’ experience with fifty meditation techniques to psychotic-like experiences (PLEs) and mystical experiences. We found a positive correlation for both PLEs and mystical experiences with techniques aiming at reducing phenomenological content (‘null-directed’, NDM) or classified as non-dual or less embodied. In contrast, methods aiming at achieving an enhanced cognitive state (CDM), also described as ‘attentional’ or strongly embodied, showed negative correlations with PLEs. Interestingly, participants’ subjectively perceived that all types of meditation techniques were preventative of PLEs but less so for NDM. Participants differed in their reasons for meditating, broadly grouped into associated with spiritual exploration and associated with health. Participants who meditated for spiritual reasons were more likely to choose NDM techniques and more likely to experience PLEs. In contrast, participants who meditated for health-related reasons were more likely to choose CDM techniques. This study provides important information for meditators about the relationship of different techniques with PLEs and the moderating influences of individual traits.

This Perspective article discusses the emerging potential of transcranial ultrasound stimulation (TUS) as a non-invasive neuromodulatory technique for enhancing self-regulatory processes, particularly emotion and sleep regulation, in healthy individuals. Offering high spatial precision and the ability to target both cortical and deep brain regions, TUS uses focused ultrasound waves to induce acute and delayed effects on brain activity. We propose that combining TUS with neurofeedback methods and/or specific cognitive training exercises may capitalise on these neuroplastic effects, thereby augmenting and prolonging their impact to support lasting improvements in self-regulation. We focus on the domains of sleep and emotion regulation, where such an integrated approach may strengthen resilience and promote healthier functioning in the general population. Our aim is to highlight the potential of TUS-based integrated interventions for supporting mental health and well-being in non-clinical populations and to outline key directions for future research.

Precisely neuromodulating deep brain regions could bring transformative advancements in both neuroscience and treatment. We demonstrate that non-invasive transcranial ultrasound stimulation (TUS) can selectively modulate deep brain activity and affect learning and decision making, comparable to deep brain stimulation (DBS). We tested whether TUS could causally influence neural and behavioural responses by targeting the nucleus accumbens (NAcc) using a reinforcement learning task. Twenty-six healthy adults completed a within-subject TUS–fMRI experiment with three conditions: TUS to the NAcc, dorsal anterior cingulate cortex (dACC), or Sham. After TUS, participants performed a probabilistic learning task during fMRI. TUS-NAcc altered BOLD responses to reward expectation in the NAcc and surrounding areas. It also affected reward-related behaviours, including win–stay strategy use, learning rate following rewards, learning curves, and repetition rates of rewarded choices. DBS-NAcc perturbed the same features, confirming target engagement. These findings establish TUS as a viable approach for non-invasive deep-brain neuromodulation. This study shows that non-invasive ultrasound to the human nucleus accumbens can modulate deep brain activity and enhance reward-guided learning, offering a potential alternative to invasive neuromodulation therapies.

Pavlovian biases reflect how evolutionarily hard-wired tendencies—automatic approach toward reward cues and withdrawal from threat cues—can interfere with flexible, goal-directed action. Such biases arise through three mechanisms: (a) anticipated rewards energize action while anticipated punishments suppress it (response bias), (b) agents learn differently from actions than from inactions (learning bias), and (c) reward/punishment cues themselves drive repetitive behavior, independent of outcomes (perseveration bias). The neural origin of these biases is unclear. Past evidence suggests dorsal anterior cingulate cortex (dACC) and anterior insula (aIns) as part of a “reset network” that rapidly responds to salient information and might contribute to these biases. We used transcranial ultrasonic stimulation (TUS) in 29 healthy participants to interfere with neural activity in these regions and test their causal role in a within-subject, counter-balanced design across three sessions (sham, TUS-dACC, TUS-aIns). Computational modeling revealed a functional differentiation of both regions in Pavlovian biases: while TUS to either region did not affect the response bias, TUS to the aIns decreased people’s learning bias, while TUS to dACC increased participants’ perseveration bias. Although the dACC and aIns are part of the same network and often co-activate during decision-making tasks, TUS interference reveals their distinct roles: the dACC mediates cue-dependent persistence while the aIns is critical for inferring whether outcomes are self-caused.