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Background: The nucleus accumbens (NAc) is a key node of the brain reward circuit driving reward-related behavior. Dysregulation of NAc has been demonstrated to contribute to pathological markers of addiction in substance use disorder (SUD) making it a potential therapeutic target for brain stimulation. Transcranial focused ultrasound (tFUS) is an emerging non-invasive brain stimulation approach that can modulate deep brain regions with a high spatial resolution. However, there is currently no evidence showing how the brain activity of NAc and brain functional connectivity within the reward network neuromodulated by tFUS on the NAc. Methods: In this pilot study, we carried out a single-blind, sham-controlled clinical trial using functional magnetic resonance imaging (fMRI) to investigate the underlying mechanism of tFUS neuromodulating the reward network through NAc in ten healthy adults. Specifically, the experiment consists of a 20- min concurrent tFUS/fMRI scan and two 24-min resting-state fMRI before and after the tFUS session. Results: Firstly, our results demonstrated the feasibility and safety of 20-min tFUS on NAc. Additionally, our findings demonstrated that bilateral NAc was inhibited during tFUS on the left NAc compared to sham. Lastly, increased functional connectivity between the NAc and medial prefrontal cortex (mPFC) was observed after tFUS on the left NAc, but no changes for the sham group. Conclusion: Delivering tFUS to the NAc can modulate brain activations and functional connectivity within the reward network. These preliminary findings suggest that tFUS could be potentially a promising neuromodulation tool for the direct and non-invasive management of the NAc and shed new light on the treatment for SUD and other brain diseases that involve reward processing. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a degenerative joint disease, the prevalence of OA is increasing, and the elderly are the most common in patients with OA. OA has a severe impact on the daily life of patients, this increases the demand for treatment of OA. In recent years, the application of non-invasive brain stimulation (NIBS) has attracted extensive attention. It has been confirmed that NIBS plays an important role in regulating cortical excitability and oscillatory rhythm in specific brain regions. In this review, we summarized the therapeutic effects and mechanisms of different NIBS techniques in OA, clarified the potential of NIBS as a treatment choice for OA, and provided prospects for further research in the future. [ABSTRACT FROM AUTHOR]

Background: Transcranial focused ultrasound (tFUS) is a noninvasive brain stimulation method that may modulate deep brain structures. This study investigates whether sonication of the right anterior thalamus would modulate thermal pain thresholds in healthy individuals. Methods: We enrolled 19 healthy individuals in this three-visit, double-blind, sham-controlled, crossover trial. Participants first underwent a structural MRI scan used solely for tFUS targeting. They then attended two identical experimental tFUS visits (counterbalanced by condition) at least one week apart. Within the MRI scanner, participants received two, 10-min sessions of either active or sham tFUS spread 10 min apart targeting the right anterior thalamus [fundamental frequency: 650 kHz, Pulse repetition frequency: 10 Hz, Pulse Width: 5 ms, Duty Cycle: 5%, Sonication Duration: 30s, Inter-Sonication Interval: 30 s, Number of Sonications: 10, ISPTA.0 995 mW/cm2, ISPTA.3 719 mW/cm2, Peak rarefactional pressure 0.72 MPa]. The primary outcome measure was quantitative sensory thresholding (QST), measuring sensory, pain, and tolerance thresholds to a thermal stimulus applied to the left forearm before and after right anterior thalamic tFUS. Results: The right anterior thalamus was accurately sonicated in 17 of the 19 subjects. Thermal pain sensitivity was significantly attenuated after active tFUS. The pre-post x active-sham interaction was significant (F(1,245.95) = 4.03, p = .046). This interaction indicates that in the sham stimulation condition, thermal pain thresholds decreased 1.08 °C (SE = 0.28) pre-post session, but only decreased .51 °C (SE = 0.30) pre-post session in the active stimulation group. Conclusions: Two 10-min sessions of anterior thalamic tFUS induces antinociceptive effects in healthy individuals. Future studies should optimize the parameter space, dose and duration of this effect which may lead to multi-session tFUS interventions for pain disorders.

Background: The nucleus accumbens (NAc) is a key node of the brain reward circuit driving reward-related behavior. Dysregulation of NAc has been demonstrated to contribute to pathological markers of addiction in substance use disorder (SUD) making it a potential therapeutic target for brain stimulation. Transcranial focused ultrasound (tFUS) is an emerging non-invasive brain stimulation approach that can modulate deep brain regions with a high spatial resolution. However, there is currently no evidence showing how the brain activity of NAc and brain functional connectivity within the reward network neuromodulated by tFUS on the NAc., Methods: In this pilot study, we carried out a single-blind, sham-controlled clinical trial using functional magnetic resonance imaging (fMRI) to investigate the underlying mechanism of tFUS neuromodulating the reward network through NAc in ten healthy adults. Specifically, the experiment consists of a 20-min concurrent tFUS/fMRI scan and two 24-min resting-state fMRI before and after the tFUS session., Results: Firstly, our results demonstrated the feasibility and safety of 20-min tFUS on NAc. Additionally, our findings demonstrated that bilateral NAc was inhibited during tFUS on the left NAc compared to sham. Lastly, increased functional connectivity between the NAc and medial prefrontal cortex (mPFC) was observed after tFUS on the left NAc, but no changes for the sham group., Conclusion: Delivering tFUS to the NAc can modulate brain activations and functional connectivity within the reward network. These preliminary findings suggest that tFUS could be potentially a promising neuromodulation tool for the direct and non-invasive management of the NAc and shed new light on the treatment for SUD and other brain diseases that involve reward processing., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Peng, Connolly, Sutton, Robinson, Baker-Vogel, Short and Badran.)

Transcranial focused ultrasound (tFUS) is a noninvasive brain stimulation method that may modulate deep brain structures. This study investigates whether sonication of the right anterior thalamus would modulate thermal pain thresholds in healthy individuals. We enrolled 19 healthy individuals in this three-visit, double-blind, sham-controlled, crossover trial. Participants first underwent a structural MRI scan used solely for tFUS targeting. They then attended two identical experimental tFUS visits (counterbalanced by condition) at least one week apart. Within the MRI scanner, participants received two, 10-min sessions of either active or sham tFUS spread 10 min apart targeting the right anterior thalamus [fundamental frequency: 650 kHz, Pulse repetition frequency: 10 Hz, Pulse Width: 5 ms, Duty Cycle: 5%, Sonication Duration: 30s, Inter-Sonication Interval: 30 s, Number of Sonications: 10, ISPTA. 0 995 mW/cm2, ISPTA. 3 719 mW/cm2, Peak rarefactional pressure 0.72 MPa]. The primary outcome measure was quantitative sensory thresholding (QST), measuring sensory, pain, and tolerance thresholds to a thermal stimulus applied to the left forearm before and after right anterior thalamic tFUS. The right anterior thalamus was accurately sonicated in 17 of the 19 subjects. Thermal pain sensitivity was significantly attenuated after active tFUS. The pre-post x active-sham interaction was significant (F(1,245.95) = 4.03, p =.046). This interaction indicates that in the sham stimulation condition, thermal pain thresholds decreased 1.08 °C (SE = 0.28) pre-post session, but only decreased.51 °C (SE = 0.30) pre-post session in the active stimulation group. Two 10-min sessions of anterior thalamic tFUS induces antinociceptive effects in healthy individuals. Future studies should optimize the parameter space, dose and duration of this effect which may lead to multi-session tFUS interventions for pain disorders. • Transcranial focused ultrasound (FUS) is a new form of neuromodulation. • Low Intensity Focused Ultrasound Pulsation (LIFUP) modulates deep brain structures. • We administered LIFUP within the MRI scanner to modulate pain in healthy adults. • In a double-blind design, our findings reveal LIFUP is anti-nociceptive. • Computational analysis of ultrasound beam projection reveals high target engagement. [ABSTRACT FROM AUTHOR]

Low-intensity transcranial focused ultrasound stimulation (TFUS) holds great promise as a highly focal technique for transcranial stimulation even for deep brain areas. Yet, knowledge about the safety of this novel technique is still limited. To systematically review safety related aspects of TFUS. The review covers the mechanisms-of-action by which TFUS may cause adverse effects and the available data on the possible occurrence of such effects in animal and human studies. Initial screening used key term searches in PubMed and bioRxiv, and a review of the literature lists of relevant papers. We included only studies where safety assessment was performed, and this results in 33 studies, both in humans and animals. Adverse effects of TFUS were very rare. At high stimulation intensity and/or rate, TFUS may cause haemorrhage, cell death or damage, and unintentional blood-brain barrier (BBB) opening. TFUS may also unintentionally affect long-term neural activity and behaviour. A variety of methods was used mainly in rodents to evaluate these adverse effects, including tissue staining, magnetic resonance imaging, temperature measurements and monitoring of neural activity and behaviour. In 30 studies, adverse effects were absent, even though at least one Food and Drug Administration (FDA) safety index was frequently exceeded. Two studies reported microhaemorrhages after long or relatively intense stimulation above safety limits. Another study reported BBB opening and neuronal damage in a control condition, which intentionally and substantially exceeded the safety limits. Most studies point towards a favourable safety profile of TFUS. Further investigations are warranted to establish a solid safety framework for the therapeutic window of TFUS to reliably avoid adverse effects while ensuring neural effectiveness. The comparability across studies should be improved by a more standardized reporting of TFUS parameters. • TFUS is an emerging non-invasive stimulation method with excellent focality • We summarize the safety-related data from the available literature. • Adverse effects were absent in 30 studies, and were reported in 3 studies. • Many studies used parameters outside safety limits for diagnostic ultrasound. • Further studies are warranted to establish the safety margin for TFUS. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a degenerative joint disease, the prevalence of OA is increasing, and the elderly are the most common in patients with OA. OA has a severe impact on the daily life of patients, this increases the demand for treatment of OA. In recent years, the application of non-invasive brain stimulation (NIBS) has attracted extensive attention. It has been confirmed that NIBS plays an important role in regulating cortical excitability and oscillatory rhythm in specific brain regions. In this review, we summarized the therapeutic effects and mechanisms of different NIBS techniques in OA, clarified the potential of NIBS as a treatment choice for OA, and provided prospects for further research in the future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhu, Luo, Wang and Zhang.)

Objective. Transcranial focused ultrasound (tFUS) is a neuromodulation technique which has been the focus of increasing interest for noninvasive brain stimulation with high spatial specificity. Its ability to excite and inhibit neural circuits as well as to modulate perception and behavior has been demonstrated, however, we currently lack understanding of how tFUS modulates the ways neurons interact with each other. This understanding would help elucidate tFUS's mechanism of systemic neuromodulation and allow future development of therapies for treating neurological disorders. Approach. In this study, we investigate how tFUS modulates neural interaction and response to peripheral electrical limb stimulation through intracranial multi-electrode recordings in the rat somatosensory cortex. We deliver ultrasound in a pulsed pattern to induce frequency dependent plasticity in a manner similar to what is found following electrical stimulation. Main Results. We show that neural firing in response to peripheral electrical stimulation is increased after ultrasound stimulation at all frequencies, showing tFUS induced changes in excitability of individual neurons in vivo . We demonstrate tFUS sonication repetition frequency dependent pairwise correlation changes between neurons, with both increases and decreases observed at different frequencies. Significance. These results extend previous research showing tFUS to be capable of inducing synaptic depression and demonstrate its ability to modulate network dynamics as a whole., (© 2022 IOP Publishing Ltd.)

Sleep is a universal and evolutionarily conserved behavior among many animal species, yet we do not have a fundamental understanding of why animals need to sleep. What we do know, however, is that sleep is critical for behavioral performance during the waking period and for long-term brain health. Here we provide an overview of some putative mechanisms that mediate the restorative effects of sleep, namely metabolic biosynthesis, fluid perfusion, and synaptic homeostasis. We then review recent experimental findings that advance the possibility of inducing sleep-like slow-wave activity (SWA) during wakefulness or enhance SWA during sleep in a top-down manner using noninvasive brain stimulation. SWA induction and SWA enhancement are believed to recapitulate the beneficial effects of sleep independent of the actual state of the subjects. If confirmed, these observations will change the way in which we investigate the neural correlates of sleep, thus paving the way for comprehending and actively controlling its restorative function., (© 2022 Wiley Periodicals LLC.)

For last decade, low-intensity transcranial focused ultrasound (tFUS) has been rapidly developed for a myriad of successful applications in neuromodulation. tFUS possesses high spatial resolution, focality and depth penetration as a noninvasive neuromodulation tool. Despite the promise, confounding activation can be observed in rodents when stimulation parameters are not selected carefully. Here we summarize the existing classes of observations for ultrasound neuromodulation: ultrasound directly activates a localized area, or ultrasound indirectly activates auditory pathways, which further propagates to other cortical networks. We also present control in vivo animal studies, which suggest that underlying tFUS brain modulation is characterized by localized activation independent of auditory networks activations., Competing Interests: Conflict of interest The authors declare no conflict of interest.