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High-resolution rodent functional magnetic resonance imaging (fMRI) enables vessel-specific hemodynamic mapping, capturing changes in cerebral blood volume, flow, and oxygenation at the level of individual penetrating arterioles and venules. This 'single-vessel' fMRI approach bridges findings from imaging methods with higher spatiotemporal resolution, offering a translational platform to better interpret the vascular origin of fMRI signals observed in human brains. Combining fMRI with neurotechniques, such as optogenetics or chemogenetics, along with simultaneous electrophysiological recordings or fiber photometry, enables cross-scale brain dynamic mapping of brain activity and neurovascular coupling. Multimodal rodent fMRI enables the dissection of contributions from local excitatory and inhibitory neural networks, neuro-glio-vascular interactions, and neuromodulatory systems, to fMRI signals across different brain areas. Despite extensive functional mapping studies using rodent functional magnetic resonance imaging (fMRI), interpreting the fMRI signals in relation to their neuronal origins remains challenging due to the hemodynamic nature of the response. Ultra high-resolution rodent fMRI, beyond merely enhancing spatial specificity, has revealed vessel-specific hemodynamic responses, highlighting the distinct contributions of intracortical arterioles and venules to fMRI signals. This 'single-vessel' fMRI approach shifts the paradigm of rodent fMRI, enabling its integration with other neuroimaging modalities to investigate neuro-glio-vascular (NGV) signaling underlying a variety of brain dynamics. Here, we review the emerging trend of combining multimodal fMRI with opto/chemogenetic neuromodulation and genetically encoded biosensors for cellular and circuit-specific recording, offering unprecedented opportunities for cross-scale brain dynamic mapping in rodent models. [ABSTRACT FROM AUTHOR]

Human sensory, cognitive, and physiological systems are constantly challenged by changes in the environment, goals, and expectations, and natural regulatory mechanisms that are a part of the body's effort to anticipate and respond to physiological demands caused by a variety of factors, including physical activity. Evidence from awake and behaving nonhuman species has clearly shown how physiological states can impact systems associated with arousal and attention, but there is no similar understanding of the interplay between states and attentional processes in humans. We bridge this gap using convergent evidence from studies of humans engaged in physical activity and simultaneous noninvasive neural recordings, and we propose that there are two physically activated modes of attentional control: altered gain control and differential neuromodulation of cortical control networks. As we navigate through the day, our attentional control processes are constantly challenged by changing sensory information, goals, expectations, and motivations. At the same time, our bodies and brains are impacted by changes in global physiological state that can influence attentional processes. Based on converging lines of evidence from brain recordings in physically active humans and nonhumans, we propose a new framework incorporating at least two physically activated modes of attentional control in humans: altered gain control and differential neuromodulation of control networks. We discuss the implications of this framework for understanding a broader range of states and cognitive functions studied both in the laboratory and in the wild. As we navigate through the day, our attentional control processes are constantly challenged by changing sensory information, goals, expectations, and motivations. At the same time, our bodies and brains are impacted by changes in global physiological state that can influence attentional processes. Based on converging lines of evidence from brain recordings in physically active humans and non‐humans, we propose a new framework incorporating at least two physically activated modes of attentional control in humans: altered gain control and differential neuromodulation of control networks. We discuss the implications of this framework for understanding a broader range of states and cognitive functions studied both in the laboratory and in the wild. [ABSTRACT FROM AUTHOR]

• Advances in applying optogenetics to spinal cord and peripheral nerves are reviewed. • Peripheral optogenetics allow precise modulation of nervous system beyond the brain. • Diverse applications of peripheral optogenetics across multiple systems are discussed. • Key challenges include operability, efficacy, and neuron-specific targeting. • Promising opportunities in neuromodulation and therapeutic strategy are highlighted. Peripheral optogenetics is an emerging neuromodulation technique that regulates the activity of the nervous system outside the brain through the expression of photosensitive proteins and the application of photic stimulation. This article reviews recent advances in applying optogenetics to the spinal cord and peripheral nerves, offering a comprehensive understanding of the functions and regulatory mechanisms of the peripheral nervous system through the modulation of specific neuronal activities. By showcasing novel opportunities for disease treatment, this technique opens new avenues in psychophysiological research and neural regulation therapy. Despite current challenges, such as operability, effectiveness, and selective neuron targeting, peripheral optogenetics holds significant potential for advancing neuromodulation. Continued research and technological innovations will further expand its role, offering new possibilities for understanding and treating disorders involving the peripheral nervous system. [ABSTRACT FROM AUTHOR]

The main objective of this review is to demonstrate the use of Peripheral Percutaneous Electrical Nerve Stimulation (PENS), together with its most up-to-date protocols, for the treatment of neuropathies. We conducted a systematic search for randomised clinical trials evaluating the effectiveness of PENS on pain intensity, sleep quality, oral analgesic intake and depression in patients with neuropathic pain. The search was performed in Pubmed, PEDro and Cochrane databases. The meta-analysis was conducted using RevMan 5.4 software. The mean difference was applied for variables with the same measurement scale, while the standardized mean difference was used for different scales. The inverse variance method was employed for statistical analysis, with heterogeneity assessed using the I² and Cochrane Q statistics. Four articles that met the search requirements were included. After qualitative and quantitative synthesis, the results obtained were an improvement in pain intensity (−3.57 [−4.01, −3.13]; p <.05) and sleep quality (2.48 [1.96, 3.00]; p <.05) and a reduction in medication intake (−2.37 [−4.26, −0.47]; p <.05) and depressive behaviours (−1.10 [−1.55, −0.66]; p <.05). The overall methodological quality was rated as moderate and the risk of bias as unclear. The scientific evidence found is still limited for the use of PENS in neuropathies. However, this study suggests an encouraging future for the use of this therapy as a treatment tool in physiotherapy. PENS requires nurse education on electrode/needle placement and patient instruction, with documentation of key parameters. This review emphasizes the need for further research to establish standardized protocols and optimal application parameters for different neuropathic pain conditions. [ABSTRACT FROM AUTHOR]

The study aims to evaluate the efficacy of neuromodulatory strategies for people who have drug-resistant epilepsy (DRE). We searched electronic repositories, including PubMed, Web of Science, Embase, and the Cochrane Library, for randomized controlled trials, their ensuing open-label extension studies, and prospective studies focusing on surgical or neuromodulation interventions for people with DRE. We used seizure frequency reduction as the primary outcome. A single-arm meta-analysis synthesized data across all studies to assess treatment effectiveness at multiple time points. A network meta-analysis evaluated the efficacy of diverse therapies in randomized controlled trials. Grading of Recommendations, Assessment, Development, and Evaluations was applied to evaluate the overall quality of the evidence. Twenty-eight studies representing 2936 individuals underwent 10 treatments were included. Based on the cumulative ranking in the network meta-analysis, the top 3 neuromodulatory options were deep brain stimulation (DBS) with 27% probability, responsive neurostimulation (RNS) with 22.91%, and transcranial direct current stimulation with 24.31%. In the single-arm meta-analysis, in the short-to-medium term, seizure control is more effective with RNS than with invasive vagus nerve stimulation (inVNS), which in turn is slightly more effective than DBS, though the differences are minimal. However, in the long term, inVNS appears to be less effective than both DBS and RNS. Trigeminal nerve stimulation, transcranial magnetic stimulation, and transcranial alternating current stimulation did not demonstrate significant seizure frequency reduction. Regarding long-term efficacy, RNS and DBS outperformed inVNS. While transcranial direct current stimulation and transcutaneous auricular VNS showed promise for treating DRE, further studies are needed to confirm their long-term efficacy. [ABSTRACT FROM AUTHOR]

Emerging neurostimulation methods aim to selectively modulate deep brain structures. Guiding these therapies has presented a substantial challenge, since imaging modalities such as MRI limit the spectrum of beneficiaries. In this study, we assess the guidance accuracy of a neuronavigation method that does not require taking MRI scans. The method is based on clearly identifiable anatomical landmarks of each subject's face. We compared this technique to the ideal case, MRI-based nonlinear brain registration, and evaluated the accuracy of both methods across ten targets located in deep brain structures: 7 targets in the anterior cingulate cortex as well as the anterior commissure and posterior commissure. Compared with the ideal case, the average localization error of the MRI-free method was 5.75 ± 2.98 mm (mean ± sd). These findings suggest that this method may provide sufficient compromise between practicality and the accuracy of targeting deep brain structures. [ABSTRACT FROM AUTHOR]

Appropriate social behaviors are imperative for the survival of many species and are maintained through positive reinforcement of affiliative social interactions. Despite similarities between social and nonsocial reward-seeking behavior, less is known regarding the neural circuits underlying social reward-related behaviors. Recent studies in rodents have used social behavioral paradigms to dissect the neural circuits that mediate various components of social behavior. These studies implicate the mesolimbic reward system and dopamine signaling in supporting the positive reinforcement of affiliative social interactions. Other neuromodulatory systems have also been implicated in social reward-seeking behavior. The neural mechanisms that drive affiliative social interactions are shaped by the internal state of the animal, including thirst, hunger, and social isolation. Across species, social behaviors are shaped and maintained through positive reinforcement of affiliative social interactions. As with nonsocial rewards, the reinforcing properties of social interactions have been shown to involve interplay between various brain regions and the mesolimbic reward system. In this review, we summarize findings from rodent research on the neural circuits that encode and mediate different components of social reward-seeking behavior. We explore methods to parse and study social reward-related behaviors using available behavioral paradigms. We also compare the neural mechanisms that support social versus nonsocial reward-seeking. Finally, we discuss how internal state and neuromodulatory systems affect reward-seeking behavior and the neural circuits that underlie social reward. [ABSTRACT FROM AUTHOR]

Responsive neurostimulation (RNS) is used off-label in pediatric patients with drug-resistant epilepsy (DRE). Our study aims to assess the safety and efficacy of RNS in pediatric and young adult patients with focal, multifocal, and generalized DRE. All patients who underwent RNS implantation at Primary Children's Hospital in Salt Lake City, UT, between December 2017 and 2022. A total of 47 patients were retrospectively identified, of which 32 patients were included in the final analysis. Patients ranged in age from five to 21 years (pediatric n = 22, young adult n = 10) at the time of RNS implantation with focal (20 [63%]), multifocal (8 [25%]), and generalized (4 [12%]) DRE. Operative complications (3 [9%]) and negative side effects (6 [19%]) were minor. At the time of most recent clinic visit (mean 18.6 months, S.D. 13.9), 19 of 32 patients (59%) were responders with ≥50% reduction in seizure frequency (pediatric n = 14, young adult n = 5). The rate of responders increased with prolonged activation of RNS stimulation, reaching 71% (five of seven patients) after 24 months. Antiseizure medication was reduced in five (16%) patients, and seizure rescue medication usage was reduced in 10 (31%) patients. Quality of life improved in 15 (47%) patients. RNS implantation resulted in a sustained reduction in seizure frequency with minimal side effects in a majority of patients. Taken together, our data suggest that RNS is an effective and safe treatment option for focal, multifocal, and potentially generalized DRE in the pediatric and young adult population. [ABSTRACT FROM AUTHOR]

• fMRI neurofeedback modulates BOLD signal in depression, in a single session. • Neurofeedback changes connectivity in key neural networks of depression. • A control group is vital for assessing neurofeedback's efficacy. Functional magnetic resonance imaging (fMRI) neurofeedback has emerged as a potential treatment modality for depression, but little is known about its mechanism of action. This study aims to investigate the efficacy of fMRI neurofeedback in modulating neural networks in depression. Following PRISMA guidelines, a systematic review was conducted focusing on fMRI neurofeedback interventions in depression. A comprehensive search across multiple databases yielded 16 eligible studies for review. The review demonstrated that fMRI neurofeedback can modulate BOLD activity even in strategy-free protocols and within a single session, with a significant learning effect evident over sessions. Neurofeedback targeting specific regions led to changes in connectivity across broad neural networks, including the default-mode and executive control networks, with effects being region-specific. However, methodological diversity and the absence of standardized protocols in the reviewed studies highlighted the need for more uniform research approaches. fMRI neurofeedback shows promise as a modulatory technique for depression, with the potential to induce significant changes in neural activity and connectivity of networks implicated in depression. The review underscores the necessity for standardized, reproducible neurofeedback protocols with control groups to enhance research comparability and generalizability. [ABSTRACT FROM AUTHOR]

• tDCS did not alter the corticomotor and intracortical excitability of the motor cortex in 105 healthy subjects. • Ipsilateral scalp cooling did not affect the motor excitability measured with SICI, ICF and single-pulse TMS. • Fixed-effects and mixed-effects model analysis resulted in distinct tDCS outcomes. Scalp cooling might increase the long-term potentiation (LTP)-like effect of transcranial direct current stimulation (tDCS) by reducing the threshold for after-effects according to metaplasticity and increasing electrical current density reaching the cortical neurons. We aimed to investigate whether priming scalp cooling potentiates the tDCS after-effect on motor cortex excitability. This study had a randomized, parallel-arms, sham-controlled, double-blinded design with an adequately powered sample of 105 healthy subjects. Corticomotor and intracortical excitability were assessed with motor evoked potentials (MEP) from transcranial magnetic stimulation (TMS) in short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) paradigms. Subjects were randomly allocated into six intervention groups, including anodal and cathodal tDCS (1-mA/20-min), scalp cooling, and sham. MEPs were recorded before, immediately, and 15 min after the interventions. We did not observe changes in MEP amplitude from single-pulse TMS, SICI, and ICF with any intervention protocol. Anodal and cathodal tDCS did not have an LTP-like neuromodulatory effect on corticospinal and did not provide detectable GABAergic and glutamatergic neurotransmission changes, which were not influenced by priming scalp cooling. We provide strong evidence that tDCS (1-mA/20-min) does not alter corticomotor and intracortical excitability with or without priming scalp cooling. [ABSTRACT FROM AUTHOR]

• A literature review showed that current low frequency repetitive transcranial magnetic stimulation (rTMS) protocols are not standardised. • A transient functional improvement without severe side effects has been reported by patients with epilepsia partialis continua after rTMS. • rTMS did not decrease EEG epileptiform discharges. Epilepsia Partialis Continua (EPC) is a challenging condition in which repetitive transcranial magnetic stimulation (rTMS) can induce a neuromodulation effect of potential diagnostic and therapeutic value. A comprehensive literature search was conducted using Pubmed and Web of Science databases to identify cases of EPC who underwent rTMS, including children and adults. Additionally, we present two patients from our centre who underwent rTMS at a low frequency (0.5 Hz) with simultaneous EEG recording with the aim of assessing potential improvement in seizure frequency and severity. Eight articles were selected comprising 16 patients (15 with EPC and one with continuous myoclonia). In three of these patients, no clinical or EEG changes were noted; the remaining cases showed transitory clinical improvements. We report two patients with EPC, in whom low frequency rTMS was associated with transient reduction in frequency and severity of seizures and improvements in hand function and dexterity. In one of these cases, rTMS suggested a potential target for intracranial recordings, subacute cortical stimulation and localised resection. In selected patients with EPC, rTMS can be used as a potential diagnostic and therapeutic tool. [ABSTRACT FROM AUTHOR]

• Seizure control is critical for pediatric patients with drug-resistant epilepsy. • Vagus nerve stimulation (VNS) therapy can be used when surgery is not possible. • A consensus expert opinion on use of VNS in pediatric patients was developed. • Recommendations for how to optimize VNS therapy in this population reached consensus. • The expert opinion can serve as a guideline for best-practice use of VNS. To provide consensus-based recommendations for use of vagus nerve stimulation (VNS) therapy in the management of pediatric epilepsy. Delphi methodology with two rounds of online survey was used to build consensus. A steering committee developed 43 statements related to pediatric epilepsy and the use of VNS therapy, which were evaluated by a panel of 12 neurologists/neurosurgeons with expertise in pediatric epilepsy, who graded their agreement with each statement on a scale of 1 ("I do not agree at all") to 5 ("I strongly agree"). For each statement, consensus was established if ≥70% of the agreement scores were 4 or 5 and <30% were 1 or 2 in the final survey. Twenty-four statements regarding the need for seizure reduction in pediatric epilepsy, the recommended treatment algorithm, the benefits and safety of VNS therapy, management of side effects of VNS therapy, patient selection for VNS therapy, and the use, dosing, and titration of VNS therapy achieved consensus. VNS and other neuromodulation therapies should be considered for pediatric patients with drug-resistant epilepsy who are not candidates for resective surgery, or who do not remain seizure free after resective surgery. When VNS therapy is initiated, the target dose range should be achieved via the fastest and safest titration schedule for each patient. Scheduled programming can be helpful in dose titration. The expert consensus statements represent the panelists' collective opinion on the best practice use of VNS therapy to optimize outcomes in the management of pediatric epilepsy. [ABSTRACT FROM AUTHOR]

Stress-related disorders constitute a fast-progressing worldwide societal problem that needs urgent attention and new solutions. Recent neuroscientific research has shown that stress-related disorders are characterized by maladaptive dynamic changes in large-scale brain networks in response to stressors, raising the possibility of modulating these networks as a promising target for intervention. Neurofeedback can be used to train individuals to endogenously modulate brain network dynamics. Once learned, this skill is transferrable to ecologically relevant scenarios outside of a laboratory or treatment facility, and individuals can be trained to explicitly apply it at the right moments as part of a just-in-time adaptive intervention in response to actual stressors in daily life. We argue that these characteristics position neurofeedback as a prime candidate for a personalized preventive neuroscience-based intervention strategy. Stress-related disorders are among the biggest global health challenges. Despite significant progress in understanding their neurocognitive basis, the promise of applying insights from fundamental research to prevention and treatment remains largely unfulfilled. We argue that neurofeedback – a method for training voluntary control over brain activity – has the potential to fill this translational gap. We provide a contemporary perspective on neurofeedback as endogenous neuromodulation that can target complex brain network dynamics, is transferable to real-world scenarios outside a laboratory or treatment facility, can be trained prospectively, and is individually adaptable. This makes neurofeedback a prime candidate for a personalized preventive neuroscience-based intervention strategy that focuses on the ecological momentary neuromodulation of stress-related brain networks in response to actual stressors in real life. [ABSTRACT FROM AUTHOR]

There is a significant unmet need for safe and effective nonpharmacological therapies for restless legs syndrome (RLS). The objective was to evaluate the efficacy and safety of tonic motor activation (TOMAC) in patients with RLS. A multicenter, randomized, participant-blinded, sham-controlled trial enrolled 45 adults with primary moderate-to-severe RLS who were either medication-naïve (n = 20) or medication-refractory (n = 25). Participants were 1:1 randomized to TOMAC (n = 22) or sham (n = 23) for two weeks and instructed to self-administer 30-min TOMAC sessions when they experienced RLS symptoms. The primary outcome was mean change in International RLS Study Group Rating Scale (IRLS) total score. A subsequent meta-analysis included the present trial and a previous randomized clinical trial that enrolled medication-naïve RLS patients. IRLS reduction was significantly greater for TOMAC than sham (TOMAC -6.59 vs. sham −2.17; mean difference (MD) = −4.42; 95 % confidence interval [CI] −1.57 to −7.26; p = 0.0040). Subgroup analysis showed similar IRLS mean difference for medication-refractory (MD = −4.50; p = 0.02) and medication-naïve (MD = −4.40; p = 0.08) cohorts, which was significantly different from sham only for the medication-refractory cohort. Meta-analysis of combined data from 33 medication-naïve RLS patients showed a significant reduction in mean IRLS score after two weeks for TOMAC compared to sham (MD = −4.30; 95 % CI -1.36 to −7.24; p = 0.004). The present trial confirmed previous reports documenting efficacy and safety of TOMAC in refractory RLS and indicated similar effect sizes in refractory versus naïve subgroups. The meta-analysis demonstrated that TOMAC significantly improves RLS symptoms in naïve participants. • Tonic motor activation (TOMAC) reduces restless legs syndrome (RLS) symptoms. • TOMAC is efficacious for both medication-refractory and -naïve RLS patients. • TOMAC is safe and well tolerated. [ABSTRACT FROM AUTHOR]

To evaluate if acute intermittent hypoxia (AIH) coupled with transcutaneous spinal cord stimulation (tSCS) enhances task-specific training and leads to superior and more sustained gait improvements as compared with each of these strategies used in isolation in persons with chronic, incomplete spinal cord injury. Proof of concept, randomized crossover trial. Outpatient, rehabilitation hospital. Ten participants completed 3 intervention arms: (1) AIH, tSCS, and gait training (AIH + tSCS); (2) tSCS plus gait training (SHAM AIH + tSCS); and (3) gait training alone (SHAM + SHAM). Each arm consisted of 5 consecutive days of intervention with a minimum of a 4-week washout between arms. The order of arms was randomized. The study took place from December 3, 2020, to January 4, 2023. 10-meter walk test at self-selected velocity (SSV) and fast velocity, 6-minute walk test, timed Up and Go (TUG) and secondary outcome measures included isometric ankle plantarflexion and dorsiflexion torque TUG improvements were 3.44 seconds (95% CI: 1.24-5.65) significantly greater in the AIH + tSCS arm than the SHAM AIH + tSCS arm at post-intervention (POST), and 3.31 seconds (95% CI: 1.03-5.58) greater than the SHAM + SHAM arm at 1-week follow up (1WK). SSV was 0.08 m/s (95% CI: 0.02-0.14) significantly greater following the AIH + tSCS arm than the SHAM AIH + tSCS at POST. Although not significant, the AIH + tSCS arm also demonstrated the greatest average improvements compared with the other 2 arms at POST and 1WK for the 6-minute walk test, fast velocity, and ankle plantarflexion torque. This pilot study is the first to demonstrate that combining these 3 neuromodulation strategies leads to superior improvements in the TUG and SSV for individuals with chronic incomplete spinal cord injury and warrants further investigation. [ABSTRACT FROM AUTHOR]

Memory consolidation requires rapid energy supply to neurons. In a recent study, Francés et al. revealed the signal by which a neuron commands glia to limit fatty acid synthesis in favor of metabolite export during memory formation in Drosophila melanogaster. This mechanism coordinates just-in-time glial energy delivery in response to dynamic neuronal needs. [ABSTRACT FROM AUTHOR]

The zona incerta (ZI) is a subcortical structure primarily investigated in rodents that is implicated in various behaviors, ranging from motor control to survival-associated activities, partly due to its integration in multiple neural circuits. In the current study, we used diffusion magnetic resonance imaging tractography to segment the ZI and gain insight into its connectivity in various circuits in humans. We performed probabilistic tractography in 7T diffusion MRI on 178 participants from the Human Connectome Project to validate the ZI's anatomical subdivisions and their respective tracts. K-means clustering segmented the ZI based on each voxel's connectivity profile. We further characterized the connections of each ZI subregion using probabilistic tractography with each subregion as a seed. We identified 2 dominant clusters that delineated the whole ZI into rostral and caudal subregions. The caudal ZI primarily connected with motor regions, while the rostral ZI received a topographic distribution of projections from prefrontal areas, notably the anterior cingulate and medial prefrontal cortices. We generated a probabilistic ZI atlas that was registered to a patient-participant's magnetic resonance imaging scan for placement of stereoencephalographic leads for electrophysiology-guided deep brain stimulation to treat their obsessive-compulsive disorder. Rostral ZI stimulation improved the patient's core symptoms (mean improvement 21%). We present a tractography-based atlas of the rostral and caudal ZI subregions constructed using high-resolution diffusion magnetic resonance imaging from 178 healthy participants. Our work provides an anatomical foundation to explore the rostral ZI as a novel target for deep brain stimulation to treat refractory obsessive-compulsive disorder and other disorders associated with dysfunctional reward circuitry. [ABSTRACT FROM AUTHOR]

One of the most common applications of transcranial electrical stimulation (tES) at low current intensity is to induce a relaxed state or reduce anxiety. With technical advancement, different waveforms, montages, and parameters can be incorporated into the treatment regimen. We developed a novel protocol to treat individuals with anxiety disorders by transcranial alternating current stimulation (tACS). A total of 27 individuals with anxiety disorders underwent tACS treatment for 12 sessions, with each session lasting 25 min. tACS at 5 Hz was applied to F4 (1.0 mA), P4 (1.0 mA), and T8 (2.0 mA) EEG lead positions (tripod), with sinewave oscillation between T8 and F4/P4. We evaluated the primary and secondary outcomes using the Beck Anxiety Inventory (BAI) and neuropsychological assessments. Of the 27 patients, 19 (70.4 %) experienced a reduction in symptom severity >50 %, with an average reduction of BAI 58.5 %. All reported side effects were mild, with itching or tingling being the most common complaint. No significant differences were noted in attention, linguistic working memory, visuospatial working memory, or long-term memory in neuropsychological assessments. The results suggest the potential of this novel tripod tACS design as a rapid anxiety alleviator and the importance of a clinical trial to verify its efficacy. • Transcranial alternating current stimulation (tACS) was applied to treat anxiety disorders. • tACS at 5 Hz was applied to F4 (1 mA), P4 (1 mA), and T8 (2 mA) EEG lead positions (tripod), with the sinewave oscillation between T8 and F4/P4. • Following 12 treatment sessions, the reduction of symptoms amounted to 58.5%, and 70.4% of participants responded positively. • The tripod tACS design could be a rapid anxiety alleviator. [ABSTRACT FROM AUTHOR]

Magnetic stimulation, represented by transcranial magnetic stimulation (TMS), is used to treat neurological diseases. Various strategies have been explored to improve the spatial resolution of magnetic stimulation. While reducing the coil size is the most impactful approach for increasing the spatial resolution, it decreases the stimulation intensity and increases heat generation. We aim to demonstrate the feasibility of magnetic stimulation using an epidurally implanted millimeter-sized coil and that it does not damage the cortical tissue via heating even when a repetitive stimulation protocol is used. A coil with dimensions of 3.5 × 3.5 × 2.6 mm3 was epidurally implanted on the left motor cortex of rat, corresponding to the right hindlimb. Before and after epidural magnetic stimulation using a quadripulse stimulation (QPS) protocol, changes in the amplitude of motor evoked potentials (MEPs) elicited by a TMS coil were compared. The experimental group showed an average increase of 88 % in MEP amplitude in the right hindlimb after QPS, whereas the MEP amplitude in the left hindlimb increased by 18 % on average. The control group showed no significant change in MEP amplitude after QPS in either hindlimb. The temperature changes at the coil surface remained <2 °C during repetitive stimulation, meeting the thermal safety limit for implantable medical devices. These results demonstrate the feasibility of epidural magnetic stimulation using an implantable coil to induce neuromodulation effects. This novel method is expected to be a promising alternative for focal magnetic stimulation with an improved spatial resolution and lowered stimulus current than previous magnetic stimulation methods. • Focal magnetic stimulation of the brain was achieved by implanting a mm-sized coil epidurally. • Epidural magnetic stimulation modulated the amplitude of motor evoked potentials (MEPs), though not directly evoking MEPs. • Heat generation during epidural magnetic stimulation was managed to remain within the thermal safety limit. [ABSTRACT FROM AUTHOR]

Non-invasive deep brain modulation (DBM) stands as a promising therapeutic avenue to treat brain diseases. Acoustic DBM represents an innovative and targeted approach to modulate the deep brain, employing techniques such as focused ultrasound and shock waves. Despite its potential, the optimal mechanistic parameters, the effect in the brain and behavioral outcomes of acoustic DBM remains poorly understood. To establish a robust protocol for the shock wave DBM by optimizing its mechanistic profile of external stimulation, and to assess its efficacy in preclinical settings. We used shockwaves due to their capacity to leverage a broader spectrum of peak intensity (10–127 W/mm2) in contrast to ultrasound (0.1–5.0 W/mm2), thereby enabling a more extensive range of neuromodulation effects. We established various types of shockwave pressure profiles of DBM and compared neural and behavioral responses. To ascertain the anticipated cause of the heightened neural activity response, numerical analysis was employed to examine the mechanical dynamics within the brain. An optimized profile led to an enhancement in neuronal activity within the hypothalamus of mouse models. The optimized profile in the hippocampus elicited a marked increase in neurogenesis without neuronal damage. Behavioral analyses uncovered a noteworthy reduction in locomotion without significant effects on spatial memory function. The present study provides an optimized shock wave stimulation protocol for non-invasive DBM. Our optimized stimulation profile selectively triggers neural functions in the deep brain. Our protocol paves the way for new non-invasive DBM devices to treat brain diseases. • Neural activity depended on the mechanistic profile of external stimulation. • c-Fos density and pressure gradient were both highly concentrated in hypothalamus. • Optimal stimuli increased neuronal activation and its concentration in the thalamus. • Optimal stimuli elicited a marked increase in neurogenesis without neuronal damage. [ABSTRACT FROM AUTHOR]

Cardiac control is mediated via nested-feedback reflex control networks involving the intrinsic cardiac ganglia, intra-thoracic extra-cardiac ganglia, spinal cord, brainstem, and higher centers. This control system is optimized to respond to normal physiologic stressors; however, it can be catastrophically disrupted by pathologic events such as myocardial ischemia. In fact, it is now recognized that cardiac disease progression reflects the dynamic interplay between adverse remodeling of the cardiac substrate coupled with autonomic dysregulation. With advances in understanding of this network dynamic in normal and pathologic states, neuroscience-based neuromodulation therapies can be devised for the management of acute and chronic cardiac pathologies. [ABSTRACT FROM AUTHOR]

The contemporary history of the cardiac autonomic nervous system includes early descriptions of neuroanatomy in the 19th century, followed by an understanding of the physiologic determinants of neurocardiology in the 20th century. Neurology and cardiology preceded the arrival of clinical cardiac electrophysiology, a specialized field in medicine devoted to the diagnosis and treatment of cardiac arrhythmias. The rapid growth in pharmacology, ablation, pacing and defibrillation, associated with significant technological breakthroughs, have resulted in new opportunities for neuromodulation in the 21st century. Small changes in autonomic tone can potentially provide important therapeutic benefits for patients with cardiac and arrhythmia disorders. [ABSTRACT FROM AUTHOR]

The cardiac autonomic nervous system plays a key role in maintaining normal cardiac physiology, and once disrupted, it worsens the cardiac disease states. Neuromodulation therapies have been emerging as new treatment options, and various techniques have been introduced to mitigate autonomic nervous imbalances to help cardiac patients with their disease conditions and symptoms. In this review article, we discuss various neuromodulation techniques used in clinical settings to treat cardiac diseases. [ABSTRACT FROM AUTHOR]

Transcranial direct current stimulation (tDCS) is a safe, accessible, and promising therapeutic approach for obsessive-compulsive disorder (OCD). This study aimed to evaluate the effect of tDCS on electroencephalography (EEG) microstates and identify potential biomarkers to predict efficacy. A total of 24 individuals diagnosed with OCD underwent ten sessions of tDCS targeting the orbitofrontal cortex, while 27 healthy individuals were included as controls. Microstates A, B, C, and D were extracted before and after tDCS. A comparative analysis of microstate metrics was performed between the OCD and the healthy control groups, as well as within the OCD group before and after tDCS. Multiple linear regression analysis was performed to identify potential biomarkers of tDCS. Comparison to healthy controls, the OCD group exhibited a significantly reduced duration of microstate A and increased occurrence of microstate D. The transition between microstates A and C was significantly different between patients with OCD and healthy controls and was no longer observed following tDCS. Multiple linear regression analysis revealed that the duration of microstate C was associated with an improvement OCD symptom after tDCS. The results revealed an aberrant large-scale EEG brain network that could be modulated by tDCS. In particular, the duration of EEG microstate C may be a neurophysiological characteristic associated with the therapeutic effects of tDCS on OCD. • Patients with OCD showed a decrease in the duration of microstate A and an increase in the occurrence of microstate D. • tDCS could modulate large-scale EEG brain network in OCD. • The duration of EEG microstate C may be a neurophysiological characteristic associated with the therapeutic effects of tDCS on OCD. [ABSTRACT FROM AUTHOR]

Functional neurosurgery involves the surgical management of a wide range of neurological diseases with the aim of treating conditions such as movement disorders, spasticity, epilepsy and intractable pain. Functional neurosurgery began with ablative surgical techniques involving destruction of neural structures responsible for the aberrant neural pathways/networks causing pathology. In more recent years there has been a move away from the creation of permanent destructive lesions towards modulation of the neural networks utilizing neuro-modulation. Neuromodulation therapies include invasive (e.g. deep brain stimulators, cortical stimulators, vagal nerve stimulators and spinal cord stimulators) and non-invasive (e.g. transcranial magnetic stimulation) approaches that involve the application of electrical stimulation to drive or inhibit neural function within a circuit. Most implantable neuromodulation systems include three primary components: stimulating electrode(s) with contacts at the tip through which electricity is delivered, an implantable pulse generator (IPG) that serves as a signal generator/battery pack, and the extension cable(s) to subcutaneously connect the electrode(s) to the IPG. In this article we primarily focus on the current role of neuromodulation in treating movement disorders, epilepsy and pain, and also consider emerging and evolving applications. [ABSTRACT FROM AUTHOR]

• Meticulous presurgical evaluation and the selection of appropriate surgical procedure can effectively control seizure to a certain extent. • Pooled outcomes of resective surgery showed that 74 % of patients achieved Engel I at the last follow-up. • Pooled outcomes of neurostimulation showed that 9 % patients achieved seizure free and 61 % of patientsachieved 50 % reduction in seizure frequency at the last follow-up. • Univariate analysis indicated that being female, having somatic mutations, and presenting with focal seizure symptoms were associated with a better prognosis. To summarize the surgical outcomes of genetically refractory epilepsy and identify prognostic factors for these outcomes. A literature search of the PubMed, Web of Science, and Embase databases for relevant studies, published between January 1, 2002 and December 31, 2023, was performed using specific search terms. All studies addressing surgical outcomes and follow-up of genetically refractory epilepsy were included. All statistical analyses were performed using STATA software (StataCorp LLC, College Station, TX, USA). This review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, 2020 (i.e., "PRISMA") reporting guidelines. Of the 3833 studies retrieved, 55 fulfilled the inclusion criteria. Eight studies were eligible for meta-analysis at the study level. Pooled outcomes revealed that 74 % of patients who underwent resective surgery (95 % confidence interval [CI] 0.55–0.89; z = 9.47, p < 0.05) achieved Engel I status at the last follow-up. In the study level analysis, pooled outcomes revealed that 9 % of patients who underwent vagus nerve stimulation achieved seizure-free status (95 % CI 0.00–0.31; z = 1.74, p < 0.05), and 61 % (95 % CI 0.55–0.89; z = 11.96, p < 0.05) achieved a 50 % reduction in seizure frequency at the last follow-up. Fifty-three studies comprising 249 patients were included in an individual-level analysis. Among patients who underwent lesion resection or lobectomy/multilobar resection, 65 % (100/153) achieved Engel I status at the last follow-up. Univariate analysis indicated that female sex, somatic mutations, and presenting with focal seizure symptoms were associated with better prognosis (p < 0.05). Additionally, 75 % (21/28) of patients who underwent hemispherectomy/hemispherotomy achieved Engel I status at the last follow-up. In the individual-level analysis, among patients treated with vagus nerve stimulation, 21 % (10/47) were seizure-free and 64 % (30/47) experienced >50 % reduction in seizure frequency compared with baseline. Meticulous presurgical evaluation and selection of appropriate surgical procedures can, to a certain extent, effectively control seizures. Therefore, various surgical procedures should be considered when treating patients with genetically refractory epilepsy. [ABSTRACT FROM AUTHOR]

Neuromodulatory interventions are relatively novel and approaches to studying harms and tolerability have varied. Using a checklist based on guidelines from Good Clinical Practice and the Harms Extension of the CONSORT (Consolidated Standards of Reporting Trials) Statement, we identified how adverse events are measured, assessed, and reported in studies evaluating neuromodulation for the treatment of mental and neurodevelopmental disorders among children and adolescents. A systematic literature review identified 56 experimental and quasi-experimental studies evaluating transcranial magnetic stimulation (TMS), transcranial alternating (tACS) or direct (tDCS) current stimulation, transcranial pulse stimulation (TPS), and vagus or trigeminal nerve stimulation (VNS or TNS). For 22 studies (39%), the types of adverse events to be monitored were identified, and for 31 studies (55%), methods for collecting adverse event data were described. Methods for assessing adverse events were less commonly described with 23 studies (41%) having details on assessing event severity, and 11 studies (20%) having details on assessing event causality. Among 31 studies with reported results, headache, skin irritation, and general pain or discomfort were the most reported across studies. Seizure, untoward medical occurrences, and intracranial bleeding, edema, or other intracranial pathology were considered serious events, but these events were not reported as occurring in any results-based papers. Taken together, the findings from this review indicate that most studies of pediatric neuromodulatory interventions did not include descriptions of adverse event monitoring and evaluation. Comprehensive event monitoring and reporting across studies can significantly augment the current knowledge base. [ABSTRACT FROM AUTHOR]