Readers frequently encounter homographs (e.g., bank) whose resolution requires selection-suppression processes: selecting the contextually relevant meaning, while suppressing the irrelevant one. In two experiments, we investigated how these processes are modulated by the phonological status of the homograph (homographs with one vs. two possible pronunciations); and what is the involvement of the left inferior frontal gyrus (LIFG, including Broca\'s area) in these processes. To these ends, Experiment 1 utilized the context verification task with two types of Hebrew homographs: homophonic (e.g., bank) and heterophonic (e.g., tear). In the task, participants read sentences ending either with a homograph (e.g., bank) or an unambiguous word (e.g., shore). The sentences were biased towards the homograph\'s subordinate meaning (e.g., The fisherman sat on the bank/shore), and were followed by a target word related to the homograph\'s dominant meaning (e.g., MONEY). The participants were asked to judge whether the target was related to the overall meaning of the sentence. An ambiguity effect was observed for both types of homographs, reflecting interference from the irrelevant dominant meaning. However, this ambiguity effect was larger for heterophonic than for homophonic homographs, indicating that dominant meanings of heterophonic homographs are more difficult to suppress. Experiment 2 was identical, except that the procedure was coupled with transcranial direct current stimulation (tDCS) over the LIFG (including Broca\'s area). We found that stimulating the LIFG abolished the ambiguity effect, but only in the case of heterophonic homographs. Together, these findings highlight the distinction between phonological and semantic levels of selection-suppression processes, and the involvement of the LIFG in the phonological level of these processes.

BACKGROUND: Transcranial magnetic stimulation (TMS) interventions could feasibly treat stroke-related motor impairments, but their effects are highly variable. Brain state-dependent TMS approaches are a promising solution to this problem, but inter-individual variation in lesion location and oscillatory dynamics can make translating them to the poststroke brain challenging. Personalized brain state-dependent approaches specifically designed to address these challenges are therefore needed.
METHODS: As a first step towards this goal, we tested a novel machine learning-based EEG-TMS system that identifies personalized brain activity patterns reflecting strong and weak corticospinal tract (CST) output (strong and weak CST states) in healthy adults in real-time. Participants completed a single-session study that included the acquisition of a TMS-EEG-EMG training dataset, personalized classifier training, and real-time EEG-informed single pulse TMS during classifier-predicted personalized CST states.
RESULTS: MEP amplitudes elicited in real-time during personalized strong CST states were significantly larger than those elicited during personalized weak and random CST states. MEP amplitudes elicited in real-time during personalized strong CST states were also significantly less variable than those elicited during personalized weak CST states. Personalized CST states lasted for ~1-2 seconds at a time and ~1 second elapsed between consecutive similar states. Individual participants exhibited unique differences in spectro-spatial EEG patterns between personalized strong and weak CST states.
CONCLUSIONS: Our results show for the first time that personalized whole-brain EEG activity patterns predict CST activation in real-time in healthy humans. These findings represent a pivotal step towards using personalized brain state-dependent TMS interventions to promote poststroke CST function.

BACKGROUND: Awareness is a state of consciousness that enables a subject to interact with the environment. Transient alteration of awareness (AA) is a disabling sign of many types of epileptic seizures. The brain mechanisms of awareness and its alteration are not well known.
OBJECTIVE: Transient and isolated AA induced by electrical brain stimulation during a stereoelectroencephalography (SEEG) recording represents an ideal model for studying the associated modifications of functional connectivity and locating the hubs of awareness networks.
METHODS: We investigated the SEEG signals-based brain functional connectivity (FC) changes vs background occurring during AA triggered by three thalamic and two insular stimulations in three patients explored by SEEG in the frame of presurgical evaluation for focal drug-resistant epilepsy. The results were compared to the stimulations of the same sites that did not induce clinical changes (negative stimulations).
RESULTS: We observed decreased node strength in the pulvinar, insula, and parietal associative cortices during the thalamic and insular stimulations that induced AA. The link strengths characterizing functional coupling between the thalamus and the insular, prefrontal, temporal, or parietal associative cortices were also decreased. In contrast, there was an increased synchronization between the precuneus and the temporal lateral cortex. These FC changes were absent during the negative stimulations.
CONCLUSIONS: Our study highlights the role of the pulvinar, insular, and parietal hubs in maintaining the awareness networks and paves the way for invasive or non-invasive neuromodulation protocols to reduce AA manifestations during epileptic seizures.

BACKGROUND: 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.
OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.

Transcranial temporal interference stimulation (tTIS) is a promising brain stimulation method that can target deep brain regions by delivering an interfering current from surface electrodes. Most instances of tTIS stimulate the brain with a single-frequency sinusoidal waveform generated by wave interference. Theta burst stimulation is an effective stimulation scheme that can modulate neuroplasticity by generating long-term potentiation- or depression-like effects. To broaden tTIS application, we developed a theta burst protocol using tTIS technique to modulate neuroplasticity in rats. Two cannula electrodes were unilaterally implanted into the intact skull over the primary motor cortex. Electrical field of temporal interference envelopes generated by tTIS through cannula electrodes were recorded from primary motor cortex. Theta burst schemes were characterized, and motor activation induced by the stimulation was also evaluated simultaneously by observing electromyographic signals from the corresponding brachioradialis muscle. After validating the stimulation scheme, we further tested the modulatory effects of theta burst stimulation delivered by tTIS and by conventional transcranial electrical stimulation on primary motor cortex excitability. Changes in the amplitude of motor evoked potentials, elicited when the primary motor cortex was activated by electrical pulses, were measured before and after theta burst stimulation by both techniques. Significant potentiation and suppression were found at 15 to 30 min after the intermittent and continuous theta burst stimulation delivered using tTIS, respectively. However, comparing to theta burst stimulations delivered using conventional form of transcranial electrical stimulation, using tTIS expressed no significant difference in modulating motor evoked potential amplitudes. Sham treatment from both methods had no effect on changing the motor evoked potential amplitude. The present study demonstrated the feasibility of using tTIS to achieve a theta burst stimulation scheme for motor cortical neuromodulation. These findings also indicated the future potential of using tTIS to carry out theta burst stimulation protocols in deep-brain networks for modulating neuroplasticity.

UNASSIGNED: Transcranial alternating current stimulation (tACS) alters cortical excitability with low-intensity alternating current and thereby modulates aberrant brain oscillations. Despite the recent increase in studies investigating the feasibility and efficacy of tACS in treating neuropsychiatric disorders, its mechanisms, as well as optimal stimulation parameters, are not fully understood.
UNASSIGNED: This systematic review aimed to compile human research on tACS for neuropsychiatric disorders to delineate typical treatment parameters for these conditions and evaluate its outcomes.
UNASSIGNED: A search for published studies and unpublished registered clinical trials was conducted through OVID (MEDLINE, PsycINFO, and Embase), ClinicalTrials.gov, and the International Clinical Trials Registry Platform. Studies utilizing tACS to treat neuropsychiatric disorders in a clinical trial setting were included.
UNASSIGNED: In total, 783 published studies and 373 clinical trials were screened; 53 published studies and 70 clinical trials were included. Published studies demonstrated a low risk of bias, as assessed by the Joanna Briggs Institute Critical Appraisal Tools. Neurocognitive, psychotic, and depressive disorders were the most common disorders treated with tACS. Both published studies (58.5%) and registered clinical trials (52%) most commonly utilized gamma frequency bands and tACS was typically administered at an intensity of 2 mA peak-to-peak, once daily for 20 or fewer sessions. Although the targeted brain locations and tACS montages varied across studies based on the outcome measures and specific pathophysiology of the disorders, the dorsolateral prefrontal cortex (DLPFC) was the most common target in both published studies (30.2%) and registered clinical trials (25.6%). Across studies that published results on tACS outcome measures, tACS resulted in enhanced symptoms and/or improvements in overall psychopathology for neurocognitive (all 11 studies), psychotic (11 out of 14 studies), and depressive (7 out of 8 studies) disorders. Additionally, 17 studies reported alterations in the power spectrum of the electroencephalogram around the entrained frequency band at the targeted locations following tACS.
UNASSIGNED: Behavioral and cognitive symptoms have been positively impacted by tACS. The most consistent changes were reported in cognitive symptoms following gamma-tACS over the DLPFC. However, the paucity of neuroimaging studies for each neuropsychiatric condition highlights the necessity for replication studies employing biomarker- and mechanism-centric approaches.

Long COVID (Coronavirus disease), affecting millions globally, presents unprecedented challenges to healthcare systems due to its complex, multifaceted nature and the lack of effective treatments. This perspective review explores the potential of artificial intelligence (AI)-guided transcranial direct current stimulation (tDCS) as an innovative approach to address the urgent need for effective Long COVID management. The authors examine how AI could optimize tDCS protocols, enhance clinical trial design, and facilitate personalized treatment for the heterogeneous manifestations of Long COVID. Key areas discussed include AI-driven personalization of tDCS parameters based on individual patient characteristics and real-time symptom fluctuations, the use of machine learning for patient stratification, and the development of more sensitive outcome measures in clinical trials. This perspective addresses ethical considerations surrounding data privacy, algorithmic bias, and equitable access to AI-enhanced treatments. It also explores challenges and opportunities for implementing AI-guided tDCS across diverse healthcare settings globally. Future research directions are outlined, including the need for large-scale validation studies and investigations of long-term efficacy and safety. The authors argue that while AI-guided tDCS shows promise for addressing the complex nature of Long COVID, significant technical, ethical, and practical challenges remain. They emphasize the importance of interdisciplinary collaboration, patient-centered approaches, and a commitment to global health equity in realizing the potential of this technology. This perspective article provides a roadmap for researchers, clinicians, and policymakers involved in developing and implementing AI-guided neuromodulation therapies for Long COVID and potentially other neurological and psychiatric conditions.

Transcranial electrical brain stimulation techniques like transcranial direct current (tDCS) and transcranial alternating current (tACS) have emerged as potential tools for treating neurological diseases by modulating cortical excitability. These techniques deliver small electric currents to the brain non-invasively through electrodes on the scalp. tDCS uses constant direct current which weakly alters the membrane voltage of cortical neurons, while tACS utilizes alternating current to target and enhance cortical oscillations, though the underlying mechanisms are not fully understood more specifically. To elucidate how tACS perturbs endogenous network dynamics, we simulated spiking neuron network models. We identified distinct roles of the depolarizing and hyperpolarizing phases in driving network activity towards and away from the strong nonlinearity provided by pyramidal neurons. Exploring resonance effects, we found matching tACS frequency to the network\'s endogenous resonance frequency creates greater entrainment. Based on this, we developed an algorithm to determine the network\'s endogenous frequency, phase, and amplitude, then deliver optimized tACS to entrain network oscillations. Together, these computational results provide mechanistic insight into the effects of tACS on network dynamics and could inform future closed-loop tACS systems that dynamically tune stimulation parameters to ongoing brain activity.

BACKGROUND: Impairments in postural responses to perturbation are common in people with Parkinson\'s disease (PwPD) and lack effective treatment. We recently showed that a single session of transcranial direct current stimulation (tDCS) promotes acute improvement of postural response to perturbation in PwPD. However, the effects of multiple tDCS sessions remain unclear.
OBJECTIVE: What is the efficacy of eight sessions of anodal tDCS on postural responses to external perturbation in PwPD?
METHODS: Twenty-two PwPD participated in this randomized, double-blind, parallel-arm, and sham-controlled study. Participants were randomly distributed into active (a-tDCS; n=11) or sham stimulation (s-tDCS; n=11). Eight tDCS sessions were applied over the primary motor cortex (M1), with the a-tDCS group receiving 2 mA for 20 minutes. Postural responses to external perturbations were assessed before, 48 hours after, and one month after (follow-up) the completion of tDCS sessions. Primary outcome measures included the onset latency of medial gastrocnemius (MG) muscle and range of center of pressure. Secondary outcomes included electromyography and CoP parameters, and prefrontal cortex (PFC) activity.
RESULTS: ANOVA revealed a trend for Group*Moment interaction for MG onset latency (p=0.058). a-tDCS tended to have shorter MG onset latency at post-test (p=0.040; SRM = -0.63) compared to pre-test. For the secondary outcomes, only a-tDCS decreased the time taken to recover balance after the perturbation at post-test and follow-up compared to pre-test (both p<0.001; SRM=-1.42 and -1.53, respectively). Also, only a-tDCS demonstrated lower PFC activity at post-test compared to pre-test (p=0.017; SRM = -0.82) and follow-up (p=0.001).
CONCLUSIONS: Eight sessions of tDCS over M1 improved postural response to perturbation in PwPD. Some benefits lasted for at least a month. Neuromuscular and behavioral changes observed after the intervention were accompanied by decreased PFC activity (executive-attentional control), suggesting that tDCS applied over M1 can improve movement automaticity.

UNASSIGNED: Enhanced glutamatergic transmission leading to motor neuron death is considered the major pathophysiological mechanism of amyotrophic lateral sclerosis (ALS). Motor cortex excitability can be suppressed by transcranial static magnetic stimulation (tSMS), thus tSMS can be evaluated as a potential treatment for ALS. The aim of present study was to investigate the efficacy and safety of tSMS in ALS.
UNASSIGNED: In this phase 2 trial, we randomly assigned ALS patients to receive daily tSMS or placebo stimulation over a period of 6 months. For each participant we calculated mean disease monthly progression rate (MPR) as the variation of the total ALS Functional Rating Scale-Revised (ALSRFS-R) score, before the beginning of the treatment (over a period of at least three months) and over the six-month treatment period. The primary efficacy outcome was the difference in MPR before and after the beginning of treatment. Secondary outcomes included safety and tolerability, compliance, and changes in corticospinal output. A long-term follow-up of 18 months was performed in all patients who completed the six-month treatment considering a composite endpoint event (tracheostomy or death). Trial registered at ClinicalTrials.gov, ID: NCT04393467, status: closed.
UNASSIGNED: Forty participants were randomly assigned to real (n = 21) or placebo stimulation (n = 19). Thirty-two participants (18 real and 14 placebo) completed the 6-month treatment. The MPR did not show statistically significant differences between the two arms during the pre-treatment (mean ± Standard deviation; Real: 1.02 ± 0.62, Sham: 1.02 ± 0.57, p-value = 1.00) and treatment period (Real: 0.90 ± 0.55, Sham: 0.94 ± 0.55, p-value = 0.83). Results for secondary clinical endpoints showed that the treatment is feasible and safe, being compliance with tSMS high. The change in corticospinal output did not differ significantly between the two groups. At the end of the long-term follow-up of 18 months, patients of real group had a statistically significant higher tracheostomy-free survival compared with patients of placebo group (Hazard Ratio = 0.27 95% Confidence interval 0.09-0.80, p-value = 0.019).
UNASSIGNED: tSMS did not modify disease progression during the 6 months of treatment. However, long-term follow-up revealed a substantial increase in tracheostomy free survival in patients treated with real stimulation supporting the evaluation of tSMS in larger and more prolonged studies.
UNASSIGNED: The \"Fondazione \'Nicola Irti\' per le opere di carità e di cultura\", Rome, Italy, supported present study.