Inhibitory Stimulation Research Articles

Left ventromedial prefrontal cortex inhibitory rTMS as an anti-stress intervention in opioid use disorder: Trial design.

In people with substance use disorders (SUDs), stress-exposure can impair executive function, and increase craving and likelihood of drug-use recurrence. Research shows that acute stressors increase drug-seeking behavior; however, mechanisms underlying this effect are incompletely understood. The Competing Neurobehavioral Decisions System theory posits that persons with SUDs may have hyperactive limbic reward circuitry and hypoactive executive control circuitry. To investigate how inhibitory repetitive transcranial magnetic stimulation (rTMS) targeting the left ventromedial prefrontal cortex (vmPFC) may alter stress-induced executive dysfunction, emotion dysregulation, and drug-seeking in people with opioid use disorder. We will examine effects of a psychological stressor combined with inhibitory (1Hz) left vmPFC rTMS in participants (N=24) receiving opioid agonist treatment. Participants undergo guided imagery of autobiographical stressors paired with 10 sessions of active vmPFC rTMS vs. sham (within-subject randomized crossover). Stress-induced dysfunction will be indexed with cognitive (e.g., executive function), affective (e.g., emotional arousal), and behavioral (e.g., opioid-seeking) measures pre- and post-rTMS. To confirm changes are associated with altered neural activity in targeted regions, we will measure event-related potentials during key tasks using EEG. We hypothesize that stressors will increase executive dysfunction, emotion dysregulation, and drug-seeking, and that left vmPFC inhibitory rTMS will decrease limbic activation, which could translate to reduced craving and drug-seeking. Our findings should offer insights into how neural networks modulate drug-seeking and associated dysfunctions in people with SUDs. The results of this and similar studies can advance theory and neuromodulation interventions for people with SUDs.

Effects of non-invasive brain stimulation over the supplementary motor area on motor function in Parkinson's disease: A systematic review and meta-analysis.

Motor dysfunction profoundly affects individuals with Parkinson's disease (PD). Non-invasive brain stimulation (NIBS) targeting the supplementary motor area (SMA), a critical region for movement-related processing, offers a promising approach to enhance motor function for PD. This systematic review and meta-analysis aims to evaluate the efficacy of NIBS over the SMA (SMA-NIBS) in alleviating motor symptoms in PD. We conducted literature searches in MEDLINE, EMBASE, Physiotherapy Evidence Database, Web of Science, the Chinese National Knowledge Infrastructure, and Scopus. The meta-analysis utilized an inverse variance method and a random-effects model. Subgroup analyses were performed based on stimulation types (e.g., TMS and tDCS), stimulation protocols (e.g., facilitatory and inhibitory stimulation), and medication status during stimulation. Twenty randomized control trials involving 442 individuals with PD were included. Compared to sham stimulation, SMA-NIBS significantly improved motor function as measured by the motor section of Unified Parkinson's Disease Rating Scale (UPDRS-III) (mean differences [MD]: -3.45, 95% confidence interval [CI]: -5.65 to -1.26). Subgroup analysis revealed that only TMS (MD: -3.62, 95%CI: -6.15 to -1.08), not tDCS (MD: -2.47, 95% CI: -5.03 to 0.08), has significant effect on motor function. Both facilitatory (MD: -2.59, 95% CI: -3.37 to -1.82) and inhibitory stimulation (MD: -4.98, 95% CI: -9.29 to -0.66) significantly improved the UPDRS-III score. Effectiveness was observed only during ON medication. Statistically significant effects of SMA-NIBS were reported on Freezing of Gait Questionnaire, not timed up and go test and walking speed. SMA-NIBS is a promising approach to enhance motor function in PD.

Debunking the Myth of Excitatory and Inhibitory Repetitive Transcranial Magnetic Stimulation in Cognitive Neuroscience Research.

Repetitive TMS (rTMS) is a powerful neuroscientific tool with the potential to noninvasively identify brain-behavior relationships in humans. Early work suggested that certain rTMS protocols (e.g., continuous theta-burst stimulation, intermittent theta-burst stimulation, high-frequency rTMS, low-frequency rTMS) predictably alter the probability that cortical neurons will fire action potentials (i.e., change cortical excitability). However, despite significant methodological, conceptual, and technical advances in rTMS research over the past few decades, overgeneralization of early rTMS findings has led to a stubbornly persistent assumption that rTMS protocols by their nature induce behavioral and/or physiological inhibition or facilitation, even when they are applied to nonmotor cortical sites or under untested circumstances. In this Perspectives article, we offer a "public service announcement" that summarizes problems with these assumptions, highlighting limitations of seminal studies that inspired them and results of contemporary studies that violate them. Next, we discuss problems associated with holding these assumptions, including making brain-behavior inferences without confirming the locality and directionality of neurophysiological changes. Then, we emphasize results of recent studies showing that the effects of rTMS on neurophysiological metrics and their associated behaviors can be caused by mechanisms other than binary changes in excitability of the stimulated brain region or network. Finally, we provide recommendations for researchers to eliminate the misguided assumption that specific rTMS protocols are inherently excitatory or inhibitory when designing and interpreting their own work. Collectively, we contend that no rTMS protocol is by its nature either excitatory or inhibitory, and that researchers must use caution with these terms when forming experimental hypotheses and testing brain-behavior relationships.

From experimental phenomena to computational models: Exploring the synchronization mechanisms of phase-locked stimulation in the hippocampal–thalamic–cortical circuit for memory consolidation

Closed-loop phase-locking stimulation has been experimentally demonstrated to facilitate memory consolidation, which is believed to rely on the coordinated interactions among slow waves in multi-regional cortex, thalamocortical sleep spindles, and hippocampal ripples. However, the mechanisms through which this stimulation influences memory consolidation have not been thoroughly investigated. Therefore, starting from experimental phenomena, we computationally explored the synchronization mechanisms of memory consolidation in the hippocampal–thalamocortical (HTC) loop based on a firing rate model, and further reproduced the established effects of stimulation therapy on memory consolidation. The results indicate that excitatory connections between the cortex and hippocampus play a crucial role in the memory consolidation process. Additionally, our improved inhibitory closed-loop phase-locking stimulation protocol exhibits a more enhanced effect on memory consolidation compared to previous experimental stimulation schemes. Moreover, non-invasive stimulation shows lower side effects, costs, and implementation difficulties compared to invasive stimulation. Consequently, we further designed and explored the modulatory effects of a non-invasive magnetic–acoustic stimulation protocol. The results suggest that this non-invasive magnetic–acoustic stimulation yields effects comparable to those of existing invasive experimental deep brain stimulation. Our findings may provide new evidence and perspectives for understanding the neural mechanisms of memory processes and offer potential theoretical foundations for innovative non-invasive therapeutic strategies.

Transcranial electrical stimulation in post-traumatic stress disorder and brain injury: possibilities of tuning neuronal networks

Transcranial direct current stimulation (tDCS) in the treatment of post-traumatic stress disorder (PTSD) is used to strengthen the inhibitory control of amygdala activity. However, there are still limited meta-analytic studies examining different tDCS protocols on core PTSD symptoms and the relationship between stimulation parameters and effect size. The objective is to investigate the effectiveness of such an intervention, which is a complex combination of a psychotherapy program with tDCS in the treatment of patients with PTSD and mild traumatic brain injury (mTBI) by assessing their level of functioning. 329 veterans (PTSD (n=109), mTBI (n=112), PTSD + mTBI (n=108) were examined using WHODAS 2.0. Standardized treatment was provided as well as psy­chotherapeutic intervention - a combination of psychoeducation with motivational interviewing and acceptance and commitment therapy for PTSD and tDCS. Clinical targets of therapy in the PTSD group were symptoms of intrusion, avoidance, hyperactivation and protocol of tDCS was dorsolateral prefrontal cortex arousing stimulation. In PTSD + TBI group clinical targets were neurocognitive symptoms, intrusion symptoms, avoidance, hyperactivation and tDCT protocol was motor cortex-supraorbital area inhibitory stimulation. The targest for TBI group was neurocognitive symptoms and tDCS protocol was occipital region exciting stimulation. The long-term effectiveness and the impact on neuroplasticity processes allow considering transcranial direct current stimulation as a promising method of neurorehabilitation of patients with a combination of posttraumatic stress disorder and mild traumatic brain injury.

Efficacy of transcranial magnetic stimulation treatment in reducing neuropsychiatric symptomatology after traumatic brain injury.

Neuropsychiatric disorders are highly disabling in traumatic brain injury (TBI) patients, and psychopharmacological treatments often fail to adequately mitigate their detrimental effects. Repetitive transcranial magnetic stimulation (rTMS) is an emerging treatment in neurology and psychiatry, showing potential in treating psychiatric disorders. This study investigates the efficacy of a novel, dual-site sequential rTMS protocol designed to treat neuropsychiatric symptoms in a TBI patient who was refractory to conventional treatments. A 34-year-old woman with severe head trauma and complex psychopathology underwent 20 daily sessions of focal-coil rTMS, combining inhibitory stimulation (1 Hz) on the right dorsolateral prefrontal cortex (DLPFC) and excitatory (10 Hz) on the left DLPFC, guided by a neuronavigation system. Psychiatric and neurocognitive assessments were conducted at baseline and at 2, 4, and 8 weeks following the beginning of rTMS treatment. After 2 weeks of treatment, the patient showed decreased impulsivity and obsessive-compulsive symptoms, along with improvements in attention and processing speed. After 4 weeks, impulsivity further declined, though no other significant changes were noted. At 8 weeks, a persistent positive effect was observed, including enhanced positive emotions. These findings suggest that guided, alternating neurostimulation of the DLPFC may modulate activity within cortico-striato-thalamo-cortical circuits, providing a promising alternative for managing neuropsychiatric symptoms in TBI patients who are resistant to traditional treatments.

Investigating the effects of excitatory and inhibitory somatosensory rTMS on somatosensory functioning in the acute and subacute phases of stroke: a preliminary double-blind and randomized trial.

Repetitive transcranial magnetic stimulation (rTMS) targeting the primary somatosensory cortex (S1) has a potential effect on somatosensory functioning following a stroke. However, S1-rTMS was combined with peripheral therapies in previous trials. Moreover, these studies have commonly targeted the ipsilesional S1 with excitatory rTMS paradigms. This double-blind, randomized trial (registration number: ChiCTR2200059098) investigated two forms of paradigms, that is ipsilesional excitatory and contralesional inhibitory rTMS, as a stand-alone treatment in post-stroke somatosensation. Patients in the acute and subacute phases of stroke were randomly assigned to either contralesional 1-Hz or ipsilesional 10-Hz rTMS group and received 10 daily sessions of treatment in two consecutive weeks. Results indicate that the contralesional inhibitory and ipsilesional excitatory stimulation were equally effective in improving somatosensory functioning. Moreover, this effect was most prominent in deep sensations and subjective sensations. Using single-pulse EMG recordings, our data also revealed an increased MEP amplitude in the ipsilesional motor cortex following ipsilesional excitatory treatment. This preliminary study demonstrates the primary somatosensory cortex as an effective rTMS target in somatosensory recovery following stroke. https://www.chictr.org.cn/showproj.html?proj=166474, ChiCTR2200059098.

Speech perception following transcranial direct current stimulation (tDCS) over left superior temporal gyrus (STG) (including Wernicke's area) versus inferior frontal gyrus (IFG) (including Broca's area)

Imaging and neurocognitive studies have searched for the brain areas involved in speech perception, specifically when speech is accompanied by noise, attempting to identify the underlying neural mechanism(s). Transcranial direct current stimulation (tDCS), a noninvasive, painless cortical neuromodulation technique, has been used to either excite or inhibit brain activity in order to better understand the neural mechanism underlying speech perception in noise. In the present study, anodal (excitatory) and cathodal (inhibitory) stimulations were performed on 48 participants, either over the left Inferior Frontal Gyrus (IFG), which includes Broca's area (n = 10 anodal, and n = 10 cathodal) or over the left Superior Temporal Gyrus (STG), which includes Wernicke's area (n = 13 anodal, n = 15 cathodal). Speech perception was measured using a sentence recognition task accompanied by white noise with a signal-to-noise ratio of −10 dB. Speech perception performance was measured four times: at baseline, after each of the two sessions of stimulation (one active and one sham session, the order of which was randomized between participants), and at a two-week follow-up session. Groups receiving anodal and cathodal stimulation over the left IFG did not show an effect of stimulation type. For groups receiving left STG stimulation, anodal stimulation resulted in higher scores, regardless of whether it was given before or after sham stimulation. However, cathodal stimulation showed an effect only when active stimulation was applied following sham stimulation. These results showed that tDCS had a direct effect on improving speech perception only over left STG. Furthermore, while anodal stimulation was effective in whatever order it was given, cathodal stimulation was effective only following sham stimulation, thereby allowing some amount of training. These findings carry both theoretical and clinical implications for the relationship between the DMN's left IFG and left STG areas during speech perception accompanied by background noise.

Neuromodulation of the Right Motor Cortex of the Lips With Repetitive Transcranial Magnetic Stimulation to Reduce Phonological Impairment and Improve Naming in Three Persons With Aphasia: A Single-Case Experimental Design.

Repetitive transcranial magnetic stimulation (rTMS) can enhance aphasia recovery. Most studies have used inhibitory stimulation targeting the right inferior frontal gyrus. However, the motor cortex, observed to contribute to the prediction of aphasia recovery, is involved in word production and could be an appropriate target for rTMS. We aimed to observe behavioral changes in a picture naming task induced by inhibitory rTMS targeting the right motor cortex of the lips in people with poststroke aphasia. Using a single-case experimental design, we included three participants with chronic poststroke aphasia who had phonological deficits. Each participant performed a verbal picture naming task 3 times a week for 2, 3, or 4 weeks (pseudorandom across participants) to establish a baseline naming ability for each participant. These were not therapy sessions, and no feedback was provided. Then, each participant received the intervention, inhibitory continuous theta burst stimulation targeting the right motor cortex of the lips, 3 times a week for 2 weeks. Naming testing continued 3 times a week, for these latter 2 weeks. No therapy was performed at any time during the study. Visual analysis of the graphs showed a positive effect of rTMS for P2 and P3 on picture naming accuracy and a tendency toward improvement for P1. Statistical analysis showed an improvement after rTMS for P1 (τ = 0.544, p = .013, SETau = 0.288) and P2 (τ = 0.708, p = .001, SETau = 0.235). For P3, even if the intervention allowed some improvement, this was statistically nonsignificant due to a learning effect during the baseline naming testing, which lasted the longest, 4 weeks. Regarding specific language features, phonological errors significantly decreased in all patients. The motor cortex of the lips could be an appropriate target for rTMS to improve naming in people with poststroke aphasia suffering from a phonological deficit. This suggests the possibility to individualize the target for rTMS, according to the patient's linguistic impairment.

Continuous Theta-Burst Stimulation on the Left Posterior Inferior Frontal Gyrus Perturbs Complex Syntactic Processing Stability in Mandarin Chinese

Abstract The structure of human language is inherently hierarchical. The left posterior inferior frontal gyrus (LpIFG) is proposed to be a core region for constructing syntactic hierarchies. However, it remains unclear whether LpIFG plays a causal role in syntactic processing in Mandarin Chinese and whether its contribution depends on syntactic complexity, working memory, or both. We addressed these questions by applying inhibitory continuous theta-burst stimulation (cTBS) over LpIFG. Thirty-two participants processed sentences containing embedded relative clauses (i.e., complex syntactic processing), syntactically simpler coordinated sentences (i.e., simple syntactic processing), and non-hierarchical word lists (i.e., word list processing) after receiving real or sham cTBS. We found that cTBS significantly increased the coefficient of variation, a representative index of processing stability, in complex syntactic processing (esp., when subject relative clause was embedded) but not in the other two conditions. No significant changes in d′ and reaction time were detected in these conditions. The findings suggest that (a) inhibitory effect of cTBS on the LpIFG might be prominent in perturbing the complex syntactic processing stability but subtle in altering the processing quality; and (b) the causal role of the LpIFG seems to be specific for syntactic processing rather than working memory capacity, further evidencing their separability in LpIFG. Collectively, these results support the notion of the LpIFG as a core region for complex syntactic processing across languages.

Rehabilitation for Unilateral Spatial Neglect

Unilateral spatial neglect (USN) is a symptom of unilateral brain damage resulting in failure to report sensory phenomena in the contra-lesional space. It is associated with motor impairment as well as sensory deficits. Recent research suggests that USN, may be caused by a disruption in the interhemispheric balance of the visual attention network. Based on this hypothesis, non-invasive brain stimulation (NIBS), such as repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), is utilized in the rehabilitation of USN patients. Presently, inhibitory stimulation by continuous theta burst stimulation (cTBS) on contra-lesional parietal cortex are believed to be the most promising method. Conversely, compensation by attentional network of the non-lesioned hemisphere plays an important role in the recovery of USN. Recent imaging studies revealed that functional and structural connectivity of attentional networks within a lesioned hemisphere and between lesioned and non-lesioned hemispheres affects spontaneous recovery and effectiveness of rehabilitation approach such as prism adaptation therapy. These findings are useful in elucidating the pathophysiology of USN and predicting functional outcome. Furthermore, we hope that understanding the pathophysiology will enable the development of new rehabilitation strategies and appropriate treatment selection.

Information-based TMS to mid-lateral prefrontal cortex disrupts action goals during emotional processing

The ability to respond to emotional events in a context-sensitive and goal-oriented manner is essential for adaptive functioning. In models of behavioral and emotion regulation, the lateral prefrontal cortex (LPFC) is postulated to maintain goal-relevant representations that promote cognitive control, an idea rarely tested with causal inference. Here, we altered mid-LPFC function in healthy individuals using a putatively inhibitory brain stimulation protocol (continuous theta burst; cTBS), followed by fMRI scanning. Participants performed the Affective Go/No-Go task, which requires goal-oriented action during affective processing. We targeted mid-LPFC (vs. a Control site) based on the individualized location of action-goal representations observed during the task. cTBS to mid-LPFC reduced action-goal representations in mid-LPFC and impaired goal-oriented action, particularly during processing of negative emotional cues. During negative-cue processing, cTBS to mid-LPFC reduced functional coupling between mid-LPFC and nodes of the default mode network, including frontopolar cortex—a region thought to modulate LPFC control signals according to internal states. Collectively, these results indicate that mid-LPFC goal-relevant representations play a causal role in governing context-sensitive cognitive control during emotional processing.

Inferior parietal lobule stimulation in task-specific focal hand dystonia: A randomized, crossover clinical trial

Abstract OBJECTIVE: To determine the effect of inhibitory repetitive transcranial magnetic stimulation (rTMS) delivered to the left inferior parietal lobule (IPL) on the severity of task-specific focal hand dystonia. METHODS: In this randomized, sham-controlled, double-blind crossover study, participants received single sessions of low-frequency (1 Hz) inhibitory rTMS (1200 pulses) and sham stimulation to the left IPL. At baseline and after each session, we assessed the Writer’s Cramp Rating Scale (WCRS), kinematic analysis using an electrogoniometer, a torsiometer, and the patient-reported improvement on a Likert scale. RESULTS: We recruited 16 right-handed patients with task-specific focal hand dystonia [age: 33.3 ± 11.7 years, 13 male). The mean WCRS score at baseline was 5.8 ± 3.4 in group A (where first 1 Hz rTMS and then sham was applied) and 13.4 ± 5.2 in group B (where first sham and then 1 Hz rTMS were applied). An inhibitory rTMS protocol applied to the left IPL resulted in a statistically significant improvement in the WCRS total score [WCRS difference real minus sham mean (SD): −1 (1.3), (95% confidence interval (CI): −2, −1), p = 0.002] and writing movement score [WMS mean difference (SD): −1 (1.4), CI: (−2, 0), p = 0.005], irrespective of the sequence in which they received the intervention. Secondary outcomes were similar between the groups. CONCLUSION: In patients with task-specific focal hand dystonia, a single session of rTMS to the left IPL resulted in a modest reduction of focal hand dystonia severity. The results serve as a proof-of-concept for future studies to assess the clinical effects of multiple sessions of left IPL inhibition to modulate the abnormally hyperexcitable premotor–parietal–putaminal circuitry in task-specific focal hand dystonia.

Effects of pain on cortical homeostatic plasticity in humans: a systematic review.

Homeostatic plasticity (HP) is a negative feedback mechanism that prevents excessive facilitation or depression of cortical excitability (CE). Cortical HP responses in humans have been investigated by using 2 blocks of noninvasive brain stimulation with a no-stimulation block in between. A healthy HP response is characterized by reduced CE after 2 excitatory stimulation blocks and increased CE when using inhibitory stimulation. Conversely, impaired HP responses have been demonstrated in experimental and chronic pain conditions. Therefore, this systematic review aimed to provide an overview of the effect of pain on cortical HP in humans. Scopus, Embase, and PubMed were searched from inception until November 20, 2023. The included studies (1) compared experimental or clinical pain conditions with healthy controls, (2) induced HP using 2 blocks of stimulation with a no-stimulation interval, and (3) evaluated CE measures such as motor-evoked potentials. Four studies were included, consisting of 5 experiments and 146 participants, of whom 63 were patients with chronic pain and 48 were subjected to an experimental pain model. This systematic review found support for an HP impairment in pain compared with that in pain-free states, reflected by a lack of CE reduction after excitatory-excitatory HP induction over the primary motor cortex. Inhibitory-inhibitory HP induction did not produce a consistent HP response across studies, independent of pain or pain-free states. Standardization of HP induction protocols and outcome calculations is needed to ensure reproducibility and study comparison. Future HP studies may consider investigating sensory domains including nociception, which would further our understanding of abnormal HP regulation in pain conditions.

Causal role of the frontal eye field in attention-induced ocular dominance plasticity.

Previous research has found that prolonged eye-based attention can bias ocular dominance. If one eye long-termly views a regular movie meanwhile the opposite eye views a backward movie of the same episode, perceptual ocular dominance will shift towards the eye previously viewing the backward movie. Yet it remains unclear whether the role of eye-based attention in this phenomenon is causal or not. To address this issue, the present study relied on both the functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) techniques. We found robust activation of the frontal eye field (FEF) and intraparietal sulcus (IPS) when participants were watching the dichoptic movie while focusing their attention on the regular movie. Interestingly, we found a robust effect of attention-induced ocular dominance shift when the cortical function of vertex or IPS was transiently inhibited by continuous theta burst stimulation (cTBS), yet the effect was significantly attenuated to a negligible extent when cTBS was delivered to FEF. A control experiment verified that the attenuation of ocular dominance shift after inhibitory stimulation of FEF was not due to any impact of the cTBS on the binocular rivalry measurement of ocular dominance. These findings suggest that the fronto-parietal attentional network is involved in controlling eye-based attention in the 'dichoptic-backward-movie' adaptation paradigm, and in this network, FEF plays a crucial causal role in generating the attention-induced ocular dominance shift.

Causal role of the frontal eye field in attention-induced ocular dominance plasticity

Previous research has found that prolonged eye-based attention can bias ocular dominance. If one eye long-termly views a regular movie meanwhile the opposite eye views a backward movie of the same episode, perceptual ocular dominance will shift towards the eye previously viewing the backward movie. Yet it remains unclear whether the role of eye-based attention in this phenomenon is causal or not. To address this issue, the present study relied on both the functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) techniques. We found robust activation of the frontal eye field (FEF) and intraparietal sulcus (IPS) when participants were watching the dichoptic movie while focusing their attention on the regular movie. Interestingly, we found a robust effect of attention-induced ocular dominance shift when the cortical function of vertex or IPS was transiently inhibited by continuous theta burst stimulation (cTBS), yet the effect was significantly attenuated to a negligible extent when cTBS was delivered to FEF. A control experiment verified that the attenuation of ocular dominance shift after inhibitory stimulation of FEF was not due to any impact of the cTBS on the binocular rivalry measurement of ocular dominance. These findings suggest that the fronto-parietal attentional network is involved in controlling eye-based attention in the ‘dichoptic-backward-movie’ adaptation paradigm, and in this network, FEF plays a crucial causal role in generating the attention-induced ocular dominance shift.

Disentangling Cerebellar and Parietal Contributions to Gait and Body Schema: A Repetitive Transcranial Magnetic Stimulation Study

The overlap between motor and cognitive signs resulting from posterior parietal cortex (PPC) and cerebellar lesions can mask their relative contribution in the sensorimotor integration process. This study aimed to identify distinguishing motor and cognitive features to disentangle PPC and cerebellar involvement in two sensorimotor-related functions: gait and body schema representation. Thirty healthy volunteers were enrolled and randomly assigned to PPC or cerebellar stimulation. Sham stimulation and 1 Hz-repetitive-Transcranial-Magnetic-Stimulation were delivered over P3 or cerebellum before a balance and a walking distance estimation task. Each trial was repeated with eyes open (EO) and closed (EC). Eight inertial measurement units recorded spatiotemporal and kinematic variables of gait. Instability increased in both groups after real stimulation: PPC inhibition resulted in increased instability in EC conditions, as evidenced by increased ellipse area and range of movement in medio-lateral and anterior–posterior (ROMap) directions. Cerebellar inhibition affected both EC (increased ROMap) and EO stability (greater displacement of the center of mass). Inhibitory stimulation (EC vs. EO) affected also gait spatiotemporal variability, with a high variability of ankle and knee angles plus different patterns in the two groups (cerebellar vs parietal). Lastly, PPC group overestimates distances after real stimulation (EC condition) compared to the cerebellar group. Stability, gait variability, and distance estimation parameters may be useful clinical parameters to disentangle cerebellar and PPC sensorimotor integration deficits. Clinical differential diagnosis efficiency can benefit from this methodological approach.

Perceiving and misperceiving speech: lexical and sublexical processing in the superior temporal lobes.

Listeners can use prior knowledge to predict the content of noisy speech signals, enhancing perception. However, this process can also elicit misperceptions. For the first time, we employed a prime-probe paradigm and transcranial magnetic stimulation to investigate causal roles for the left and right posterior superior temporal gyri (pSTG) in the perception and misperception of degraded speech. Listeners were presented with spectrotemporally degraded probe sentences preceded by a clear prime. To produce misperceptions, we created partially mismatched pseudo-sentence probes via homophonic nonword transformations (e.g. The little girl was excited to lose her first tooth-Tha fittle girmn wam expited du roos har derst cooth). Compared to a control site (vertex), inhibitory stimulation of the left pSTG selectively disrupted priming of real but not pseudo-sentences. Conversely, inhibitory stimulation of the right pSTG enhanced priming of misperceptions with pseudo-sentences, but did not influence perception of real sentences. These results indicate qualitatively different causal roles for the left and right pSTG in perceiving degraded speech, supporting bilateral models that propose engagement of the right pSTG in sublexical processing.

Psychomotor Slowing in Psychosis and Inhibitory Repetitive Transcranial Magnetic Stimulation

Psychomotor slowing is a frequent symptom of psychosis, impairing gross and fine motor behavior. It is associated with poor outcomes and functioning, and no treatment is available. To investigate whether 15 sessions of inhibitory repetitive transcranial magnetic stimulation (rTMS) may reduce psychomotor slowing. This was a 4-arm, double-blind, randomized, sham-controlled trial at a university hospital in Switzerland. Enrollment took place from March 2019 to August 2022. Adults aged 18 to 60 years with schizophrenia spectrum disorders and severe psychomotor slowing were eligible. All patients continued existing medications, including antipsychotics and benzodiazepines. Those with substance misuse (other than nicotine), conditions associated with impaired or aberrant movement, convulsions, history of hearing problems, other conditions typically excluded from magnetic resonance imaging or TMS, any TMS treatment in the past 3 months, or those who were pregnant or breastfeeding were excluded. Of 615 patients screened for eligibility, 103 were randomized and 88 received at least 1 session of rTMS: 22 were assigned to 1-Hz rTMS, 22 to iTBS, 22 to sham, and 22 to the waiting group. Follow-up was conducted at 6 weeks and 24 weeks following the week 3 assessments including clinical, functional, and motor measures. Fifteen sessions of rTMS in 3 weeks over the supplementary motor area: 1-Hz rTMS, iTBS, sham, or no treatment (waiting). After 3 weeks, the waiting group received 15 sessions of 1-Hz rTMS over the supplementary motor area. The main outcome was the proportion of responders at week 3 in the Salpêtrière Retardation Rating Scale (SRRS) defined as a 30% or greater reduction from baseline (last-observation-carried-forward). The SRRS has 15 items and a maximum total score of 60. Of the 88 participants analyzed, 45 were men and 43 were women. The mean (SD) age was 36.3 (12.4) years and the mean (SD) SRRS score was 24.0 (5.9). A total of 69 participants completed the study. At week 3, response rates differed between groups: 15 of 22 (68%) in the 1-Hz rTMS group, 8 of 22 (36%) in the iTBS group, 7 of 22 (32%) in the sham group, and 4 of 22 (18%) in the waiting group (χ23 = 12.1; P = .007). The 1-Hz rTMS group had more responders than sham (odds ratio [OR], 0.13; 95% CI, 0.02-0.65; P = .03), iTBS (OR, 0.12; 95% CI, 0.02-0.61; P = .02), and waiting (OR, 0.04; 95% CI, 0.01-0.22; P = .003). In the waiting group, 10 of 16 participants (63%) responded after receiving 15 sessions of 1-Hz rTMS. No serious adverse events occurred. In this study, inhibitory add-on rTMS safely alleviated psychomotor slowing in psychosis compared with iTBS, sham, and no treatment. The treatment was also effective with delayed onset. Future studies need to explore the neural changes associated with supplementary motor area rTMS in psychosis. ClinicalTrials.gov Identifier: NCT03921450.

Real-time prediction of bladder urine leakage using fuzzy inference system and dual Kalman filtering in cats

The use of electrical stimulation devices to manage bladder incontinence relies on the application of continuous inhibitory stimulation. However, continuous stimulation can result in tissue fatigue and increased delivered charge. Here, we employ a real-time algorithm to provide a short-time prediction of urine leakage using the high-resolution power spectrum of the bladder pressure during the presence of non-voiding contractions (NVC) in normal and overactive bladder (OAB) cats. The proposed method is threshold-free and does not require pre-training. The analysis revealed that there is a significant difference between voiding contraction (VC) and NVC pressures as well as band powers (0.5–5 Hz) during both normal and OAB conditions. Also, most of the first leakage points occurred after the maximum VC pressure, while all of them were observed subsequent to the maximum VC spectral power. Kalman-Fuzzy method predicted urine leakage on average 2.2 s and 1.6 s before its occurrence and an average of 2.0 s and 1.1 s after the contraction started with success rates of 94.2% and 100% in normal and OAB cats, respectively. This work presents a promising approach for developing a neuroprosthesis device, with on-demand stimulation to control bladder incontinence.