While tactile perception has long been studied through the lens of discriminative touch, recent research has highlighted the existence of a distinct affective touch system. Pleasant touch refers to specific forms of light tactile stimulation, such as gentle stroking or caressing applied to hairy skin. This type of sensation is primarily conveyed by unmyelinated C-tactile (CT) afferents expressing a subclass of mechanoreceptors with low-threshold activation and slow-to-intermediate adaptation. Importantly, CT firing correlates strongly with subjective pleasantness ratings but not with intensity or localization accuracy, indicating a preferential role in affective rather than perceptual encoding. After reaching the superficial layers of the dorsal horn of the spinal cord, the projections ascend via pathways associated with interoception. Following thalamic relay, pleasant tactile information induces strong activation of a vast network including the posterior and anterior insula, the orbitofrontal cortex, the medial prefrontal cortex, the anterior cingulate cortex, and the ventral striatum. The literature converges on the idea that pleasant touch relies on a specialized neurophysiological system integrating peripheral CT afferents, insular processing, and neurochemical modulation, mainly involving oxytocin, dopamine, and opioid transmission. It impacts on autonomic nervous system regulation and physiological homeostasis, as shown by anti-stress effects of skin-to-skin contact in infants. Affective touch conveyed by CT afferents supports emotional regulation, social bonding, and well-being. In addition, pleasant touch has a therapeutic potential, especially in the pain domain, but also in other conditions dominated by negative thoughts, such as depressive disorders. Thus, the clinical utility of "affective touch therapy", even by means of robotic haptic stimulation, offers promising prospects for the treatment of anxiety-depressive or pain disorders, based on the neurophysiological effects of CT afferent activation.
This observational open-label study evaluates the clinical and neurophysiological effects of multiple sessions of contralesional motor cortex low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) on seventeen patients with chronic post-stroke hand spasticity. Results: LF-rTMS improved spasticity (Modified Ashworth Scale, p < 0.001), strength (tip pinch, p = 0.002; grip force, p < 0.001), flexibility (finger tapping test, p = 0.014; tapping test, p = 0.008), motor threshold difference (p < 0.001), and motor evoked potential latency (p = 0.004), with no adverse events reported. Improvement in spasticity persisted after 3 months. Conclusion: LF-rTMS is a safe and effective therapy for chronic post-stroke hand spasticity.
Breach rhythm (BR) is an EEG phenomenon typically associated with skull defects. While its continuous form is well recognized, the significance of intermittent BR has not been systematically studied. This cross-sectional, multicenter observational study included 90 patients with BR on routine EEGs. Patients were categorized based on BR continuity (continuous BR, CBR vs. intermittent BR, IBR). Structural imaging parameters, including residual lesion volume (RLV) and skull defect measurements, were also analyzed. Of 90 patients, 55 (61.1%) had CBR and 35 (38.9%) had IBR. There were no significant differences in demographic or seizure characteristics between groups. Residual lesion volumes were significantly larger in the CBR group, while skull defect size and surface area did not differ between groups. Interictal epileptiform discharges within BR regions were common in both groups (52.7% vs. 65.7%, p= 0.224). However, non-epileptiform interictal abnormalities outside BR regions were significantly more frequent in the IBR group (37.1% vs. 5.5%, p< 0.01). Right-sided BR was more often (70.2%) continuous than left-sided BR (48.8%) (p= 0.040). Breach rhythm on EEG can present as a continuous or intermittent pattern. Continuous BR appears associated with greater residual lesion burden and focal neurological findings, whereas intermittent BR is linked to smaller residual lesions but more widespread cortical abnormalities beyond the breach region. These findings suggest that BR reflects not only skull defects but also the functional state of underlying cortex. This study is the first to systematically differentiate intermittent from continuous BR, demonstrating that intermittent BR is common and BR may serve as a marker of distributed or dynamic cortical dysfunction in addition to structural cranial abnormalities.
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Aggressiveness is a complex social behavior that ranges from adaptive to pathological forms. This review synthesizes current knowledge of the neural circuits underlying aggression and explores how this informs neurosurgical strategies for severe, treatment-resistant cases. We reviewed recent experimental and clinical studies of the anatomical, functional, and neurochemical bases of aggression, focusing on reactive and proactive subtypes. Emphasis was placed on animal models, optogenetics, and human deep brain stimulation (DBS) approaches. Internal states - such as hormonal status, energy balance, and prior experience - modulate the threshold for aggression. The ventrolateral part of the ventromedial nucleus of the hypothalamus (VMHvl), particularly its ERα-expressing neurons, plays a central role in triggering aggressive behavior. The core aggression circuit (CAC) includes the VMHvl, amygdala, bed nucleus of the stria terminalis, and ventral premammillary nucleus, under modulation by prefrontal inputs. Aggression is expressed through a direct VMHvl-periaqueductal gray (PAG) pathway for innate actions and an indirect, dopamine-dependent striatal pathway for learned aggression. Serotonin inhibits, while dopamine promotes, proactive aggression. Pathological impulsive aggression, often linked to neurodevelopmental disorders and intellectual disability, may become refractory to pharmacotherapy. In such cases, neurosurgical approaches targeting the Sano triangle-originally described as part of the posterior hypothalamus-have shown promise. Understanding the connectivity and functional role of this region is essential for optimizing targeted interventions. Viewing aggression as a disorder of internal state regulation within defined circuits provides a framework for ethical and effective neuromodulation.
Severely brain-injured patients may enter a spectrum of conditions collectively known as disorders of consciousness. This spectrum includes clinical conditions such as unresponsive wakefulness syndrome or minimally conscious state, where the behavioural assessment of consciousness can often be deceptive. To bridge this dissociation, neuroimaging techniques are employed to identify the residual brain functions. Each neuroimaging modality imperfectly captures distinct aspects of brain preservation-functional, anatomical, or both. In this study, we adopt a comprehensive approach by integrating the neurophysiology and neuroimaging modalities available from the standard and advanced clinical assessments through interpretable machine learning. The electrophysiological modalities included high-density EEG (resting state and task), whereas neuroimaging modalities included anatomical and resting-state functional MRI, diffusion MRI and 18F-fluorodeoxyglucose PET. Our investigation reveals that specific modalities, such as functional assessments, provide comprehensive insights into the currently evaluated state of consciousness, the diagnosis of the patients. Conversely, structural modalities offer valuable information about the patient's evolution within the consciousness spectrum. We validate the proposed analysis with data coming from other centres with different acquisition parameters. Importantly, we demonstrate that model performance improves with an increase in the number of modalities. We observe a higher inter-modality disagreement for minimally conscious state patients and those patients who improve. Lastly, we observe a difference in feature importances between diagnosis and prognosis, with an interaction between modality and anatomical structures: some subcortical markers tend to contribute more to prognosis, while other cortical markers are more informative for diagnosis. This integrative multimodal and machine learning methodology presents a promising avenue for a more nuanced understanding of disorders of consciousness, contributing to enhanced diagnostic precision, prognostic capabilities and the personalization of rehabilitative strategies in clinical practice.
To assess the value of quantitative EEG (qEEG) as a diagnostic and prognostic biomarker in infants with abusive head trauma (AHT). Despite its central role in monitoring encephalopathy, EEG remains underused in multimodal evaluations, and its quantitative analysis may provide objective, real-time insights into cerebral dysfunction and long-term outcome. This retrospective monocentric case-control study included infants under two years with confirmed AHT and age- and sex-matched controls. Clinical and early EEG data were collected. Patients' outcome was stratified by Pediatric Overall Performance Category score (POPC1-3 vs. 4-6). Quantitative EEG features were analyzed, and two neural networks were trained using five-fold cross-validation for diagnosis and outcome prediction. 84 EEGs from 75 participants were analyzed (46 EEGs from 40 AHT; 38 EEGs from 35 controls). Compared with controls, AHT EEGs showed significantly reduced entropy and Hurst exponent values and increased low-frequency power, reflecting diffuse cortical dysfunction. Within the AHT group, reduced signal complexity and loss of interhemispheric asymmetry correlated with unfavorable outcomes (POPC4-6, p< 0.01). Machine learning perfectly classified AHT cases versus controls and classified patients into POPC1-3 or POPC4-6 groups with 73±14 % accuracy. Combined models distinguished control, POPC1-3, and POPC4-6 groups with 90±5 % accuracy. Early qEEG provides functional information that complements imaging and clinical findings. qEEG-derived biomarkers may enable early risk stratification, guide neuroprotective strategies, and improve prognostic counseling in infants with AHT. Larger multicenter prospective studies are warranted to validate these exploratory findings and define their clinical applicability.
To identify baseline predictors of clinical response to the primary motor cortex high-frequency repetitive transcranial magnetic stimulation (M1 HF-rTMS) in patients with fibromyalgia. We performed a secondary analysis of 32 women with fibromyalgia from a randomized, double-blind, sham-controlled international multicenter trial registered at clinicaltrials.gov (NCT03658694). Enrolled participants received active or HF-rTMS-over the primary motor cortex (M1). Baseline demographic data, psychological assessments (Hospital Anxiety and Depression Scale, Brief Pain Inventory, Fibromyalgia Impact Questionnaire, Toronto Alexithymia Scale, and Interoception Questionnaire), psychophysical measures (Conditioned Pain Modulation), and structural brain MRI variables were collected and analyzed. Responders were defined as patients who achieved a ≥ 50 % reduction in pain on a numerical rating scale eight weeks after treatment. Associations between baseline variables and response were analyzed using Wilcoxon Rank Sum tests, chi-square tests, and logistic regression where appropriate. At the end of the treatment period, 15 out of 32 participants (47 %) in the active M1 HF-rTMS group and 7 out of 30 (23 %) in the sham group achieved ≥50 % reduction in pain. None of the baseline demographic, clinical, psychological, psychophysical, or neuroimaging variables evaluated were significantly associated with clinical response to M1 HF-rTMS. Although M1 HF-rTMS induced significant antinociceptive effects measured by psychophysical assessments (heat pain threshold), these effects did not predict clinical outcomes. No clear baseline predictors of response to M1 HF-rTMS were identified in patients with fibromyalgia, emphasizing the heterogeneity and complexity of the disorder. Further research incorporating larger samples and additional biomarkers is necessary to establish individualized prediction strategies for M1 HF-rTMS therapy in fibromyalgia.
Amyotrophic lateral sclerosis (ALS) patients can exhibit split phenomena, with preferential weakness of specific muscle groups. The aim of this review is to investigate the split elbow (SE) phenomenon (different weakness/wasting pattern between biceps and triceps) as a potential clinical and neurophysiological feature in ALS. Our study was reported according to the PRISMA statement and registered in PROSPERO (CRD42024528359). MEDLINE, SCOPUS, Web of Science, and grey literature sources were searched using the terms "split elbow" and "amyotrophic lateral sclerosis" up to April 2025. English-written peer-reviewed, randomized, non-randomized, observational, diagnostic accuracy, and case-control studies were included. Study quality was assessed using Joanna Briggs Institute critical appraisal tool. Regarding muscle strength, we pooled the standardized mean difference of normalized Medical Research Council (MRC) scores using random effects. We used a bivariate random-effects model to evaluate SE index (SEICMAP, compound muscle action potential of biceps/triceps) in distinguishing ALS from controls. Seven studies with 1941 ALS patients (61.8 % male) met inclusion criteria. Pooled standardized mean difference (triceps - biceps MRC scores) was -0.17 [95 % CI, -1.03 to 0.69], p = 0.63, indicating no significant difference in muscle strength between elbow flexion and extension. Between-study heterogeneity was high (I2 = 97.1 % [95.5 %; 98.2 %], p < 0.0001). The SEICMAP demonstrated only moderate accuracy in distinguishing ALS from controls (pooled sensitivity, specificity, and AUC of 0.789 [0.655-0.880], 0.580 [0.487-0.668], and 0.661, respectively). Current evidence does not support a consistent SE pattern in ALS. Methodological variability and small sample sizes limit the generalizability of available findings, indicating that the SE is unlikely to provide meaningful diagnostic utility in routine clinical practice.
The hypersomnolence disorder diagnostic criteria of the DSM-5-TR rely on the report of a 'hypersomnolence' syndrome, without defining the term or proposing any measuring tool to assess this. Among the vast diversity of tools to measure hypersomnolence, the Hypersomnia Severity Index (HSI) has been specifically designed to account for the multidimensionality of hypersomnolence. Showing good psychometric validity in two previous validation studies, the HSI has never been validated against the gold-standard Multiple Sleep Latency Test (MSLT). This preliminary study aims to validate the French version of the HSI and to provide a first exploration of the link between HSI and the MSLT in a group of French subjects clinically diagnosed with hypersomnolence disorders. In addition, we propose an original visualization of the dimensions of the HSI. This study is a secondary analysis of a cohort of 34 patients diagnosed with hypersomnolence disorders without comorbidity. They underwent a MSLT and filled out the French version HSI as well as classical sleep medicine questionnaires. The HSI has undergone a rigorous translation and psychometric validation, which we compare with two previous psychometric validation studies. We obtained the same level of psychometric validity as previous studies, validating our French version on a population of patients with hypersomnolence disorder. However, we did not find any correlation between the HSI and the MSLT. Nevertheless, the dimensional approach offered by the HSI combined with our data visualization provide a valuable tool for sleep medicine clinical practice and research.
Recent findings suggest that key areas in the brain, particularly the medial prefrontal cortex (mPFC), are important for regulating bladder function. This research explores the potential of transcranial direct current stimulation (tDCS) on the mPFC as an emerging approach to alleviate overactive bladder (OAB) symptoms, in comparison to transcutaneous tibial nerve stimulation (TTNS). This single-blind, two-arm, parallel, randomized controlled clinical trial with a 1:1 allocation ratio was conducted at Firoozgar Hospital. A total of forty-four women diagnosed with overactive bladder (OAB) were randomly divided into two groups: one group received tDCS (transcranial Direct Current Stimulation) combined with PFMT (Pelvic Floor Muscle Training), and the other received TTNS(Trancutaneous Tibial Nerve Stimulation) combined with PFMT. The primary outcome measure was the quality of life through the International Consultation on Incontinence Questionnaire Lower Urinary Tract Symptoms Quality of Life Module (ICIQ-LUTSqol). Secondary outcome measures included the International Consultation on Incontinence Questionnaire Overactive Bladder Module (ICIQ-OAB), a three-day bladder diary, and assessment of pelvic floor muscle strength using a perineometer. Both groups exhibited improvements in OAB symptoms; however, the tDCS group appeared to show greater reductions in ICIQ-OAB scores and symptom bother (p < 0.05). As measured by the ICIQ-LUTSqol questionnaire, quality of life improved in both groups, with indications of comparatively greater improvements in the tDCS group after treatment and at the one-month follow-up (p = 0.05 and p < 0.05 respectively). Moreover, the number of urinary incontinence episodes tended to decline more markedly in the tDCS group, and this improvement was sustained during the follow-up period (p < 0.05). This study's findings suggest that while both TTNS and tDCS may effectively improve the quality of life in women with overactive bladder (OAB), the improvements observed in the tDCS group appear to be greater. However, further sham-controlled studies are needed to confirm these potential benefits. Iranian Registry of Clinical Trials (IRCT) ID: IRCT20090301001722N26, date of registration: 17 May 2023. https://en.irct.ir/.
Cortical electrical stimulation (CES) provides a unique window into the neural architecture supporting human emotion by perturbing local circuits while revealing distributed network dynamics. Yet despite decades of clinical use in stereo-EEG and subdural mapping, the emotional phenomena elicited by CES remain conceptually heterogeneous and methodologically inconsistent, reflecting the absence of a unified interpretative framework. Here, by outlining the conceptual foundations of emotion and examining the scattered evidence from CES, we show how definitional and methodological divergences undermine cumulative insight. We first situate CES findings relative to competing models of emotion, highlighting how assumptions about discreteness, appraisal, and construction shape the interpretation of evoked responses. We then assess how theoretical stance, emotion features, stimulation parameters, anatomical constraints, and task conditions are reported across studies, revealing major inconsistencies in methodological transparency than may account for systematic biases in affective outcomes. Finally, we propose the eMAP operational framework-a minimal reporting structure organised around four pillars: Emotion, Modulation, Architecture, and Phenomenology. This framework aims to guide future research by allowing perturbational evidence to be interpreted in a cumulative and comparable manner, while improving the clinical utility of CES for probing the functional architecture of emotion and refining surgical risk assessment.
The concept of cerebral localization originated from cerebral electrical stimulation. Pioneering experiments conducted by Fritsch and Hitzig on dogs, Bartholow on humans and David Ferrier on macaques in the 19th century led to the discovery of the primary motor cortex. Surgical treatment of epileptic patients began with electrical stimulation of the brain by Victor Horsley in 1886. Electrical stimulation of the brain during surgical treatment produced important results in terms of understanding of the cerebral cortex and focal epilepsies. In the 20th century, major developments were the electrocorticography work of Wilder Penfield in Montreal and the stereoelectroencephalography (SEEG) work of Jean Talairach and Jean Bancaud in Paris. The evolution of cerebral electrical stimulation reflects a growing understanding of brain organization and plasticity. This historical perspective highlights how empirical observations have shaped current clinical protocols and research frontiers.
In patients with functional neurological disorder (FND), transcranial magnetic stimulation (TMS) can be used for either diagnostic or therapeutic purpose. This study aimed to determine patients' expectations and tolerance of TMS techniques. Data were collected prospectively using a standardized questionnaire before, immediately after, and 14 days after a session combining TMS for diagnosis and treatment (based on repeated single-pulse TMS). 32 patients with FND were included. Most patients (79%) had received little or no information about TMS methods before the session. However, the majority of patients felt neither anxiety (78%) nor fear (69%) regarding this technique. With TMS, patients hoped more for a diagnosis (91%) than for even partial improvement of their symptoms (59%). Most patients (69%) rated the TMS experience as positive, although adverse events were frequent after the session (75%), but generally very mild. The occurrence of adverse events was associated with greater prior knowledge of TMS techniques and higher patients' expectations of treatment efficacy. Finally, an improvement in at least one of the initial symptoms was reported by 45% of patients during an interview conducted 14 days after the TMS session. This work fills a significant clinical gap in our understanding of the expectations of patients with FND regarding the applications of TMS, and their relationship to tolerance and short-term outcomes. Patients' initial knowledge of TMS did not alter their expectations, which were higher regarding its diagnostic than therapeutic value. An important finding of this study is that it demonstrates, for the first time, that the therapeutic efficacy of TMS is not related to patients' expectations or their initial level of information distinguishing this technique from a placebo.
Narcolepsy type 1 (NT1) is increasingly recognized as a multidimensional disorder in which psychiatric and psychosocial difficulties contribute to disability. Yet little is known about how these difficulties are perceived by patients compared with close informants. This study examined discrepancies between self-reported and informant-reported psychobehavioral symptoms in adults with NT1. Within the multicenter French NarcoScol-NarcoVitae cross-sectional case-control study, 174 adults with NT1 (18-58 years) and 126 age- and sex-matched non-relative controls completed the Adult Self-Report (ASR), a standardized measure of adult psychobehavioral problems. A close informant completed the parallel Adult Behavior Checklist (ABCL), yielding 97 NT1 and 96 control ASR-ABCL dyads. T-scores were computed for internalizing and externalizing scales, and the total problems score. Between-group differences (NT1 vs non-relative controls) and within-individual discrepancies between self- and informant-reported symptoms were analyzed. Narcolepsy severity (NSS), sleepiness (ESS), age at diagnosis, and a composite professional prognosis score were compared across concordant and discordant dyads. Patients with NT1 reported significantly higher psychiatric symptom severity than controls across all ASR scales, with 44.8% versus 19.1% in the clinical range for internalizing difficulties. Informants generally rated patients' symptom severity as lower than patients' self-reports, particularly for internalizing symptoms. Discordant dyads in which informants rated internalizing symptoms as more severe than patients were characterized by lower NT1 symptom burden (NSS). Concordant patient-informant evaluations were associated with a more favorable professional prognosis. Adults with NT1 report substantial psychobehavioral impairments that are not consistently identified by close informants, especially internalizing difficulties. This perception gap highlights the complementary value of patient and informant perspectives and calls for improved recognition of less visible symptoms within patients' close environment. NCT03765892.
Severe forms of generalised (GD) or cervical dystonia (CD) can be effectively treated with deep brain stimulation (DBS) of the globus pallidus interna (GPi). However, objectively assessing DBS effectiveness remains challenging. To identify objective biomarkers of GPi-DBS effectiveness using a minimalistic three-dimensional (3D) kinematic motion capture system in patients with dystonia. This retrospective longitudinal study analysed kinematic data from 14 patients before and after GPi-DBS: 7 with GD (3 females; mean age, 34.1±16.5 years; mean Burke-Fahn-Marsden (BFM) 32.9±14.1) and 7 with CD (4 females; mean age, 46.2±9.8 years; mean BFM 10.4±4.4). Parameters included barycentre displacement length, volume, velocity, angular velocity and power spectral density (PSD) in low-frequency (delta and theta) bands. Dystonia severity was assessed using the BFM scale. In the pooled cohort, GPi-DBS significantly reduced dystonia severity, with mean BFM scores decreasing from 21.6±15.4 preoperatively to 14.1±13.1 postoperatively (p=0.011, permutation test). In subgroup analyses, BFM scores decreased significantly in the CD group (p=0.015), while a non-significant trend toward improvement was observed in the GD group (p=0.076). Kinematic analysis in the pooled cohort demonstrated a robust reduction in barycentre angular velocity (p<0.001), whereas other parameters were not significantly modified. In the CD subgroup, additional significant reductions were observed in displacement length, velocity and PSD amplitudes in both frequency bands (all p<0.01). Multivariate regression analysis demonstrated that kinematic improvements in barycentre displacement length, velocity, angular velocity and PSD in delta and theta bands were significantly associated with clinical improvements (all p<0.05). 3D kinematic analysis provides objective biomarkers of GPi-DBS effectiveness in dystonia. Despite differing response patterns, kinematic features remain informative across phenotypes supporting their use in individualised outcome assessment.
Intracerebral electrical stimulation during stereoelectroencephalography (SEEG) is a key technique for functional mapping in the presurgical evaluation of patients with drug-resistant epilepsy. This article presents a concise anatomical overview and outlines standardized methodologies for SEEG-guided stimulation in motor, premotor, somatosensory, and operculo-insular regions. In these areas, functional stimulations are generally feasible under optimal conditions, yielding clear and reproducible clinical responses. We detail stimulation protocols, patient task paradigms, and the range of motor, sensory, and speech effects elicited, providing practical guidance for accurate and safe functional mapping in this eloquent cortex.
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To assess the diagnostic utility of distal sural (DSUR) sensory responses and amplitude ratios compared with conventional proximal sural (PSUR) studies in diabetic polyneuropathy (DPN). Fifty-eight patients with diabetes and clinical evidence of polyneuropathy (neuropathic symptoms and/or signs, median Neuropathy Impairment Score of the Lower Limbs (NIS-LL) score 6 [IQR 2-8]) and 44 healthy controls underwent bilateral nerve conduction studies of the PSUR and DSUR, and the right radial nerve. Amplitudes, conduction velocities (CV), and amplitude ratios [sural-to-radial amplitude ratio (SRAR), distal sural-to-radial amplitude ratio (DSRAR), and proximal-to-distal sural amplitude ratio (PDSR)] were analysed. PSUR and DSUR amplitudes were significantly lower and conduction velocities slower in patients compared with controls (p < 0.001). DSUR amplitude achieved diagnostic accuracy comparable to PSUR amplitude (AUC 0.762 vs. 0.775), with higher sensitivity (58.5% vs. 41.5 %) and preserved specificity (91 % vs. 93%). SRAR and DSRAR were reduced in patients, but their diagnostic performance was modest (AUC < 0.65). PDSR did not differ significantly between groups (p > 0.05) and was therefore not included in ROC analysis. Amplitude ratios showed weak correlations with diabetes duration, vibration threshold, and NIS-LL. DSUR amplitude is a feasible and reliable parameter that increases sensitivity in the electrophysiological detection of DPN while maintaining high specificity. In contrast, PDSR did not provide significant diagnostic value, suggesting that absolute amplitude measures are more informative than ratio-based indices in routine clinical practice.
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