Dopamine neuron degeneration in the Ventral Tegmental Area causes hippocampal hyperexcitability in experimental Alzheimer's Disease.

Early and progressive dysfunctions of the dopaminergic system from the Ventral Tegmental Area (VTA) have been described in Alzheimer's Disease (AD). During the long pre-symptomatic phase, alterations in the function of Parvalbumin interneurons (PV-INs) are also observed, resulting in cortical hyperexcitability represented by subclinical epilepsy and aberrant gamma-oscillations. However, it is unknown whether the dopaminergic deficits contribute to brain hyperexcitability in AD. Here, using the Tg2576 mouse model of AD, we prove that reduced hippocampal dopaminergic innervation, due to VTA dopamine neuron degeneration, impairs PV-IN firing and gamma-waves, weakens the inhibition of pyramidal neurons and induces hippocampal hyperexcitability via lower D2-receptor-mediated activation of the CREB-pathway. These alterations coincide with reduced PV-IN numbers and Perineuronal Net density. Importantly, L-DOPA and the selective D2-receptor agonist quinpirole rescue p-CREB levels and improve the PV-IN-mediated inhibition, thus reducing hyperexcitability. Moreover, similarly to quinpirole, sumanirole - another D2-receptor agonist and a known anticonvulsant - not only increases p-CREB levels in PV-INs but also restores gamma-oscillations in Tg2576 mice. Conversely, blocking the dopaminergic transmission with sulpiride (a D2-like receptor antagonist) in WT mice reduces p-CREB levels in PV-INs, mimicking what occurs in Tg2576. Overall, these findings support the hypothesis that the VTA dopaminergic system integrity plays a key role in hippocampal PV-IN function and survival, disclosing a relevant contribution of the reduced dopaminergic tone to aberrant gamma-waves, hippocampal hyperexcitability and epileptiform activity in early AD.

High-frequency transcranial alternating current stimulation matching individual frequency of somatosensory evoked high-frequency oscillations can modulate the somatosensory system through thalamocortical pathway.

tACS (transcranial alternating current stimulation) is a technique for modulating brain activity through electrical current. Its effects depend on cortical entrainment, which is most effective when transcranial alternating current stimulation matches the brain's natural rhythm. High-frequency oscillations produced by external stimuli are useful for studying the somatosensory pathway. Our study aims to explore transcranial alternating current stimulation's impact on the somatosensory system when synchronized with individual high-frequency oscillation frequencies. We conducted a randomized, sham-controlled study with 14 healthy participants. The study had three phases: Individualized transcranial alternating current stimulation (matching the individual's high-frequency oscillation rhythm), Standard transcranial alternating current stimulation (600 Hz), and sham stimulation. We measured early and late HFO components after median nerve electrical stimulation at three time points: before (T0), immediately after (T1), and 10 min after transcranial alternating current stimulation (T2). Compared to Sham and Standard stimulation Individualized transcranial alternating current stimulation significantly enhanced high-frequency oscillations, especially the early component, immediately after stimulation and for at least 15 min. No other effects were observed for other high-frequency oscillation measures. In summary, our study provides initial evidence that transcranial alternating current stimulation synchronized with an individual's high-frequency oscillation frequency can precisely and time-specifically modulate thalamocortical activity. These insights may pave the way for innovative, personalized neuromodulation methods for the somatosensory system.

Cortical plasticity in AQP4-positive NMOSD: a transcranial magnetic stimulation study.

Aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD) is an autoimmune disease characterized by suboptimal recovery from attacks and long-term disability. Experimental data suggest that AQP4 antibodies can disrupt neuroplasticity, a fundamental driver of brain recovery. A well-established method to assess brain LTP is through intermittent theta-burst stimulation (iTBS). This study aimed to explore neuroplasticity in AQP4-NMOSD patients by examining long-term potentiation (LTP) through iTBS. We conducted a proof-of-principle study including 8 patients with AQP4-NMOSD, 8 patients with multiple sclerosis (MS), and 8 healthy controls (HC) in which iTBS was administered to induce LTP-like effects. iTBS-induced LTP exhibited significant differences among the 3 groups (p: 0.006). Notably, AQP4-NMOSD patients demonstrated impaired plasticity compared to both HC (p = 0.01) and pwMS (p = 0.02). This pilot study provides the first in vivo evidence supporting impaired neuroplasticity in AQP4-NMOSD patients. Impaired cortical plasticity may hinder recovery following attacks suggesting a need for targeted rehabilitation strategies.

Incidence and determinants of seizures in multiple sclerosis: a meta-analysis of randomised clinical trials.

BACKGROUND: Seizures are reported to be more prevalent in individuals with multiple sclerosis (MS) compared with the general population. Existing data predominantly originate from population-based studies, which introduce variability in methodologies and are vulnerable to selection and reporting biases. METHODS: This meta-analysis aims to assess the incidence of seizures in patients participating in randomised clinical trials and to identify potential contributing factors. Data were extracted from 60 articles published from 1993 to 2022. The pooled effect size, representing the incidence rate of seizure events, was estimated using a random-effect model. Metaregression was employed to explore factors influencing the pooled effect size. RESULTS: The meta-analysis included data from 53 535 patients and 120 seizure events in a median follow-up of 2 years. The pooled incidence rate of seizures was 68.0 per 100 000 patient-years, significantly higher than the general population rate of 34.6. Generalised tonic-clonic seizures were the most common type reported, although there was a high risk of misclassification for focal seizures with secondary generalisation. Disease progression, longer disease duration, higher disability levels and lower brain volume were associated with a higher incidence of seizures. Particularly, sphingosine-1-phosphate receptor (S1PR) modulators exhibited a 2.45-fold increased risk of seizures compared with placebo or comparators, with a risk difference of 20.5 events per 100 000 patient-years. CONCLUSIONS: Patients with MS face a nearly twofold higher seizure risk compared with the general population. This risk appears to be associated not only with disease burden but also with S1PR modulators. Our findings underscore epilepsy as a significant comorbidity in MS and emphasise the necessity for further research into its triggers, preventive measures and treatment strategies.

Left Vagus Stimulation Modulates Contralateral Subthalamic ß Power Improving the Gait in Parkinson's Disease.

BACKGROUND: Transcutaneous vagus nerve stimulation (VNS) showed early evidence of efficacy for the gait treatment of Parkinson's disease (PD). OBJECTIVES: Providing data on neurophysiological and clinical effects of transauricular VNS (taVNS). METHODS: Ten patients with recording deep brain stimulation (DBS) have been enrolled in a within participant design pilot study, double-blind crossover sham-controlled trial of taVNS. Subthalamic local field potentials (ß band power), Unified Parkinson's Disease Rating Scales (UPDRS), and a digital timed-up-and-go test (TUG) were measured and compared with real versus sham taVNS during medication-off/DBS-OFF condition. RESULTS: The left taVNS induced a reduction of the total ß power in the contralateral (ie, right) subthalamic nucleus and an improvement of TUG time, speed, and variability. The taVNS-induced ß reduction correlated with the improvement of gait speed. No major clinical changes were observed at UPDRS. CONCLUSIONS: taVNS is a promising strategy for the management of PD gait, deserving prospective trials of chronic neuromodulation. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

A new gene for autosomal dominant facial palsy/migraine identified in a family by whole exome sequencing.

BACKGROUND: Facial palsy manifests as unilateral or bilateral weakness and inability to move some of the facial muscles. The aetiology may be different including idiopathic, trauma, infections or brain tumours or it can be associated with chronic neurological diseases. For instance, in recurrent migraine, an increased risk of idiopathic facial palsy (often unilateral) has been observed. Migraine is a neurovascular disorder characterized by mild to severe intensity of headaches, often associated with neuro-ophthalmological symptoms. METHODS: A family is reported where five members were affected by facial palsy associated with other clinical features including migraine, diplopia, facial swelling, eye conjunctivitis following a vertical transmission. Whole exome sequencing was performed in three members (two affected and one healthy) in order to identify potential variants causative of their phenotype. RESULTS: A missense variant c.304G>A was found leading to the p.(Ala102Thr) substitution in the TRPM8 gene, previously related to migraine by genome wide association studies. This variant was classified as deleterious by several predictor tools, and the mutant residue was predicted to alter the protein structure in terms of flexibility and interactions with the surrounding residues. CONCLUSION: These findings suggest that TRPM8 could be a new causative gene further linking migraine and recurrent facial palsy.

Restless leg syndrome as a complication of primary hyperparathyroidism: insights from a retrospective study.

INTRODUCTION: Restless leg syndrome (RLS) is an invalidating neurological disorder with a complex, largely unknown pathophysiology. While RLS is observed in Parkinson's disease and in renal failure, idiopathic cases are common. Limited reports associate RLS with parathyroid hormone (PTH). This study analyzes a cohort of patients with primary hyperparathyroidism (PHPT) and chronic post-surgical hypoparathyroidism (hypo PTH), to investigate RLS prevalence, and associated risk factors. METHODS: Ninety-five patients (54 PHPT, 41 hypo PTH) were consecutively enrolled at the bone metabolism outpatient clinic. The revised IRLSSG diagnostic criteria were used to diagnose RLS, with assessments conducted through face-to-face interviews and neurological examination. When RLS was confirmed, the RLS severity scale was applied. Retrospective records included calcium-phosphate metabolism-related parameters, surgery details, renal lithiasis, fragility fractures, and densitometric features (T-score). RESULTS: RLS was diagnosed in 22.2% PHPT patients, compared to 4.9% of patients with hypo PTH (p = 0.02). Of RLS diagnosed patients, 91.7% had a history of parathyroidectomy, compared to 47.6% of patients without RLS (p = 0.01). Most of the operated patients reported that surgery determined an improvement of symptoms; however, mean score severity of RLS at our evaluation was 15/40, defined as moderate. PTH and calcium levels were not statistically associated to the presence of RLS. CONCLUSION: Our study suggests that PHPT may be one of the etiologies of RLS. Parathyroidectomy alleviates symptoms in the vast majority of the cases but does not remove them.

Emotional atypical arousal ratings for unpleasant stimuli in patients with Parkinson's disease.

INTRODUCTION: Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor and non-motor symptoms, including alteration in emotional processing and recognition of emotions. We explored the effects of PD on the emotional behavioral ratings using a battery of affective visual stimuli selected from the International Affective Picture System (IAPS). METHODS: Twenty-two patients diagnosed with idiopathic PD and 22 healthy controls (HC), matched by age, gender, and education, were enrolled in the study. Following a clinical assessment, each participant was asked to evaluate the arousal and valence of affective visual stimuli, and response time was recorded. Disease-specific measures including the MDS Unified Parkinson's Disease Rating Scale (MDS UPDRS) and the Non-Motor Symptom Scale (NMSS) were also collected. RESULTS: PD patients exhibited higher arousal responses compared to HC for negative/unpleasant pictures (scoring 7.32 ± 0.88 vs 5.43 ± 2.06, p < 0.001). The arousal response to negative/unpleasant pictures was correlated with measures of non-motor burden in PD (MDS UPDRS I and NMSS, rho = 0.480 and p = 0.023, rho = 0.533 and p = 0.010, respectively). CONCLUSION: Impaired emotional processing characterizes PD patients with mild disease and is related to the non-motor symptom burden. Given the importance of emotional processing for the development and maintenance of close interpersonal relationship and for coping with specific medical situations, it is crucial to direct PD patients towards therapeutic interventions focused on the recognition and processing of emotions.

Unusual CLIPPERS presentation with a predominant spinal cord involvement: case report and review of the literature.

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a discrete nosological entity characterized by punctate and curvilinear gadolinium enhancement "peppering" the pons and a strong response to steroids. MRI images typically show pontine and cerebellar punctate-enhancing lesions, which occasionally spread up to the juxtacortical areas and down to the spinal cord. Interestingly, the more distant the lesion is from the pons, the less intense they become. Herein, we describe an extremely rare case of CLIPPERS presenting with predominant spinal cord involvement; then, we searched in the literature the available cases with a similar presentation. Our case focuses attention on a rare MRI CLIPPERS presentation. Since CLIPPERS has a dramatic response to corticosteroid treatment, it is fundamental to promptly recognize its MRI pattern to start treatment as soon as possible.

Overnight switch from carbamazepine to eslicarbazepine in a real-life clinical scenario: a retrospective study.

BACKGROUND: Carbamazepine (CBZ) is a first-choice anti-seizure medication (ASM) whose efficacy is often invalidated by adverse effects (AEs). Eslicarbazepine (ESL) is a structural derivative of CBZ with better pharmacokinetic/tolerability profiles. We describe our experience of the overnight CBZ to ESL switch in people with epilepsy (PwE) to improve seizure control, AEs, and ASMs adherence. METHODS: We retrospectively included 19 PwE (12 females, 53 ± 21 years old) who underwent CBZ to ESL overnight switch due to single/multiple issues: poor efficacy (pEff, N = 8, 42%), tolerability (pToll, N = 11, 58%), adherence (pAdh, N = 2, 10%). 9/19 (47%) had psychiatric comorbidities. Clinical variables, seizure frequency, and AEs were recorded at switch time (T0) after 3.5 ± 3 (T1) and 6.5 ± 1.5 months (T2). RESULTS: At T1, in pEff group, 1/8 (13%) was seizure free, 2/8 (25%) were responders (> 50% seizure reduction), 2/8 (25%) had no seizure changes, 3/8 (37%) had seizure worsening; the latter were those with the most severe epilepsy and encephalopathy. In pToll group, all PwE experienced AEs disappearance/amelioration. In pAdh group, all PwE reported adherence amelioration. Four dropouts. At T2, no changes were recorded within groups, while in the whole sample, 6/15 (40%) were responders, and 4/15 (27%) were seizure-free. No one complained of Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation psychiatric worsening, while 6/19 (32%) experienced mood/behavior benefits. CONCLUSIONS: CBZ to ESL overnight switch offers an opportunity to improve efficacy, tolerability, adherence, and psychiatric symptoms.

Body image appearance in Parkinson's disease patients on device aided therapies.

INTRODUCTION: Parkinson's disease patients may experience altered body image perception. Advanced Parkinson's disease (aPD) with motor complications often requires surgical and device-aided treatments (DAT), such as levodopa-carbidopa intestinal gel (LCIG) and deep brain stimulation (DBS). Understanding body image perception is crucial when managing these devices. This study aims to explore body image perception in aPD patients, hypothesizing a link between DAT and body image perception. METHODS: We performed a cross-sectional study including non-demented aPD patients with and without DAT and age- and sex-matched controls. Participants were assessed using the Appearance Schemas Inventory-Revised (ASI-R), including Motivational Salience (MS) and Self-Evaluative Salience (SES) scores. Additional data included age, education, BMI, comorbidities, pharmacotherapy, and psychopathologies. PD patients were also evaluated with UPDRS, Hoehn and Yahr scales and LEDD calculation. RESULTS: 70 aPD and 36 controls were enrolled. No differences in ASI-R scores were found between PD patients and controls, but women with PD had significantly lower MS scores than controls (16.1 ± 5.6 vs 19.7 ± 5.8; p = 0.023). Among aPD patients, those on DAT had longer disease duration, higher Hoehn and Yahr, and lower UPDRS IV scores. The lowest MS was observed in women on LCIG (12.7 ± 3.3; p = 0.001). DISCUSSION: This study shows low MS ratings driven by female gender and LCIG treatment. Women on LCIG show reduced attention and management of their appearance. This may be influenced by cultural, environmental, and biological factors. Prospective research is needed to understand the impact of DAT on body image.

Exploring vertebral artery stump syndrome: An overlooked cause of posterior ischemic strokes. A narrative review of current management options.

INTRODUCTION: Stump syndrome is defined as a clinical syndrome resulting from a distal intracranial vessel embolic stroke due to an extracranial vessel occlusion. Similar to the anterior circulation, the recurrence of ischemic strokes in territories supplied by the posterior circulation in the presence of vertebral artery occlusion is termed Vertebral Artery Stump Syndrome (VASS). MATERIAL AND METHODS: We conducted a literature review, identifying 72 patients with transient ischemic attacks (TIAs) or ischemic strokes attributed to VASS, according to Kawano criteria. We categorized all patients in two groups focusing on the therapeutic management those who underwent primary medical treatment and those who received endovascular or surgical treatment either in acute or chronic phase. RESULTS: In the anticoagulant therapy group, only 1 patient had a stroke recurrence. Among the 4 on antiplatelets, all had recurrences, but 3 benefited from switching to anticoagulants or endovascular therapy. In the endovascular therapy group, worse outcomes were linked to acute large vessel occlusion. Endovascular treatment of the vertebral artery, in a chronic phase, was explored in literature for recurrent TIAs or minor strokes suggesting that this could be a viable therapeutic alternative when medical treatment failed in preventing recurrence of ischemic stroke. CONCLUSIONS: Some studies suggest that anticoagulant medical therapy may be beneficial for VASS and endovascular therapy has also been reported for selected patients. However, data on treatment outcomes and prognosis are still underreported, making treatment decisions challenging. Randomized Controlled Trials are needed to establish the optimal treatment approach.

Evaluating the effect of calcifediol supplementation on seizure frequency in people with drug-resistant epilepsy.

The well-known neuroprotective role and involvement of vitamin D in the function of the central nervous system has raised the speculation about the possible antiseizure effect of vitamin D supplementation. This issue is crucial when considering people with epilepsy (PWE), who frequently display vitamin D deficiency, but nowadays data are still unconclusive. In our study, we enrolled 25 adult patients affected by drug-resistant epilepsy and hypovitaminosis D to test the effect of Calcifediol on seizure frequency after 6 months of supplementation. Our findings evidenced that Calcifediol administration completely restored 25-hydroxy vitamin D (25-OHD) and intact parathyroid hormone (iPTH) serum values (p < 0.001 for both) without significant changes of median seizure frequency (-6.1%). Anyway, we observed some rate of PWE responders (32%) to Calcifediol supplementation. Further randomized controlled trials with larger subjects 'samples will be needed to verify the possible antiseizure effect of vitamin D.

Deep brain stimulation of the dentato-rubro-thalamic tract in a case of Holmes tremor: a constrained spherical deconvolution (CSD)-guided procedure.

Deep brain stimulation (DBS) is an established treatment for movement disorders, including Holmes tremor (HT). HT is a rest and action tremor that occurs as a late symptom of brainstem lesions such as stroke. Unfortunately, it is frequently refractory to medical treatment, hence DBS surgery may be a good option. Due to variable results, the ideal target for DBS in HT still remains to be established, ranging from the thalamus to the globus pallidus internus, to the subthalamic nucleus. Pre-operative imaging also is very challenging, as the complexity of brain fiber architecture may prevent the correct positioning of the directional lead. Herein, we describe the case of a patient affected by a rubral tremor secondary to a brain hemorrhage, who had advanced pre-operative neuroimaging with constrained spherical deconvolution (CSD)-based tractography obtained from diffusion-weighted imaging (DWI) to identify the dentato-rubro-thalamic tract, involved in the pathophysiology of HT. The patient was then addressed to an awake DBS surgery, and with the help of intraoperative microelectrode recordings, a tailored DRTT-targeted procedure was performed. The stimulation determined an almost complete tremor suppression, with no significant side effects at a follow-up of 6 months, paving the way towards new effective techniques for the planning, i.e., CSD-based tractography and the treatment of refractory tremors.

A true isolated cognitive relapse in multiple sclerosis.

Isolated cognitive relapses (ICRs) have been a matter of debate for the past few years. Currently, there is no clear consensus on such an entity, as cognitive decline usually accompanies typical multiple sclerosis (MS) relapses. Herein, we present the neuropsychological and neurophysiological manifestations of a patient who suddenly complained of confusion and memory loss, showing insight into her deficit, in absence of sensorimotor disturbances. Neuroimaging revealed a large tumefactive gadolinium-enhancing lesion localized in the left medial temporal lobe. The patient's symptoms persisted for months afterwards, despite corticosteroid treatment. We believe our patient experienced a true ICR. ICRs are rare entities in MS, but we should be alert to their existence in order to treat them promptly. Deepening their pathophysiology is equally important and neuropsychology combined with neurophysiology may be useful in this regard.

Integration of proprioception in upper limb prostheses through non-invasive strategies: a review.

Proprioception plays a key role in moving our body dexterously and effortlessly. Nevertheless, the majority of investigations evaluating the benefits of providing supplemental feedback to prosthetics users focus on delivering touch restitution. These studies evaluate the influence of touch sensation in an attempt to improve the controllability of current robotic devices. Contrarily, investigations evaluating the capabilities of proprioceptive supplemental feedback have yet to be comprehensively analyzed to the same extent, marking a major gap in knowledge within the current research climate. The non-invasive strategies employed so far to restitute proprioception are reviewed in this work. In the absence of a clearly superior strategy, approaches employing vibrotactile, electrotactile and skin-stretch stimulation achieved better and more consistent results, considering both kinesthetic and grip force information, compared with other strategies or any incidental feedback. Although emulating the richness of the physiological sensory return through artificial feedback is the primary hurdle, measuring its effects to eventually support the integration of cumbersome and energy intensive hardware into commercial prosthetic devices could represent an even greater challenge. Thus, we analyze the strengths and limitations of previous studies and discuss the possible benefits of coupling objective measures, like neurophysiological parameters, as well as measures of prosthesis embodiment and cognitive load with behavioral measures of performance. Such insights aim to provide additional and collateral outcomes to be considered in the experimental design of future investigations of proprioception restitution that could, in the end, allow researchers to gain a more detailed understanding of possibly similar behavioral results and, thus, support one strategy over another.

Intraoperative Local Field Potential Beta Power and Three-Dimensional Neuroimaging Mapping Predict Long-Term Clinical Response to Deep Brain Stimulation in Parkinson Disease: A Retrospective Study.

BACKGROUND: Directional deep brain stimulation (DBS) leads allow a fine-tuning control of the stimulation field, however, this new technology could increase the DBS programming time because of the higher number of the possible combinations used in directional DBS than in standard nondirectional electrodes. Neuroimaging leads localization techniques and local field potentials (LFPs) recorded from DBS electrodes implanted in basal ganglia are among the most studied biomarkers for DBS programing. OBJECTIVE: This study aimed to evaluate whether intraoperative LFPs beta power and neuroimaging reconstructions correlate with contact selection in clinical programming of DBS in patients with Parkinson disease (PD). MATERIALS AND METHODS: In this retrospective study, routine intraoperative LFPs recorded from all contacts in the subthalamic nucleus (STN) of 14 patients with PD were analyzed to calculate the beta band power for each contact. Neuroimaging reconstruction obtained through Brainlab Elements Planning software detected contacts localized within the STN. Clinical DBS programming contact scheme data were collected after one year from the implant. Statistical analysis evaluated the diagnostic performance of LFPs beta band power and neuroimaging data for identification of the contacts selected with clinical programming. We evaluated whether the most effective contacts identified based on the clinical response after one year from implant were also those with the highest level of beta activity and localized within the STN in neuroimaging reconstruction. RESULTS: LFPs beta power showed a sensitivity of 67%, a negative predictive value (NPV) of 84%, a diagnostic odds ratio (DOR) of 2.7 in predicting the most effective contacts as evaluated through the clinical response. Neuroimaging reconstructions showed a sensitivity of 62%, a NPV of 77%, a DOR of 1.20 for contact effectivity prediction. The combined use of the two methods showed a sensitivity of 87%, a NPV of 87%, a DOR of 2.7 for predicting the clinically more effective contacts. CONCLUSIONS: The combined use of LFPs beta power and neuroimaging localization and segmentations predict which are the most effective contacts as selected on the basis of clinical programming after one year from implant of DBS. The use of predictors in contact selection could guide clinical programming and reduce time needed for it.

Unlocking the Potential of Stroke Blood Biomarkers: Early Diagnosis, Ischemic vs. Haemorrhagic Differentiation and Haemorrhagic Transformation Risk: A Comprehensive Review.

Stroke, a complex and heterogeneous disease, is a leading cause of morbidity and mortality worldwide. The timely therapeutic intervention significantly impacts patient outcomes, but early stroke diagnosis is challenging due to the lack of specific diagnostic biomarkers. This review critically examines the literature for potential biomarkers that may aid in early diagnosis, differentiation between ischemic and hemorrhagic stroke, and prediction of hemorrhagic transformation in ischemic stroke. After a thorough analysis, four promising biomarkers were identified: Antithrombin III (ATIII), fibrinogen, and ischemia-modified albumin (IMA) for diagnostic purposes; glial fibrillary acidic protein (GFAP), micro RNA 124-3p, and a panel of 11 metabolites for distinguishing between ischemic and hemorrhagic stroke; and matrix metalloproteinase-9 (MMP-9), s100b, and interleukin 33 for predicting hemorrhagic transformation. We propose a biomarker panel integrating these markers, each reflecting different pathophysiological stages of stroke, that could significantly improve stroke patients' early detection and treatment. Despite promising results, further research and validation are needed to demonstrate the clinical utility of this proposed panel for routine stroke treatment.

Sensorimotor integration within the primary motor cortex by selective nerve fascicle stimulation.

The integration of sensory inputs in the motor cortex is crucial for dexterous movement. We recently demonstrated that a closed-loop control based on the feedback provided through intraneural multichannel electrodes implanted in the median and ulnar nerves of a participant with upper limb amputation improved manipulation skills and increased prosthesis embodiment. Here we assessed, in the same participant, whether and how selective intraneural sensory stimulation also elicits a measurable cortical activation and affects sensorimotor cortical circuits. After estimating the activation of the primary somatosensory cortex evoked by intraneural stimulation, sensorimotor integration was investigated by testing the inhibition of primary motor cortex (M1) output to transcranial magnetic stimulation, after both intraneural and perineural stimulation. Selective sensory intraneural stimulation evoked a low-amplitude, 16 ms-latency, parietal response in the same area of the earliest component evoked by whole-nerve stimulation, compatible with fast-conducting afferent fibre activation. For the first time, we show that the same intraneural stimulation was also capable of decreasing M1 output, at the same time range of the short-latency afferent inhibition effect of whole-nerve superficial stimulation. The inhibition generated by the stimulation of channels activating only sensory fibres was stronger than that due to intraneural or perineural stimulation of channels activating mixed fibres. We demonstrate in a human subject that the cortical sensorimotor integration inhibiting M1 output previously described after the experimental whole-nerve stimulation is present also with a more ecological selective sensory fibre stimulation. KEY POINTS: Cortical integration of sensory inputs is crucial for dexterous movement. Short-latency somatosensory afferent inhibition of motor cortical output is typically produced by peripheral whole-nerve stimulation. We exploited intraneural multichannel electrodes used to provide sensory feedback for prosthesis control to assess whether and how selective intraneural sensory stimulation affects sensorimotor cortical circuits in humans. Activation of the primary somatosensory cortex (S1) was explored by recording scalp somatosensory evoked potentials. Sensorimotor integration was tested by measuring the inhibitory effect of the afferent stimulation on the output of the primary motor cortex (M1) generated by transcranial magnetic stimulation. We demonstrate in humans that selective intraneural sensory stimulation elicits a measurable activation of S1 and that it inhibits the output of M1 at the same time range of whole-nerve superficial stimulation.

Transcranial alternating current stimulation modulates cortical processing of somatosensory information in a frequency- and time-specific manner.

Neural oscillations can be modulated by non-invasive brain stimulation techniques, including transcranial alternating current stimulation (tACS). However, direct evidence of tACS effects at the cortical level in humans is still limited. In a tACS-electroencephalography co-registration setup, we investigated the ability of tACS to modulate cortical somatosensory information processing as assessed by somatosensory-evoked potentials (SEPs). To better elucidate the neural substrates of possible tACS effects we also recorded peripheral and spinal SEPs components, high-frequency oscillations (HFOs), and long-latency reflexes (LLRs). Finally, we studied whether changes were limited to the stimulation period or persisted thereafter. SEPs, HFOs, and LLRs were recorded during tACS applied at individual mu and beta frequencies and at the theta frequency over the primary somatosensory cortex (S1). Sham-tACS was used as a control condition. In a separate experiment, we assessed the time course of mu-tACS effects by recording SEPs before (T0), during (T1), and 1 min (T2) and 10 min (T3) after stimulation. Mu-tACS increased the amplitude of the N20 component of SEPs compared to both sham and theta-tACS. No differences were found between sham, beta-, and theta-tACS conditions. Also, peripheral and spinal SEPs, P25, HFOs, and LLRs did not change during tACS. Finally, mu-tACS-induced modulation of N20 amplitude specifically occurred during stimulation (T1) and vanished afterwards (i.e., at T2 and T3). Our findings suggest that TACS applied at the individual mu frequency is able to modulate early somatosensory information processing at the S1 level and the effect is limited to the stimulation period.