Phase Dependency of the Human Primary Motor Cortex and Cholinergic Inhibition Cancelation during Beta tACS

The human motor cortex has a tendency to resonant activity at about 20 Hz so stimulation should more readily entrain neuronal populations at this frequency. We investigated whether and how different interneuronal circuits contribute to such resonance by using transcranial magnetic stimulation (TMS) during transcranial alternating current stimulation (tACS) at motor (20 Hz) and a nonmotor resonance frequency (7 Hz). We tested different TMS interneuronal protocols and triggered TMS pulses at different tACS phases. The effect of cholinergic short-latency afferent inhibition (SAI) was abolished by 20 Hz tACS, linking cortical beta activity to sensorimotor integration. However, this effect occurred regardless of the tACS phase. In contrast, 20 Hz tACS selectively modulated MEP size according to the phase of tACS during single pulse, GABAAergic short-interval intracortical inhibition (SICI) and glutamatergic intracortical facilitation (ICF). For SICI this phase effect was more marked during 20 Hz stimulation. Phase modulation of SICI also depended on whether or not spontaneous beta activity occurred at ~20 Hz, supporting an interaction effect between tACS and underlying circuit resonances. The present study provides in vivo evidence linking cortical beta activity to sensorimotor integration, and for beta oscillations in motor cortex being promoted by resonance in GABAAergic interneuronal circuits

Brain stimulation as a therapeutic tool in Amyotrophic Lateral Sclerosis: current status and interaction with mechanisms of altered cortical excitability

In the last 20 years, several modalities of neuromodulation, mainly based on non-invasive brain stimulation (NIBS) techniques, have been tested as a non-pharmacological therapeutic approach to slow disease progression in amyotrophic lateral sclerosis (ALS). In both sporadic and familial ALS cases, neurophysiological studies point to motor cortical hyperexcitability as a possible priming factor in neurodegeneration, likely related to dysfunction of both excitatory and inhibitory mechanisms. A trans-synaptic anterograde mechanism of excitotoxicity is thus postulated, causing upper and lower motor neuron degeneration. Specifically, motor neuron hyperexcitability and hyperactivity are attributed to intrinsic cell abnormalities related to altered ion homeostasis and to impaired glutamate and gamma aminobutyric acid gamma-aminobutyric acid (GABA) signaling. Several neuropathological mechanisms support excitatory and synaptic dysfunction in ALS; additionally, hyperexcitability seems to drive DNA-binding protein 43-kDA (TDP-43) pathology, through the upregulation of unusual isoforms directly contributing to ASL pathophysiology. Corticospinal excitability can be suppressed or enhanced using NIBS techniques, namely, repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), as well as invasive brain and spinal stimulation. Experimental evidence supports the hypothesis that the after-effects of NIBS are mediated by long-term potentiation (LTP)-/long-term depression (LTD)-like mechanisms of modulation of synaptic activity, with different biological and physiological mechanisms underlying the effects of tDCS and rTMS and, possibly, of different rTMS protocols. This potential has led to several small trials testing different stimulation interventions to antagonize excitotoxicity in ALS. Overall, these studies suggest a possible efficacy of neuromodulation in determining a slight reduction of disease progression, related to the type, duration, and frequency of treatment, but current evidence remains preliminary. Main limitations are the small number and heterogeneity of recruited patients, the limited "dosage" of brain stimulation that can be delivered in the hospital setting, the lack of a sufficient knowledge on the excitatory and inhibitory mechanisms targeted by specific stimulation interventions, and the persistent uncertainty on the key pathophysiological processes leading to motor neuron loss. The present review article provides an update on the state of the art of neuromodulation in ALS and a critical appraisal of the rationale for the application/optimization of brain stimulation interventions, in the light of their interaction with ALS pathophysiological mechanisms

Brachial palsy after deep sleep

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Effects of transcranial alternating current stimulation on repetitive finger movements in healthy humans

Transcranial alternating current stimulation (tACS) is a noninvasive neurophysiological technique that can entrain brain oscillations. Only few studies have investigated the effects of tACS on voluntary movements. We aimed to verify whether tACS, delivered over M1 at beta and gamma frequencies, has any effect on repetitive finger tapping as assessed by means of kinematic analysis. Eighteen healthy subjects were enrolled. Objective measurements of repetitive finger tapping were obtained by using a motion analysis system. M1 excitability was assessed by using single-pulse TMS and measuring the amplitude of motor-evoked potentials (MEPs). Movement kinematic measures and MEPs were collected during beta, gamma, and sham tACS and when the stimulation was off. Beta tACS led to an amplitude decrement (i.e., progressive reduction in amplitude) across the first ten movements of the motor sequence while gamma tACS had the opposite effect. The results did not reveal any significant effect of tACS on other movement parameters, nor any changes in MEPs. These findings demonstrate that tACS modulates finger tapping in a frequency-dependent manner with no concurrent changes in corticospinal excitability. The results suggest that cortical beta and gamma oscillations are involved in the motor control of repetitive finger movements

An open-label, one-arm, dose-escalation study to evaluate safety and tolerability of extremely low frequency magnetic fields in acute ischemic stroke

Extremely low frequency magnetic fields (ELF-MF) could be an alternative neuroprotective approach for ischemic stroke because preclinical studies have demonstrated their effects on the mechanisms underlying ischemic damage. The purpose of this open-label, one arm, dose-escalation, exploratory study is to evaluate the safety and tolerability of ELF-MF in patients with acute ischemic stroke. Within 48 hours from the stroke onset, patients started ELF-MF treatment, daily for 5 consecutive days. Clinical follow-up lasted 12 months. Brain MRI was performed before and 1 month after the treatment. The distribution of ELF-MF in the ischemic lesion was estimated by dosimetry. Six patients were stimulated, three for 45 min/day and three for 120 min/day. None of them reported adverse events. Clinical conditions improved in all the patients. Lesion size was reduced in one patient stimulated for 45 minutes and in all the patients stimulated for 120 minutes. Magnetic field intensity within the ischemic lesion was above 1 mT, the minimum value able to trigger a biological effect in preclinical studies. Our pilot study demonstrates that ELF-MF are safe and tolerable in acute stroke patients. A prospective, randomized, placebo-controlled, double-blind study will clarify whether ELF-MFs could represent a potential therapeutic approach

Neurobiological After-Effects of Low Intensity Transcranial Electric Stimulation of the Human Nervous System: From Basic Mechanisms to Metaplasticity

Non-invasive low-intensity transcranial electrical stimulation (tES) of the brain is an evolving field that has brought remarkable attention in the past few decades for its ability to directly modulate specific brain functions. Neurobiological after-effects of tES seems to be related to changes in neuronal and synaptic excitability and plasticity, however mechanisms are still far from being elucidated. We aim to review recent results from in vitro and in vivo studies that highlight molecular and cellular mechanisms of transcranial direct (tDCS) and alternating (tACS) current stimulation. Changes in membrane potential and neural synchronization explain the ongoing and short-lasting effects of tES, while changes induced in existing proteins and new protein synthesis is required for long-lasting plastic changes (LTP/LTD). Glial cells, for decades supporting elements, are now considered constitutive part of the synapse and might contribute to the mechanisms of synaptic plasticity. This review brings into focus the neurobiological mechanisms and after-effects of tDCS and tACS from in vitro and in vivo studies, in both animals and humans, highlighting possible pathways for the development of targeted therapeutic applications

Radial neck fractures in children: results when open reduction is indicated

BACKGROUND: Radial neck fractures in children are rare, representing 5% of all elbow pediatric fractures. Most are minimally displaced or nondisplaced. Severely displaced or angulated radial neck fractures often have poor outcomes, even after open reduction, and case series reported in literature are limited. The aim of the study is to analyze the outcomes of patients with a completely displaced and angulated fracture who underwent open reduction when closed reduction failed. METHODS: Between 2000 and 2009, 195 patients with radial neck fractures were treated in our institute. Twenty-four cases satisfied all the inclusion criteria and were evaluated clinically and radiologically at a mean follow-up of 7 years. At follow-up, the carrying angle in full elbow extension and the range of motion of the elbow and forearm were measured bilaterally. We recorded clinical results as good, fair, or poor according to the range of movement and the presence of pain. Radiographic evaluation documented the size of the radial head, the presence of avascular necrosis, premature physeal closure, and cubitus valgus. RESULTS: Statistical analysis showed that fair and poor results are directly correlated with loss of pronation-supination (P=0.001), reduction of elbow flexion-extension (P=0.001), increase of elbow valgus angle (P=0.002), necrosis of the radial head (P=0.001), premature physeal closure (P=0.01), and associated lesions (olecranon fracture with or without dislocation of the elbow) (P=0.002). DISCUSSION: In our cases, residual radial head deformity due to premature closure of the growth plate and avascular necrosis were correlated with a functional deficit. Associated elbow injury was coupled with a negative prognosis. In our series, about 25% of patients had fair and 20% had poor results. Outcomes were good in 55% and felt to represent a better outcome than if the fracture remained nonanatomically reduced with residual angulation and/or displacement of the radial head. This study reports the largest series of these fractures with a combination of significant angulation and displacement of the fracture requiring open reduction. We feel that open reduction is indicated when the head of the radius is completely displaced and without contact with the rim of the metaphysis

Idiopathic infratentorial superficial siderosis of the central nervous system: case report and review of literature

The superficial siderosis (SS) of the central nervous system (CNS) is a rare condition characterized by a wide range of neurological manifestations directly linked to an acquired iron-mediated neurodegeneration. First described more than 100 years ago, only recently SS has been divided into two distinct entities, according to the distribution of iron deposition in the CNS: cortical superficial siderosis (cSS) and infratentorial superficial siderosis (iSS). Here we describe an adult case of iSS, with detailed clinical and radiological features. Moreover, we extensively review the literature of SS, particularly focusing on the pathogenesis, clinical-radiological classification, diagnostic algorithm and treatment options of this rare condition

Corrigendum: oscillatory activities in neurological disorders of elderly: biomarkers to target for neuromodulation

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