Novel approaches to motoneuron disease/ALS treatment using non-invasive brain and spinal stimulation: IFCN handbook chapter.

Non-invasive brain stimulation techniques have been exploited in motor neuron disease (MND) with multifold objectives: to support the diagnosis, to get insights in the pathophysiology of these disorders and, more recently, to slow down disease progression. In this review, we consider how neuromodulation can now be employed to treat MND, with specific attention to amyotrophic lateral sclerosis (ALS), the most common form with upper motoneuron (UMN) involvement, taking into account electrophysiological abnormalities revealed by human and animal studies that can be targeted by neuromodulation techniques. This review article encompasses repetitive transcranial magnetic stimulation methods (including low-frequency, high-frequency, and pattern stimulation paradigms), transcranial direct current stimulation as well as experimental findings with the newer approach of trans-spinal direct current stimulation.

Targeting motor cortex high-excitability states defined by functional connectivity with real-time EEG-TMS.

We tested previous post-hoc findings indicating a relationship between functional connectivity (FC) in the motor network and corticospinal excitability (CsE), in a real-time EEG-TMS experiment in healthy participants. We hypothesized that high FC between left and right motor cortex predicts high CsE. FC was quantified in real-time by single-trial phase-locking value (stPLV), and TMS single pulses were delivered based on the current FC.

Closed-loop brain stimulation augments fear extinction in male rats.

Dysregulated fear reactions can result from maladaptive processing of trauma-related memories. In post-traumatic stress disorder (PTSD) and other psychiatric disorders, dysfunctional extinction learning prevents discretization of trauma-related memory engrams and generalizes fear responses. Although PTSD may be viewed as a memory-based disorder, no approved treatments target pathological fear memory processing.

Brain-oscillation-synchronized stimulation to enhance motor recovery in early subacute stroke: a randomized controlled double-blind three- arm parallel-group exploratory trial comparing personalized, non- personalized and sham repetitive transcranial magnetic stimulation (Acronym: BOSS-STROKE).

Background: Stroke is a major cause of death and the most frequent cause of permanent disability in western countries. Repetitive transcranial brain stimulation (rTMS) has been used to enhance neuronal plasticity after stroke, yet with only moderate effect sizes. Here we will apply a highly innovative technology that synchronizes rTMS to specific brain states identified by real-time analysis of electroencephalography.

Reinstating olfactory bulb-derived limbic gamma oscillations alleviates depression-like behavioral deficits in rodents.

Although the etiology of major depressive disorder remains poorly understood, reduced gamma oscillations is an emerging biomarker. Olfactory bulbectomy, an established model of depression that reduces limbic gamma oscillations, suffers from non-specific effects of structural damage. Here, we show that transient functional suppression of olfactory bulb neurons or their piriform cortex efferents decreased gamma oscillation power in limbic areas and induced depression-like behaviors in rodents.

Corticospinal excitability is highest at the early rising phase of sensorimotor µ-rhythm.

Alpha oscillations are thought to reflect alternating cortical states of excitation and inhibition. Studies of perceptual thresholds and evoked potentials have shown the scalp EEG negative phase of the oscillation to correspond to a short-lasting low-threshold and high-excitability state of underlying visual, somatosensory, and primary motor cortex. The negative peak of the oscillation is assumed to correspond to the state of highest excitability based on biophysical considerations and considerable effort has been made to improve the extraction of a predictive signal by individually optimizing EEG montages.

Reduced MC4R signaling alters nociceptive thresholds associated with red hair.

Humans and mice with natural red hair have elevated basal pain thresholds and an increased sensitivity to opioid analgesics. We investigated the mechanisms responsible for higher nociceptive thresholds in red-haired mice resulting from a loss of melanocortin 1 receptor (MC1R) function and found that the increased thresholds are melanocyte dependent but melanin independent. MC1R loss of function decreases melanocytic proopiomelanocortin transcription and systemic melanocyte-stimulating hormone (MSH) levels in the plasma of red-haired ( ) mice.

Closed-loop stimulation of the medial septum terminates epileptic seizures.

Temporal lobe epilepsy with distributed hippocampal seizure foci is often intractable and its secondary generalization might lead to sudden death. Early termination through spatially extensive hippocampal intervention is not feasible directly, because of the large size and irregular shape of the hippocampus. In contrast, the medial septum is a promising target to govern hippocampal oscillations through its divergent connections to both hippocampi.

Spike-and-Wave Discharges Are Not Pathological Sleep Spindles, Network-Level Aspects of Age-Dependent Absence Seizure Development in Rats.

Spike-and-wave discharges (SWDs) of absence epilepsy are considered as pathologic alterations of sleep spindles; however, their network-level relationship has never been convincingly revealed. In order to observe the development and generalization of the thalamocortical SWDs and the concomitant alterations of sleep related oscillations, we performed local field potential (LFP) and single unit recordings in rats for three months during their maturation. We found that while SWDs and spindles look similar in young, they become different with maturation and shift to appear in different brain states.

Aging Impairs Cerebrovascular Reactivity at Preserved Resting Cerebral Arteriolar Tone and Vascular Density in the Laboratory Rat.

The age-related (mal)adaptive modifications of the cerebral microvascular system have been implicated in cognitive impairment and worse outcomes after ischemic stroke. The magnitude of the hyperemic response to spreading depolarization (SD), a recognized principle of ischemic lesion development has also been found to be reduced by aging. Here, we set out to investigate whether the SD-coupled reactivity of the pial arterioles is subject to aging, and whether concomitant vascular rarefaction may contribute to the age-related insufficiency of the cerebral blood flow (CBF) response.

Epidemiologic characteristics of infection in southeast Hungary.

Background: Epidemiologic studies have revealed a decrease in the prevalence of () infection in Western Europe.

Aim: To obtain data regarding the prevalence of in Csongrád and Békés Counties in Hungary, evaluate the differences in its prevalence between urban and rural areas, and establish factors associated with positive seroprevalence.

Methods: One-thousand and one healthy blood donors [male/female: 501/500, mean age: 40 (19-65) years] were enrolled in this study.

Chronic Transcranial Electrical Stimulation and Intracortical Recording in Rats.

Transcranial electrical stimulation (TES) is a powerful and relatively simple approach to diffusely influence brain activity either randomly or in a closed-loop event-triggered manner. Although many studies are focusing on the possible benefits and side-effects of TES in healthy and pathologic brains, there are still many fundamental open questions regarding the mechanism of action of the stimulation. Therefore, there is a clear need for a robust and reproducible method to test the acute and the chronic effects of TES in rodents.

Direct effects of transcranial electric stimulation on brain circuits in rats and humans.

Transcranial electric stimulation is a non-invasive tool that can influence brain activity; however, the parameters necessary to affect local circuits in vivo remain to be explored. Here, we report that in rodents and human cadaver brains, ~75% of scalp-applied currents are attenuated by soft tissue and skull. Using intracellular and extracellular recordings in rats, we find that at least 1 mV/mm voltage gradient is necessary to affect neuronal spiking and subthreshold currents.

Sustained efficacy of closed loop electrical stimulation for long-term treatment of absence epilepsy in rats.

Closed-loop brain stimulation is a promising alternative to treat drug-resistant epilepsies. In contrast to optogenetic interventions, transcranial electrical stimulation (TES) does not require cellular modification of neurons to be effective, and it is less invasive compared to deep brain stimulation. Furthermore, on-demand TES of targeted brain regions allows the potential for normal function of these networks during interictal periods, a possibility that is eliminated by resective surgical treatment approaches.

Imaging reveals the focal area of spreading depolarizations and a variety of hemodynamic responses in a rat microembolic stroke model.

Spreading depolarizations (SDs) occur in stroke, but the spatial association between SDs and the corresponding hemodynamic changes is incompletely understood. We applied multimodal imaging to visualize the focal area of selected SDs, and hemodynamic responses with SDs propagating over the ischemic cortex. The intracarotid infusion of polyethylene microspheres (d=45 to 53 μm) produced multifocal ischemia in anesthetized rats (n=7).

Impact of aging on spreading depolarizations induced by focal brain ischemia in rats.

Spreading depolarization (SD) contributes to the ischemic damage of the penumbra. Although age is the largest predictor of stroke, no studies have examined age dependence of SD appearance. We characterized the electrophysiological and hemodynamic changes in young (6 weeks old, n = 7), middle-aged (9 months old, n = 6), and old (2 years old, n = 7) male Wistar rats during 30 minutes of middle cerebral artery occlusion (MCAO), utilizing multimodal imaging through a closed cranial window over the ischemic cortex: membrane potential changes (with a voltage-sensitive dye), cerebral blood volume (green light reflectance), and cerebral blood flow (CBF, laser-speckle imaging) were observed.

Photosynthetic reaction centers/ITO hybrid nanostructure.

Photosynthetic reaction center proteins purified from Rhodobacter sphaeroides purple bacterium were deposited on the surface of indium tin oxide (ITO), a transparent conductive oxide, and the photochemical/-physical properties of the composite were investigated. The kinetics of the light induced absorption change indicated that the RC was active in the composite and there was an interaction between the protein cofactors and the ITO. The electrochromic response of the bacteriopheophytine absorption at 771 nm showed an increased electric field perturbation around this chromophore on the surface of ITO compared to the one measured in solution.