Neuronal Electrical Ongoing Activity as Cortical Areas Signature: An Insight from MNI Intracerebral Recording Atlas.

The time course of the neuronal activity in the brain network, the neurodynamics, reflects the structure and functionality of the generating neuronal pools. Here, using the intracranial stereo-electroencephalographic (sEEG) recordings of the public Montreal Neurological Institute (MNI) atlas, we investigated the neurodynamics of primary motor (M1), somatosensory (S1) and auditory (A1) cortices measuring power spectral densities (PSD) and Higuchi fractal dimension (HFD) in the same subject (M1 vs. S1 in 16 subjects, M1 vs. A1 in 9, S1 vs. A1 in 6). We observed specific spectral features in M1, which prevailed above beta band, S1 in the alpha band, and A1 in the delta band. M1 HFD was higher than S1, both higher than A1. A clear distinction of neurodynamics properties of specific primary cortices supports the efforts in cortical parceling based on this expression of the local cytoarchitecture and connectivity. In this perspective, we selected within the MNI intracortical database a first set of primary motor, somatosensory and auditory cortices' representatives to query in recognizing ongoing patterns of neuronal communication. Potential clinical impact stands primarily in exploiting such exchange patterns to enhance the efficacy of neuromodulation intervention to cure symptoms secondary to neuronal activity unbalances.

Effects on Motor Control of Personalized Neuromodulation Against Multiple Sclerosis Fatigue.

Fatigue is a hidden symptom of Multiple Sclerosis (MS) disease that nevertheless impacts severely on patients' everyday life. Evidence indicates the involvement of the sensorimotor network and its inter-nodes communication at the basis of this symptom. Two randomized controlled trials (RCTs) showed that the personalized neuromodulation called Fatigue Relief in Multiple Sclerosis (FaReMuS) efficaciously fights multiple sclerosis (MS) fatigue. By this Proof of Concept study, we tested whether FaReMuS reverts the alteration of the brain-muscular synchronization previously observed occurring with fatigue. The cortico muscular coherence (CMC) was studied in 11 patients before and after FaReMuS, a 5-day tDCS (1.5 mA, 15 min per day) anodal over the whole body's somatosensory representation (S1) via a personalized MRI-based electrode (35 cm2) against the occipital cathode (70 cm2). Before FaReMuS, the CMC was observed at a mean frequency of 31.5 ± 1.6 Hz (gamma-band) and positively correlated with the level of fatigue (p = .027). After FaReMuS, fatigue reduced in average of 28% ± 33% the baseline level, and the CMC frequency reduced to 26.6 ± 1.5 Hz (p = .022), thus forthcoming the physiological beta-band as observed in healthy people. The personalized S1 neuromodulation treatment, ameliorating the central-peripheral communication that subtends simple everyday movements, supports the appropriateness of neuromodulations aiming at increasing the parietal excitability in fighting MS fatigue. The relationship between central-peripheral features and fatigue profile strengthens a central more than peripheral origin of the symptom.

The developing role of transparent surfaces in children's spatial representation.

Children adeptly use environmental boundaries to navigate. But how do they represent surfaces as boundaries, and how does this change over development? To investigate the effects of boundaries as visual and physical barriers, we tested spatial reorientation in 160 children (2-7 year-olds) in a transparent rectangular arena (Condition 1). In contrast with their consistent success using opaque surfaces (Condition 2), children only succeeded at using transparent surfaces at 5-7 years of age. These results suggest a critical role of visually opaque surfaces in early spatial coding and a developmental change around the age of five in representing locations with respect to transparent surfaces. In application, these findings may inform our usage of windows and glass surfaces in designing and building environments occupied by young children.

Does a row of objects comprise a boundary? How children miss the forest for the trees in spatial navigation.

Unlike children's early ability to navigate by continuous boundaries, their ability to extract geometric information from an array of objects emerges gradually over childhood. To investigate children's developing representation of object arrays for navigation and its relation to their mental representation of the global spatial layout, reorientation behavior was tested in 146 children (4-9 years, 78 male children and 68 female children, Italian) with rectangular arrays made up of 20 objects. Posttest questions on children's spatial language and their mental and pictorial representation of the environment were administered. Although children of all ages navigated by the geometry of continuous boundary-like arrays, they only succeeded with separated object arrays at around 7 years of age. This developmental change was predicted by children's individual ability to extract the abstract geometry of the spatial layout in a two-dimensional picture of the room. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

On the Homology of the Dominant and Non-Dominant Corticospinal Tracts: A Novel Neurophysiological Assessment.

OBJECTIVES: The homology of hemispheric cortical areas plays a crucial role in brain functionality. Here, we extend this concept to the homology of the dominant and non-dominant hemi-bodies, investigating the relationship of the two corticospinal tracts (CSTs). The evoked responses provide an estimate of the number of in-phase recruitments via their amplitude as a suitable indicator of the neuronal projections' integrity. An innovative concept derived from experience in the somatosensory system is that their morphology reflects the recruitment pattern of the whole circuit. METHODS: CST homology was assessed via the Fréchet distance between the morphologies of motor-evoked potentials (MEPs) using a transcranial magnetic stimulation (TMS) in the homologous left- and right-hand first dorsal interosseous muscles of 40 healthy volunteers (HVs). We tested the working hypothesis that the inter-side Fréchet distance was higher than the two intra-side distances. RESULTS: In addition to a clear confirmation of the working hypothesis (p < 0.0001 for both hemi-bodies) verified in all single subjects, we observed that the intra-side Fréchet distance was higher for the dominant than the non-dominant one. Interhemispheric morphology similarity increased with right-handedness prevalence (p = 0.004). CONCLUSIONS: The newly introduced measure of circuit recruitment patterning represents a potential benchmark for the evaluation of inter-lateral mechanisms expressing the relationship between homologous hemilateral structures subtending learning and suggests that variability in recruitment patterning physiologically increases in circuits expressing greater functionality.

Effects on Corticospinal Tract Homology of Faremus Personalized Neuromodulation Relieving Fatigue in Multiple Sclerosis: A Proof-of-Concept Study.

OBJECTIVES: Fatigue in multiple sclerosis (MS) is a frequent and invalidating symptom, which can be relieved by non-invasive neuromodulation, which presents only negligible side effects. A 5-day transcranial direct-current stimulation, 15 min per day, anodically targeting the somatosensory representation of the whole body against a larger occipital cathode was efficacious against MS fatigue (fatigue relief in multiple sclerosis, Faremus treatment). The present proof-of-concept study tested the working hypothesis that Faremus S1 neuromodulation modifies the homology of the dominant and non-dominant corticospinal (CST) circuit recruitment. METHODS: CST homology was assessed via the Fréchet distance between the morphologies of motor potentials (MEPs) evoked by transcranial magnetic stimulation in the homologous left- and right-hand muscles of 10 fatigued MS patients before and after Faremus. RESULTS: In the absence of any change in MEP features either as differences between the two body sides or as an effect of the treatment, Faremus changed in physiological direction the CST's homology. Faremus effects on homology were more evident than recruitment changes within the dominant and non-dominant sides. CONCLUSIONS: The Faremus-related CST changes extend the relevance of the balance between hemispheric homologs to the homology between body sides. With this work, we contribute to the development of new network-sensitive measures that can provide new insights into the mechanisms of neuronal functional patterning underlying relevant symptoms.

Home treatment against fatigue in multiple sclerosis by a personalized, bilateral whole-body somatosensory cortex stimulation.

BACKGROUND: Fatigue in multiple sclerosis (MS) is a highly invalidating symptom with no pharmacological efficacious therapies, which furthermore present frequent severe side effects. In two previous randomized controlled trials we observed the efficacy of a personalized neuromodulation treatment consisting of a personalized transcranial Direct Current Stimulation (tDCS) for 15 min per day for 5 days (Faremus). METHODS: By this medical-device phase II study, we aimed at assessing the feasibility, acceptance, safety and efficacy of Faremus treatment when applied at patients' home. We considered the efficacy as primary outcome assessed by a reduction of fatigue levels measured by Modified Fatigue Impact Scale (mFIS) scored before and after the treatment. Primary outcome determined the sample size estimate. Individual ad-hoc questionnaires quantified the acceptance, safety and side effects during the treatment. RESULTS: All 15 patients completed the treatment, reporting optimal acceptance and safety on using Faremus at their home without side-effects. The treatment ameliorated fatigue symptoms more than 20% of baseline in 10 out of the 15 patients and of 37% on average, with a corresponding effect size 1.21. CONCLUSIONS: Faremus personalized electroceutical intervention, a 5-days anodal tDCS over the bilateral whole-body somatosensory cortex, is well accepted and can be feasibly, safely, and efficaciously applied at patients' home, offering a comfortable treatment by reducing the need to travel when fatigue-related symptoms hamper the quality of life.

Corticomuscular Coherence Dependence on Body Side and Visual Feedback.

Physiological movement develops on the basis of sensorimotor integration through synchronisation between the copy of signals sent to the effector muscles and the incoming flow of sensory information. Our aim is to study corticomuscular coherence (CMC), the most widely used measure of synchronization between brain and muscle electrical activities, in dependence on the level of visual feedback and the executing body side. We analysed CMC in 18 healthy volunteers while performing a weak isometric handgrip of an air bulb with either the right or the left hand, in either the presence or absence of visual feedback on the exerted pressure. The absence of visual feedback decreased the CMC peak frequency from 27 Hz to 23 Hz (p < 0.001), increased the CMC peak amplitude from 0.05 to 0.07 (p = 0.005) and decreased the electroencephalographic beta band power (p = 0.005). None of these measures changed in dependence on the performing hand (p > 0.2 consistently). The lack of dependence of CMC on the controlled hand involved in the movement can be considered in agreement with small hemispheric asymmetries of hand representations in primary sensorimotor cortices. Modulation of visual information changed corticomuscular synchronizations and cortical involvement, reflecting the crucial role of gaze in human behaviour. Given the fundamental role of sensory integration in motor execution, the availability of a simple index sensitive to modulations of perceptual afferents may prove useful in determining the use or the monitoring of the effects of sensory enrichments in personalized rehabilitation.

Normalized compression distance to measure cortico-muscular synchronization.

The neuronal functional connectivity is a complex and non-stationary phenomenon creating dynamic networks synchronization determining the brain states and needed to produce tasks. Here, as a measure that quantifies the synchronization between the neuronal electrical activity of two brain regions, we used the normalized compression distance (NCD), which is the length of the compressed file constituted by the concatenated two signals, normalized by the length of the two compressed files including each single signal. To test the NCD sensitivity to physiological properties, we used NCD to measure the cortico-muscular synchronization, a well-known mechanism to control movements, in 15 healthy volunteers during a weak handgrip. Independently of NCD compressor (Huffman or Lempel Ziv), we found out that the resulting measure is sensitive to the dominant-non dominant asymmetry when novelty management is required (p = 0.011; p = 0.007, respectively) and depends on the level of novelty when moving the non-dominant hand (p = 0.012; p = 0.024). Showing lower synchronization levels for less dexterous networks, NCD seems to be a measure able to enrich the estimate of functional two-node connectivity within the neuronal networks that control the body.

tDCS randomized controlled trials in no-structural diseases: a quantitative review.

The increasing number and quality of randomized controlled trials (RCTs) employing transcranial direct current stimulation (tDCS) denote the rising awareness of neuroscientific community about its electroceutical potential and opening to include these treatments in the framework of medical therapies under the indications of the international authorities. The purpose of this quantitative review is to estimate the recommendation strength applying the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) criteria and PICO (population, intervention, comparison, outcome) model values for effective tDCS treatments on no-structural diseases, and to provide an estimate of Sham effect for future RCTs. Applying GRADE evaluation pathway, we searched in literature the tDCS-based RCTs in psychophysical diseases displaying a major involvement of brain electrical activity imbalances. Three independent authors agreed on Class 1 RCTs (18 studies) and meta-analyses were carried out using a random-effects model for pathologies sub-selected based on PICO and systemic involvement criteria. The meta-analysis integrated with extensive evidence of negligible side effects and low-cost, easy-to-use procedures, indicated that tDCS treatments for depression and fatigue in Multiple Sclerosis ranked between moderately and highly recommendable. For these interventions we reported the PICO variables, with left vs. right dorsolateral prefrontal target for 30 min/10 days against depression and bilateral somatosensory vs occipital target for 15 min/5 days against MS fatigue. An across-diseases meta-analysis devoted to the Sham effect provided references for power analysis in future tDCS RCTs on these clinical conditions. High-quality indications support tDCS as a promising tool to build electroceutical treatments against diseases involving neurodynamics alterations.