Auditory Personalization of EMDR Treatment to Relieve Trauma Effects: A Feasibility Study [EMDR+].

According to the WHO (World Health Organization), Eye Movement Desensitization and Reprocessing (EMDR) is an elective therapy to treat people with post-traumatic stress disorders (PTSD). In line with the personalization of therapeutic strategies, through this pilot study, we assessed in people suffering from the effects of trauma the feasibility, safety, acceptance, and efficacy of EMDR enriched with sound stimulation (by administering neutral sounds synchronized with the guided bilateral alternating stimulation of the gaze) and musical reward (musical listening based on the patients' predisposition and personal tastes). Feasibility, quantified by the number of patients who completed the treatment, was excellent as this was the case in 12 out of the 12 enrolled people with psychological trauma. Safety and acceptance, assessed by self-compiled questionnaires, were excellent, with an absence of side effects and high satisfaction. Efficacy, quantified by the number of EMDR treatment sessions required to reach the optimal scores on the Subjective Units of Disturbance (SUD) and Validity of Cognition (VOC) scales typical of EMDR protocols, revealed an average duration of 8.5 (SD 1.2) sessions, which is well below the 12 sessions considered a standard EMDR treatment duration. EMDR+ appears to be a relevant personalization of EMDR, particularly in music-sensitive people, consolidating the therapeutic alliance through a multisensory communicative bond for trauma treatment.

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.

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.

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.

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.

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.