Electroencephalographic Responses Research Articles

Individual variation in the neurophysiological representation of negative emotions in virtual reality is shaped by sociability

Negative emotions play a dominant role in daily human life, and mentalizing and empathy are also basic sociability in social life. However, little is known regards the neurophysiological pattern of negative experiences in immersive environments and how people with different sociabilities respond to the negative emotional stimuli at behavioral and neural levels. The present study investigated the neurophysiological representation of negative affective experiences and whether such variations are associated with one's sociability. To address this question, we examined four types of negative emotions that frequently occurred in real life: angry, anxious, fearful, and helpless. We combined naturalistic neuroimaging under virtual reality, multimodal neurophysiological recording, and behavioral measures. Inter-subject representational similarity analysis was conducted to capture the individual differences in the neurophysiological representations of negative emotional experiences. The behavioral and neurophysiological indices revealed that although the emotion ratings were uniquely different, a similar electroencephalography response pattern across these negative emotions was found over the parieto-occipital electrodes. Furthermore, the neurophysiological representations indeed reflected interpersonal variations regarding mentalizing and empathic abilities. Our findings yielded a common pattern of neurophysiological responses toward different negative affective experiences in VR. Moreover, the current results indicate the potential of taking a sociability perspective for understanding the interpersonal variations in the neurophysiological representation of emotion.

Prefrontal reactivity to TMS perturbation as a toy model of mental health outcomes during the COVID-19 pandemic

Psychosocial hardships associated with the COVID-19 pandemic led many individuals to suffer adverse mental health consequences, however, others show no negative effects. We hypothesized that the electroencephalographic (EEG) response to transcranial magnetic stimulation (TMS) could serve as a toy-model of an individual's capacity to resist psychological stress, in this case linked to the COVID-19 pandemic. We analyzed data from 74 participants who underwent mental health monitoring and concurrent electroencephalography with transcranial magnetic stimulation of the left dorsolateral prefrontal cortex (L-DLPFC) and left inferior parietal lobule (L-IPL). Within the following 19 months, mental health was reassessed at three timepoints during lock-down confinement and different phases of de-escalation in Spain. Compared with participants who remained stable, those who experienced increased mental distress showed, months earlier, significantly larger late EEG responses locally after L-DLPFC stimulation (but not globally nor after L-IPL stimulation). This response, together with years of formal education, was significantly predictive of mental health status during the pandemic. These findings reveal that the effect of TMS perturbation offers a predictive toy model of psychosocial stress response, as exemplified by the COVID-19 pandemic.

Neural correlates of perceived emotions in human insula and amygdala for auditory emotion recognition

The emotional status of a speaker is an important non-linguistic cue carried by human voice and can be perceived by a listener in vocal communication. Understanding the neural circuits involved in processing emotions carried by human voice is crucial for understanding the neural basis of social interaction. Previous studies have shown that human insula and amygdala responded more selectively to emotional sounds than non-emotional sounds. However, it is not clear whether the neural selectivity to emotional sounds in these brain structures is determined by the emotion presented by a speaker which is associated with the acoustic properties of the sounds or by the emotion perceived by a listener. In this study, we recorded intracranial electroencephalography (iEEG) responses to emotional human voices while subjects performed emotion recognition tasks. We found that the iEEG responses of Heschl's gyrus (HG) and posterior insula were determined by the presented emotion, whereas the iEEG responses of anterior insula and amygdala were driven by the perceived emotion. These results suggest that the anterior insula and amygdala play a crucial role in conscious perception of emotions carried by human voice.

Electroencephalographic response to transient adaptation of vestibular perception.

When given a series of sinusoidal oscillations in which the two hemicycles have equal amplitude but asymmetric velocity, healthy subjects lose perception of the slower hemicycle (SHC), reporting a drift towards the faster hemicycle (FHC). This response is not reflected in the vestibular–ocular reflex, suggesting that the adaptation is of higher order. This study aimed to define EEG correlates of this adaptive response. Twenty‐five subjects underwent a series of symmetric or asymmetric oscillations and reported their perceived head orientation at the end using landmarks in the testing room; this was converted into total position error (TPE). Thirty‐two channel EEG was recorded before, during and after adaptation. Spectral power and coherence were calculated for the alpha, beta, delta and theta frequency bands. Linear mixed models were used to determine a region‐by‐condition effect of the adaptation. TPE was significantly greater in the asymmetric condition and reported error was always in the direction of the FHC. Regardless of condition, alpha desynchronised in response to stimulation, then rebounded back toward baseline values. This pattern was accelerated and attenuated in the prefrontal and occipital regions, respectively, in the asymmetric condition. Functional connectivity networks were identified in the beta and delta frequency bands; these networks, primarily comprising frontoparietal connections, were more coherent during asymmetric stimulation. These findings suggest that the temporary vestibulo‐perceptual ‘neglect’ induced by asymmetric vestibular stimulation may be mediated by alpha rhythms and frontoparietal attentional networks. The results presented further our understanding of brain rhythms and cortical networks involved in vestibular perception and adaptation. Key points Whole‐body asymmetric sinusoidal oscillations, which consist of hemicycles with equal amplitude but differing velocities, can induce transient ‘neglect’ of the slower hemicycle in the vestibular perception of healthy subjects.In this study, we aimed to elucidate EEG correlates of this ‘neglect’, thereby identifying a cortical role in vestibular perception and adaptation.We identified a desynchronisation–resynchronisation response in the alpha frequency band (8–14 Hz) that was accelerated in the prefrontal region and attenuated in the occipital region when exposed to asymmetric, as compared to symmetric, rotations.We additionally identified functional connectivity networks in the beta (14–30 Hz) and delta (1–4 Hz) frequency bands consisting primarily of frontoparietal connections.These results suggest a prominent role of alpha rhythms and frontoparietal attentional networks in vestibular perception and adaptation.

EEG microstate temporal Dynamics Predict depressive symptoms in College Students

Previous studies on resting-state electroencephalographic responses in patients with depressive disorders have identified electroencephalogram (EEG) parameters as potential biomarkers for the early detection and diagnosis of depressive disorders. However, these studies did not investigate the relationship between resting-state EEG microstates and the early detection of depressive symptoms in preclinical individuals. To explore the possible association between resting-state EEG microstate temporal dynamics and depressive symptoms among college students, EEG microstate analysis was performed on eyes-closed resting-state EEG data for approximately 5min from 34 undergraduates with high intensity of depressive symptoms and 34 age- and sex-matched controls with low intensity of depressive symptoms. Five microstate classes (A-E) were identified to best explain the datasets of both groups. Compared to controls, the mean duration, occurrence, and coverage of microstate class B increased significantly, whereas the occurrence and coverage of microstate classes D and E decreased significantly in individuals with high intensity of depressive symptoms. Additionally, the presence of microstate class B was positively correlated with participants' Beck Depression Inventory-II (BDI-II) scores, and the presence of microstate classes D and E were negatively correlated with their BDI-II scores. Further, individuals with high intensity of depressive symptoms had higher transition probabilities of A→B, B→A, B→C, B→D, and C→B, with lower transition probabilities of A→D, A→E, D→A, D→E, E→A, E→C, and E→D than controls. These results highlight resting-state EEG microstate temporal dynamics as potential biomarkers for the early detection and timely treatment of depression in college students.

Subjective Distance Estimates and Sense of Agency in Robotic Wheelchair Control

Sense of agency (SoA) refers to an individual’s awareness of their own actions. SoA studies seek to find objective indicators for the feeling of agency. These indicators, being related to the feeling of control, have practical application in vehicle design. However, they have not been investigated for actions related to the agent’s body movement inherent to steering a vehicle. In our study, participants operated a robotic wheelchair under three conditions: active control by a participant, direct control by the experimenter and remote control by the experimenter. In each trial, a participant drove the wheelchair until a sound signal occurred, after which they stopped the wheelchair and estimated the travelled distance. The subjective estimates were significantly greater when participants operated the wheelchair by themselves. This result contrasts with observations under static settings in previous studies. In an additional study on the electroencephalographic response to a sound presented at a random time after movement onset, the observed latencies in the N1 component implied that participants might have a higher sense of control when they drove the wheelchair. The proposed methodology might become useful to indirectly assess the degree of operator control of a vehicle, primarily in the field of rehabilitation technologies.

Children with autism spectrum disorder show atypical electroencephalographic response to processing contextual incongruencies

Children with autism spectrum disorder (ASD) experience difficulties with social communication, making it challenging to interpret contextual information that aids in accurately interpreting language. To investigate how the brain processes the contextual information and how this is different in ASD, we compared event-related potentials (ERPs) in response to processing visual and auditory congruent and incongruent information. Two groups of children participated in the study: 37 typically developing children and 15 children with ASD (age range = 6 to 12). We applied a language task involving auditory sentences describing congruent or incongruent images. We investigated two ERP components associated with language processing: the N400 and P600. Our results showed how children with ASD present significant differences in their neural responses in comparison with the TD group, even when their reaction times and correct trials are not significantly different from the TD group.

SAR-Connect: A Socially Assistive Robotic System to Support Activity and Social Engagement of Older Adults.

Multi-domain activities that incorporate physical, cognitive, and social stimuli can enhance older adults' overall health and quality of life. Several robotic platforms have been developed to provide these therapies in a quantifiable manner to complement healthcare personnel in resource-strapped long-term care settings. However, these platforms are primarily limited to one-to-one human robot interaction (HRI) and thus do not enhance social interaction. In this paper, we present a novel HRI framework and a realized platform called SAR-Connect to foster robot-mediated social interaction among older adults through carefully designed tasks that also incorporate physical and cognitive stimuli. SAR-Connect seamlessly integrates a humanoid robot with a virtual reality-based activity platform and a multimodal data acquisition module including game interaction, audio, visual and electroencephalography responses of the participants. Results from a laboratory-based user study with older adults indicates the potential of SAR-Connect that showed this system could 1) involve one or multiple older adults to perform multi-domain activities and provide dynamic guidance, 2) engage them in the robot-mediated task and foster human-human interaction, and 3) quantify their social and activity engagement from multiple sensory modalities.

The Association of P300 Components With Clinical Characteristics and Efficacy of Pharmacotherapy in Alcohol Use Disorder.

PurposeThe purpose of this study is to explore the association of P300 components with clinical characteristics and efficacy of pharmacotherapy in alcohol use disorder (AUD).MethodsOne hundred fifty-one AUD patients and 96 healthy controls were recruited and evaluated for the symptoms of depression, anxiety, sleep, and cognitive function by the Alcohol Use Disorders Identification Test (AUDIT), the 9-item Patient Health Questionnaire (PHQ-9), the 7-item Generalized Anxiety Disorder scale (GAD-7), the Pittsburgh Sleep Quality Index (PSQI), Digit Symbol Substitution test (DSST), and event-related potential P300, which is one of the averaged scalp electroencephalography responses time-locked to specific events. Among the AUD group, 101 patients finished an 8-week pharmacotherapy and were evaluated for the above data at post-intervention.Results1. At baseline, AUD patients had higher scores of AUDIT, PHQ-9, GAD-7, PSQI, and P300 latency at Cz, Pz, and Fz and lower DSST score and smaller P300 amplitudes at Fz, Cz, and Pz compared with controls. P300 components correlated significantly with alcohol dose and score of AUDIT, PHQ-9, GAD-7, PSQI, and DSST. 2. After 8 weeks' treatment, there were significant changes for the P300 components; alcohol dose; and score of AUDIT, PHQ-9, GAD-7, PSQI, and DSST. Variables at baseline, including P300 amplitudes at Fz, Cz, and Pz; latency of Fz and Pz; alcohol dose; and scores of PHQ-9, GAD-7, PSQI, and DSST, were significantly associated with changes of reduction rate of AUDIT scores. However, P300 amplitudes at Fz, Cz, and Pz in AUD patients after 8-week treatment were still significantly shorter than healthy controls (HCs), and P300 latencies at Fz, Cz, and Pz were significantly longer than HCs. 3. When validated area under the receiver operating characteristic curve (AUC) was over 0.80, the baseline variables including amplitudes at Cz and Pz, alcohol dose, and scores of PSQI could predict the changes of reduction rate of AUDIT score.ConclusionP300 amplitudes and latencies at Fz, Cz, and Pz could be used as biological markers for evaluating the clinical characters and severity of AUD. P300 amplitudes at Cz and Pz, sleep condition, and cognitive function at baseline could predict the efficacy of pharmacotherapy for AUD patients.

Pre-stimulus alpha-band phase gates early visual cortex responses

Alpha-band (8-13 Hz) oscillations have been shown to phasically inhibit perceptual reports in human observers, yet the underlying physiological mechanism of this effect is debated. According to contrasting models, based primarily on animal experiments, alpha activity is thought to either originate from specialized cells in the visual thalamus and periodically inhibit the relay of visual information to the primary visual cortex (V1) in a feedforward manner, or to propagate from higher visual areas back to V1 in a feedback manner. Human neurophysiological evidence in favor of either hypothesis, both, or neither, has been limited. To help address this issue, we explored the link between pre-stimulus alpha phase and visual electroencephalography (EEG) responses thought to arise from afferent input onto human V1. Specially-designed visual stimuli were used to elicit large amplitude C1 event-related potentials (ERP), with polarity, topography, and timing indicative of striate genesis. Single-trial circular-linear associations between pre-stimulus phase and post-stimulus global field power (GFP) during the C1 time window revealed significant effects peaking in the alpha frequency band. Control analyses ruling out the potential confound of post-stimulus data bleeding into the pre-stimulus window demonstrated that GFP amplitude decreases as pre-stimulus alpha phase deviates from an individual's preferred phase. These findings demonstrate an early locus – suggesting that the phase of pre-stimulus alpha oscillations could modulate visual processing by gating the feedforward flow of sensory input between the thalamus and V1, although other models are potentially compatible.

Cold evoked potentials elicited by rapid cooling of the skin in young and elderly healthy individuals

Cold-evoked potentials (CEPs) constitute a novel electrophysiological tool to assess cold-specific alterations in somatosensory function. As an important step towards the clinical implementation of CEPs as a diagnostic tool, we evaluated the feasibility and reliability of CEPs in response to rapid cooling of the skin (−300 °C/s) and different stimulation sites in young and elderly healthy individuals. Time-locked electroencephalographic responses were recorded from at vertex in fifteen young (20–40 years) and sixteen elderly (50–70 years), individuals in response to 15 rapid cold stimuli (−300 °C/s) applied to the skin of the hand dorsum, palm, and foot dorsum. High CEP proportions were shown for young individuals at all sites (hand dorsum/palm: 100% and foot: 79%) and elderly individuals after stimulation of the hand dorsum (81%) and palm (63%), but not the foot (44%). Depending on the age group and stimulation site, test–retest reliability was “poor” to “substantial” for N2P2 amplitudes and N2 latencies. Rapid cooling of the skin enables the recording of reliable CEPs in young individuals. In elderly individuals, CEP recordings were only robust after stimulation of the hand, but particularly challenging after stimulation of the foot. Further improvements in stimulation paradigms are warranted to introduce CEPs for clinical diagnostics.

Capacity for consciousness under ketamine anaesthesia is selectively associated with activity in posteromedial cortex in rats.

It remains unclear how specific cortical regions contribute to the brain’s overall capacity for consciousness. Clarifying this could help distinguish between theories of consciousness. Here, we investigate the association between markers of regionally specific (de)activation and the brain’s overall capacity for consciousness. We recorded electroencephalographic responses to cortical electrical stimulation in six rats and computed Perturbational Complexity Index state-transition (PCIST), which has been extensively validated as an index of the capacity for consciousness in humans. We also estimated the balance between activation and inhibition of specific cortical areas with the ratio between high and low frequency power from spontaneous electroencephalographic activity at each electrode. We repeated these measurements during wakefulness, and during two levels of ketamine anaesthesia: with the minimal dose needed to induce behavioural unresponsiveness and twice this dose. We found that PCIST was only slightly reduced from wakefulness to light ketamine anaesthesia, but dropped significantly with deeper anaesthesia. The high-dose effect was selectively associated with reduced high frequency/low frequency ratio in the posteromedial cortex, which strongly correlated with PCIST. Conversely, behavioural unresponsiveness induced by light ketamine anaesthesia was associated with similar spectral changes in frontal, but not posterior cortical regions. Thus, activity in the posteromedial cortex correlates with the capacity for consciousness, as assessed by PCIST, during different depths of ketamine anaesthesia, in rats, independently of behaviour. These results are discussed in relation to different theories of consciousness.

Emotive Response to a Hybrid-Face Robot and Translation to Consumer Social Robots

We present the conceptual formulation, design, fabrication, control and commercial translation of an IoT enabled social robot as mapped through validation of human emotional response to its affective interactions. The robot design centres on a humanoid hybrid-face that integrates a rigid faceplate with a digital display to simplify conveyance of complex facial movements while providing the impression of three-dimensional depth. We map the emotions of the robot to specific facial feature parameters, characterise recognisability of archetypical facial expressions, and introduce pupil dilation as an additional degree of freedom for emotion conveyance. Human interaction experiments demonstrate the ability to effectively convey emotion from the hybrid-robot face to humans. Conveyance is quantified by studying neurophysiological electroencephalography (EEG) response to perceived emotional information as well as through qualitative interviews. Results demonstrate core hybrid-face robotic expressions can be discriminated by humans (80%+ recognition) and invoke face-sensitive neurophysiological event-related potentials such as N170 and Vertex Positive Potentials in EEG. The hybrid-face robot concept has been modified, implemented, and released by Emotix Inc in the commercial IoT robotic platform Miko (‘My Companion’), an affective robot currently in use for human-robot interaction with children. We demonstrate that human EEG responses to Miko emotions are comparative to that of the hybrid-face robot validating design modifications implemented for large scale distribution. Finally, interviews show above 90% expression recognition rates in our commercial robot. We conclude that simplified hybrid-face abstraction conveys emotions effectively and enhances human-robot interaction.

Quantifying arousal and awareness in altered states of consciousness using interpretable deep learning

Consciousness can be defined by two components: arousal (wakefulness) and awareness (subjective experience). However, neurophysiological consciousness metrics able to disentangle between these components have not been reported. Here, we propose an explainable consciousness indicator (ECI) using deep learning to disentangle the components of consciousness. We employ electroencephalographic (EEG) responses to transcranial magnetic stimulation under various conditions, including sleep (n = 6), general anesthesia (n = 16), and severe brain injury (n = 34). We also test our framework using resting-state EEG under general anesthesia (n = 15) and severe brain injury (n = 34). ECI simultaneously quantifies arousal and awareness under physiological, pharmacological, and pathological conditions. Particularly, ketamine-induced anesthesia and rapid eye movement sleep with low arousal and high awareness are clearly distinguished from other states. In addition, parietal regions appear most relevant for quantifying arousal and awareness. This indicator provides insights into the neural correlates of altered states of consciousness.

The effect of the degree and location of danger in traffic hazard perception: an ERP study

The aim of this study is to explore the influence of the degree and location of the danger of traffic hazards on the neural reaction process. 26 automobile drivers were asked to look at the pictures and press buttons on the pictures unrelated to traffic. Electroencephalography responses to traffic-related images were recorded and analyzed. It was found that danger in the central visual region induced a larger amplitude of the N100 component than in the peripheral visual region and the trend of different hazard levels was consistent. The danger in the central visual area also induced a larger amplitude of the P200 component than in the peripheral vision area. In addition, when the danger appeared in the central visual area (0°), the P200 amplitude induced by the low-hazard situation was smaller than that of the high-hazard situation. When the danger appeared in the peripheral visual area (7°), the P200 amplitude induced by the low-hazard situation was larger than that of the high-hazard situation. Finally, the presence of danger evoked a larger amplitude of the P300 component in the peripheral visual area than in the central visual area and the P300 amplitude was larger in the low-hazard situation than in the high-hazard situation. The results suggest that hazards are more easily processed in the central visual area during the early stage of automatic perception. In the later hazard evaluation stage, the hazard in the central visual area and the high-hazard situation were more easily processed.

P2 Manifests Subjective Evaluation of Reward Processing Under Social Comparison.

Several recent studies have found that when the other’s gain is greater, even subjects’ reward may seem like a loss and lead to a negative experience. These studies indicate the complexity of reward evaluation in the context of social comparison. The satisfaction rating of reward outcome not only depends on objective social comparison but also on subjective evaluation. However, less is known about the neural time course of subjective evaluation. Therefore, we employed a 2 (subjective evaluation: advantageous vs. disadvantageous) × 2 (comparison direction: upward vs. downward) within-subjects factorial design, in which we manipulated the reward distribution for the subjects. Electroencephalography (EEG) responses were recorded, while two subjects concurrently but independently performed a simple dot-estimation task that entailed monetary rewards. Behavioral results showed that the subjects were more satisfied with the advantageous distribution, regardless of upward or downward comparison. The analysis of event-related potentials (ERPs) revealed that disadvantageous distribution elicited a larger P2 than advantageous distribution, and this effect was not modulated by comparison direction. In contrast, the late positive potential (LPP) showed an effect of comparison direction independent of subjective evaluation. The data suggest that subjective evaluation acts upon the early stage of reward processing and manifests in the P2 component, whereas social comparison plays a role in the later appraisal process.

Neural processing of moral content reflects moral identity in 10‐year‐old children

Middle childhood seems to be crucial for the emergence of a moral identity, that is, an evaluative stance of how important it is for someone's sense of self to be moral. This study investigates the effects of moral identity on the neural processing of moral content in 10-year-old children. Participants were presented with scenes portraying prosocial and antisocial behavior, while electroencephalographic responses were collected. Analyses of event-related potentials (ERPs) showed that, for children with a strong moral identity, antisocial scenes elicited a greater early posterior negativity (EPN) as compared to prosocial scenes. Thus, for children with a strong moral identity, antisocial scenes capture more attentional resources than prosocial ones in early processing stages. In contrast to previous findings with adults, the implicit moral self-concept was not related to any ERP differences. Overall, the results show that, even in its developmental emergence, moral identity relates to the neurocognitive processing of third-party moral content. Together, the study supports the social-cognitive model of the development of moral identity, according to which moral identity is based on a chronical activation of moral schemas that guide a person's perception of the social world.

Accurate Neurosurgery for the Establishment of the Electric Kindling Model of Epilepsy in Mice

This article describes in detail the essential stereotaxic neurosurgery to develop the electric experimental kindling model in mice. To date, available literature describing the methodology of the kindling model is very poor and usually neglects many relevant details about the neurosurgery, such as the manufacture of the electrodes, accurate stereotaxic coordinates of the amygdala nuclei, and the general surgery procedures (e.g., anesthesia, postsurgical recovery, fit survival of the animal’s). The electric kindling model produces a progressive development of generalized tonic-clonic seizures, which can be assessed by electroencephalography and behavioral responses. The seizures displayed are produced by a repeated low-intensity electrical stimulation in specific regions of the brain that is achieved through the previous implantation of electrodes. In this study, the aim was to implant the electrodes in basolateral amygdaloid nucleus (BLA). In order to successfully establish the kindling experimental model, neurosurgery to place the electrodes is an essential step to develop the epileptogenic phenomenon. It crucial that the surgery is carried out with exceptional exactitude, because in that way the experimental model represents an accurate and valid tool to study and understand epilepsy and the results obtained can be used to develop further strategies in epilepsy clinical research.

Human EEG recordings for 1,854 concepts presented in rapid serial visual presentation streams

The neural basis of object recognition and semantic knowledge has been extensively studied but the high dimensionality of object space makes it challenging to develop overarching theories on how the brain organises object knowledge. To help understand how the brain allows us to recognise, categorise, and represent objects and object categories, there is a growing interest in using large-scale image databases for neuroimaging experiments. In the current paper, we present THINGS-EEG, a dataset containing human electroencephalography responses from 50 subjects to 1,854 object concepts and 22,248 images in the THINGS stimulus set, a manually curated and high-quality image database that was specifically designed for studying human vision. The THINGS-EEG dataset provides neuroimaging recordings to a systematic collection of objects and concepts and can therefore support a wide array of research to understand visual object processing in the human brain.

Therapeutic Benefits of Short-Arm Human Centrifugation in Multiple Sclerosis-A New Approach.

Short-arm human centrifugation (SAHC) is proposed as a robust countermeasure to treat deconditioning and prevent progressive disability in a case of secondary progressive multiple sclerosis. Based on long-term physiological knowledge derived from space medicine and missions, artificial gravity training seems to be a promising physical rehabilitation approach toward the prevention of musculoskeletal decrement due to confinement and inactivity. So, the present study proposes a novel infrastructure based on SAHC to investigate the hypothesis that artificial gravity ameliorates the degree of disability. The patient was submitted to a 4-week training programme including three weekly sessions of 30 min of intermittent centrifugation at 1.5–2 g. During sessions, cardiovascular, muscle oxygen saturation (SmO2) and electroencephalographic (EEG) responses were monitored, whereas neurological and physical performance tests were carried out before and after the intervention. Cardiovascular parameters improved in a way reminiscent of adaptations to aerobic exercise. SmO2 decreased during sessions concomitant with increased g load, and, as training progressed, SmO2 of the suffering limb dropped, both effects suggesting increased oxygen use, similar to that seen during hard exercise. EEG showed increased slow and decreased fast brain waves, with brain reorganization/plasticity evidenced through functional connectivity alterations. Multiple-sclerosis-related disability and balance capacity also improved. Overall, this study provides novel evidence supporting SAHC as a promising therapeutic strategy in multiple sclerosis, based on mechanical loading, thereby setting the basis for future randomized controlled trials.