Clinical Research Directory

Immersive AOT: Multisensory Stimulation and Neurophysiological Correlates in Children With Cerebral Palsy and Typical Development - A Pilot Study

The discovery of the Mirror Neuron System (MNS) has promoted the development of rehabilitation techniques such as Action Observation Treatment (AOT) and Motor Imagery (MI). These are based on the principle that neural circuits active during execution, also activate during the observation or imagination of movements. These techniques have been found to be effective in several clinical populations including children with Cerebral Palsy (CP), the most common childhood-onset motor disorder. We hypothesize that a multimodal version of AOT, integrating not only visual stimuli (standard practice) but also auditory and tactile stimuli, could further enhance the activation of the MNS. In fact, everyday actions naturally involve multiple sensory channels, and evidence indicate that audio-visual action observation activates the MNS more intensely than visual stimuli alone, thus offering a potential improvement for CP rehabilitation. The primary aim of this observational pilot study, conducted at IRCCS Fondazione Stella Maris, is to verify whether a multisensory (=immersive) AO session - combining visual, auditory, and tactile stimuli - produces greater activation of the MNS, than a traditional session (visual AO alone). Neural correlates will be measured through high-density Electroencephalography (hdEEG), with a specific focus on the modulation of the sensorimotor mu rhythm. Twenty children and adolescents with CP, aged 7-25 years, and 20 typically developing (TD) aged-matched peers will be recruited in the study. The study also aims to assess the level of participants' attention during stimuli presentation through eye tracking, and to verify whether immersive AO can influence MI abilities, measured through specific tasks and questionnaires (i.e., Motor Imagery Questionnaire for Children (MIQ-C, aged 7-12) and the Motor Imagery Questionnaire - 3 (MIQ-3) for adolescent). In an initial phase of the study both questionnaires will be the validated in a separate sample of 120 TD Italian children and 120 Italian adolescents or adults. The absence of intellectual disability will be assessed using the age-appropriate version of Raven's Progressive Matrices test. Each participant will undergo two EEG sessions: the immersive session will consist of watching first-person videos accompanied by auditory stimuli consistent with the action and tactile stimuli provided by TouchDIVER Pro haptic gloves (Weart, CE-marked device), suitably adapted for the paediatric population. The traditional session will consist of watching videos without sounds or any tactile additional stimulus. The two sessions will be performed in a in random order. In both sessions, after the observation phase, participants will be asked to perform or imagine the same actions presented in the videos. During observation, eye movements and gaze behavior will be monitored using an eye tracking system. Throughout each session, cortical activity will be recorded using a 128-channel hdEEG net. The sessions will be video-recorded to accurately monitor participants motor behavior, response times, and compliance with the protocol. At the end of each EEG session, participants will be administered the MIQ-C or MIQ-3 questionnaire and a short task to assess MI abilities. In this task, participants will watch some of the videos previously used during the EEG session and will then be asked to imagine the same action. In this case, their imagery will be interrupted at specific time points, and they will be asked to select, from two images, the moment of the action corresponding to the point at which they were interrupted. Data analysis will examine within- and between-groups differences for the immersive AO vs the traditional AO. Correlation analysis will be also performed between neurophysiological data, attentional data, questionnaires, MI responses and standardized clinical assessments ( for the CP group), in order to understand how the participants' motor and cognitive abilities influence the activation of the circuits involved in the experimental tasks.

Neural Correlates of Goal-directed Action Observation and Execution in Children With Unilateral Cerebral Palsy

Cerebral palsy (CP) is the most common childhood-onset motor disorder, with Unilateral Cerebral Palsy (UCP)- motor impairment predominantly impacting one side of the body-representing the most frequent form of CP. Among available rehabilitation programs, Action Observation Treatment (AOT) has gained increasing attention for its demonstrated effectiveness in improving manual motor function. AOT involves the systematic observation of goal-directed actions followed by their execution/imitation and is thought to leverage the mirror mechanism and its role in motor learning. Specifically, it relies on the neurophysiological principle that observing others' actions activates the same neural structures involved in executing those actions, reflecting the engagement of the mirror neuron system (MNS). In children with CP, the feasibility and effectiveness of AOT have been shown functionally (Sgandurra et al., 2013, Buchignani et al., 2019). However, despite its theoretical grounding in MNS functioning, the neurophysiological correlates of this system in children with CP remain less characterized, with only limited investigations using functional neuroimaging (e.g., Sgandurra et al., 2020) or neurophysiological methods such as electroencephalography (EEG; e.g., Demas et al., 2019). This observational study aims to characterize the neurophysiological signatures of action execution and action observation in children aged 5-15 years with a diagnosis of UCP compared to a group of age-matched typically developing (TD) peers. To this end, non-invasive high-density EEG (hdEEG) will be used to quantify sensorimotor cortex modulation through mu-rhythm reactivity-specifically event-related desynchronization (ERD) and synchronization (ERS)-and its topographical distribution during an active visuo-motor task involving upper limbs. Mu-rhythm desynchronization (or suppression) over sensorimotor regions is a well-established marker of MNS engagement. A secondary objective is to examine the relationship between EEG measures and participants' attention, upper-limb kinematics, and manual motor function. To this purpose, participants will wear non-invasive wearable sensors to capture arm/hand kinematics, and attention will be monitored with a non-invasive eye-tracking system. Validated scales will be used to assess manual motor function. Participants will take part in one single visit of about 1.5 hours. During the EEG acquisition session, children will wear a 128-channel EEG net and complete an active visuo-motor paradigm including the observation and execution of unimanual and bimanual goal-directed actions (e.g., reaching-grasping). In the observation condition, children will watch videos depicting these actions on a computer screen while refraining from movement. In the subsequent execution condition, they will interact themselves with the same objects as in the observation condition. Throughout the same session, children's attention/gaze will be tracked via eye-tracking, and upper-limb kinematics will be recorded using wearable inertial measurement unit (IMU) sensors. Before or after EEG acquisition, manual motor function will be assessed using two standardized scales: the Assisting Hand Assessment (AHA) and the Melbourne Assessment-2 (MA-2). Data analysis will characterize the mu rhythm ERD topography and temporal dynamics during both action execution and action observation, within and between groups. Correlation analyses will explore associations between neurophysiological measures, gaze and attentional patterns, kinematic data, and motor assessments scores to elucidate how motor and attentional factors modulate sensorimotor cortical activation.