Changes Induced by Early Hand-Arm Bimanual Intensive Therapy Including Lower Extremities in Young Children With Unilateral Cerebral Palsy: A Randomized Clinical Trial.

Importance: Intensive interventions are provided to young children with unilateral cerebral palsy (UCP), classically focused on the upper extremity despite the frequent impairment of gross motor function. Hand-Arm Bimanual Intensive Therapy Including Lower Extremities (HABIT-ILE) effectively improves manual dexterity and gross motor function in school-aged children. Objective: To verify if HABIT-ILE would improve manual abilities in young children with UCP more than usual motor activity. Design, Setting, and Participants: This prospective randomized clinical trial (November 2018 to December 2021), including 2 parallel groups and a 1:1 allocation, recruitment took place at European university hospitals, cerebral palsy specialized centers, and spontaneous applications at 3 sites: Brussels, Belgium; Brest, France; and Pisa, Italy. Matched (age at inclusion, lesion type, cause of cerebral palsy, and affected side) pairs randomization was performed. Young children were assessed at baseline (T0), 2 weeks after baseline (T1), and 3 months after baseline (T2). Health care professionals and assessors of main outcomes were blinded to group allocation. At least 23 young children (in each group) aged 12 to 59 months with spastic/dyskinetic UCP and able to follow instructions were needed. Exclusion criteria included uncontrolled seizures, scheduled botulinum toxin injections, orthopedic surgery scheduled during the 6 months before or during the study period, severe visual/cognitive impairments, or contraindications to magnetic resonance imaging. Interventions: Two weeks of usual motor activity including usual rehabilitation (control group) vs 2 weeks (50 hours) of HABIT-ILE (HABIT-ILE group). Main Outcomes and Measures: Primary outcome: Assisting Hand Assessment (AHA); secondary outcomes: Gross Motor Function Measure-66 (GMFM-66), Pediatric Evaluation of Disability Inventory-Computer Adaptive Test (PEDI-CAT), and Canadian Occupational Performance Measure (COPM). Results: Of 50 recruited young children (26 girls [52%], median age; 35.3 months for HABIT-ILE group; median age, 32.8 months for control group), 49 were included in the final analyses. Change in AHA score from T0 to T2 was significantly greater in the HABIT-ILE group (adjusted mean score difference [MD], 5.19; 95% CI, 2.84-7.55; P < .001). Changes in GMFM-66 (MD, 4.72; 95% CI, 2.66-6.78), PEDI-CAT daily activities (MD, 1.40; 95% CI, 0.29-2.51), COPM performance (MD, 3.62; 95% CI, 2.91-4.32), and satisfaction (MD, 3.53; 95% CI, 2.70-4.36) scores were greater in the HABIT ILE group. Conclusions and Relevance: In this clinical trial, early HABIT-ILE was shown to be an effective treatment to improve motor performance in young children with UCP. Moreover, the improvements had an impact on daily life activities of these children. Trial registration: ClinicalTrials.gov Identifier: NCT04020354.

Mirror movements after bimanual intensive therapy in children with unilateral cerebral palsy: A randomized controlled trial.

AIM: To investigate potential changes in mirror movements after Hand and Arm Bimanual Intensive Therapy Including Lower Extremity (HABIT-ILE) training in children with unilateral cerebral palsy (CP). METHOD: Thirty-one children with unilateral CP (mean age 9 years 4 months, SD 4 years 3 months; range 5 years 4 months-17 years 3 months; 14 females, 17 males) were randomized to either a control or treatment group. After allocation, children were assessed three times: before (T1, baseline) and after (T2) a 2-week interval and again at 3 months after T1 (T3) as follow-up. Between T1 and T2, the treatment group received 90 hours of HABIT-ILE training, while the control group continued their customary treatment. Mirror movements were assessed in all children using the Woods and Teuber Scale, as well as the Assisting Hand Assessment, Pediatric Evaluation of Disability Inventory, and Canadian Occupational Performance Measure. RESULTS: Repeated measures analysis of variance indicated a significant decrease in mirror movements in the more-affected (mean difference = 0.97; 95% confidence interval [CI] = 0.51-1.42; p < 0.001) and less-affected (mean difference = 0.71; 95% CI = 0.37-1.0; p < 0.001) hands of children after HABIT-ILE; these improvements were maintained at the 3-month follow-up. Moreover, the mirror movement changes observed at the second assessment (T2) were inversely correlated with changes in the assessment of activities of daily living, especially in the less-affected hand. INTERPRETATION: HABIT-ILE decreased the intensity of mirror movements in a group of children with CP. Furthermore, mirror movement changes were associated with bimanual performance and activities of daily living in these children. WHAT THIS PAPER ADDS: The intensity of mirror movements decreased in both hands after 2 weeks of Hand and Arm Bimanual Intensive Therapy Including Lower Extremity (HABIT-ILE) training. Mirror movement changes were maintained at the 3-month follow-up after HABIT-ILE. Mirror movement changes were associated with improvements in bimanual performance and activities of daily living.

Protocol of changes induced by early Hand-Arm Bimanual Intensive Therapy Including Lower Extremities (e-HABIT-ILE) in pre-school children with bilateral cerebral palsy: a multisite randomized controlled trial.

BACKGROUND: Cerebral palsy (CP), which is the leading cause of motor disability during childhood, can produce sensory and cognitive impairments at different degrees. Most recent therapeutic interventions for these patients have solely focused on upper extremities (UE), although more than 60% of these patients present lower extremities (LE) deficits. Recently, a new therapeutic concept, Hand-arm Bimanual Intensive Therapy Including Lower Extremities (HABIT-ILE), has been proposed, involving the constant stimulation of UE and LE. Based on motor skill learning principles, HABIT-ILE is delivered in a day-camp setting, promoting voluntary movements for several hours per day during 10 consecutive week days. Interestingly, the effects of this intervention in a large scale of youngsters are yet to be observed. This is of interest due to the lack of knowledge on functional, neuroplastic and biomechanical changes in infants with bilateral CP. The aim of this randomized controlled study is to assess the effects of HABIT-ILE adapted for pre-school children with bilateral CP regarding functional, neuroplastic and biomechanical factors. METHODS: This international, multicentric study will include 50 pre-school children with CP from 12 to 60 months of age, comparing the effect of 50 h (2 weeks) of HABIT-ILE versus regular motor activity and/or customary rehabilitation. HABIT-ILE presents structured activities and functional tasks with continuous increase in difficulty while the child evolves. Assessments will be performed at 3 period times: baseline, two weeks later and 3 months later. The primary outcome will be the Gross Motor Function Measure 66. Secondary outcomes will include Both Hands Assessment, Melbourne Assessment-2, Semmes-Weinstein Monofilament Test, algometry assessments, executive function tests, ACTIVLIM-CP questionnaire, Pediatric Evaluation of Disability Inventory (computer adaptative test), Young Children's Participation and Environment Measure, Measure of the Process of Care, Canadian Occupational Performance Measure, neuroimaging and kinematics. DISCUSSION: The results of this study should highlight the impact of a motor, intensive, goal-directed therapy (HABIT-ILE) in pre-school children at a functional, neuroplastic and biomechanical level. In addition, this changes could demonstrated the impact of this intervention in the developmental curve of each child, improving functional ability, activity and participation in short-, mid- and long-term. NAME OF THE REGISTRY: Evaluation of Functional, Neuroplastic and Biomechanical Changes Induced by an Intensive, Playful Early-morning Treatment Including Lower Limbs (EARLY-HABIT-ILE) in Preschool Children With Uni and Bilateral Cerebral Palsy (HABIT-ILE). TRIAL REGISTRATION: NCT04017871 REGISTRATION DATE: July 12, 2019.

Habituation of phase-locked local field potentials and gamma-band oscillations recorded from the human insula.

Salient nociceptive and non-nociceptive stimuli elicit low-frequency local field potentials (LFPs) in the human insula. Nociceptive stimuli also elicit insular gamma-band oscillations (GBOs), possibly preferential for thermonociception, which have been suggested to reflect the intensity of perceived pain. To shed light on the functional significance of these two responses, we investigated whether they would be modulated by stimulation intensity and temporal expectation - two factors contributing to stimulus saliency. Insular activity was recorded from 8 depth electrodes (41 contacts) implanted in the left insula of 6 patients investigated for epilepsy. Thermonociceptive, vibrotactile, and auditory stimuli were delivered using two intensities. To investigate the effects of temporal expectation, the stimuli were delivered in trains of three identical stimuli (S1-S2-S3) separated by a constant 1-s interval. Stimulation intensity affected intensity of perception, the magnitude of low-frequency LFPs, and the magnitude of nociceptive GBOs. Stimulus repetition did not affect perception. In contrast, both low-frequency LFPs and nociceptive GBOs showed a marked habituation of the responses to S2 and S3 as compared to S1 and, hence, a dissociation with intensity of perception. Most importantly, although insular nociceptive GBOs appear to be preferential for thermonociception, they cannot be considered as a correlate of perceived pain.

Gamma-Band Oscillations Preferential for Nociception can be Recorded in the Human Insula.

Transient nociceptive stimuli elicit robust phase-locked local field potentials (LFPs) in the human insula. However, these responses are not preferential for nociception, as they are also elicited by transient non-nociceptive vibrotactile, auditory, and visual stimuli. Here, we investigated whether another feature of insular activity, namely gamma-band oscillations (GBOs), is preferentially observed in response to nociceptive stimuli. Although nociception-evoked GBOs have never been explored in the insula, previous scalp electroencephalography and magnetoencephalography studies suggest that nociceptive stimuli elicit GBOs in other areas such as the primary somatosensory and prefrontal cortices, and that this activity could be closely related to pain perception. Furthermore, tracing studies showed that the insula is a primary target of spinothalamic input. Using depth electrodes implanted in 9 patients investigated for epilepsy, we acquired insular responses to brief thermonociceptive stimuli and similarly arousing non-nociceptive vibrotactile, auditory, and visual stimuli (59 insular sites). As compared with non-nociceptive stimuli, nociceptive stimuli elicited a markedly stronger enhancement of GBOs (150-300 ms poststimulus) at all insular sites, suggesting that this feature of insular activity is preferential for thermonociception. Although this activity was also present in temporal and frontal regions, its magnitude was significantly greater in the insula as compared with these other regions.

Nociceptive Local Field Potentials Recorded from the Human Insula Are Not Specific for Nociception.

The insula, particularly its posterior portion, is often regarded as a primary cortex for pain. However, this interpretation is largely based on reverse inference, and a specific involvement of the insula in pain has never been demonstrated. Taking advantage of the high spatiotemporal resolution of direct intracerebral recordings, we investigated whether the human insula exhibits local field potentials (LFPs) specific for pain. Forty-seven insular sites were investigated. Participants received brief stimuli belonging to four different modalities (nociceptive, vibrotactile, auditory, and visual). Both nociceptive stimuli and non-nociceptive vibrotactile, auditory, and visual stimuli elicited consistent LFPs in the posterior and anterior insula, with matching spatial distributions. Furthermore, a blind source separation procedure showed that nociceptive LFPs are largely explained by multimodal neural activity also contributing to non-nociceptive LFPs. By revealing that LFPs elicited by nociceptive stimuli reflect activity unrelated to nociception and pain, our results confute the widespread assumption that these brain responses are a signature for pain perception and its modulation.

Physical factors influencing pleasant touch during passive fingertip stimulation.

OBJECTIVE: Tactile explorations with the fingertips provide information regarding the physical properties of surfaces and their relative pleasantness. Previously, we performed an investigation in the active touch domain and linked several surface properties (i.e. frictional force fluctuations and net friction) with their pleasantness levels. The aim of the present study was to investigate physical factors being important for pleasantness perception during passive fingertip stimulation. Specifically we were interested to see whether factors, such as surfaces' topographies or their frictional characteristics could influence pleasantness. Furthermore, we ascertained how the stimulus pleasantness level was impacted by (i) the normal force of stimulus application (FN) and (ii) the stimulus temperature (TS). METHODS AND RESULTS: The right index fingertips of 22 blindfolded participants were stimulated using 27 different stimuli, which varied in average roughness (Ra) and TS. A 4-axis robot moved the stimuli horizontally under participants' fingertips with three levels of FN. The robot was equipped with force sensors, which recorded the FN and friction force (FT) during stimulation. Participants rated each stimulus according to a three-level pleasantness scale, as very pleasant (scored 0), pleasant (scored 1), or unpleasant (scored 2). These ordinal pleasantness ratings were logarithmically transformed into linear and unidimensional pleasantness measures with the Rasch model. Statistical analyses were conducted to investigate a possible link between the stimulus properties (i.e. Ra, FN, FT, and TS) and their respective pleasantness levels. Only the mean Ra and FT values were negatively correlated with pleasantness. No significant correlation was detected between FN or TS and pleasantness. CONCLUSION: Pleasantness perception, resulting from passive fingertip stimulation, seems to be influenced by the surfaces' average roughness levels and average FT occurring during fingertip stimulation.

Physical factors influencing pleasant touch during tactile exploration.

BACKGROUND: When scanning surfaces, humans perceive some of their physical attributes. These percepts are frequently accompanied by a sensation of (un)pleasantness. We therefore hypothesized that aspects of the mechanical activity induced by scanning surfaces with fingertips could be objectively associated with a pleasantness sensation. Previously, we developed a unidimensional measure of pleasantness, the Pleasant Touch Scale, quantifying the pleasantness level of 37 different materials. Findings of this study suggested that the sensation of pleasantness was influenced by the average magnitude of the frictional forces brought about by sliding the finger on the surface, and by the surface topography. In the present study, we correlated (i) characteristics of the fluctuations of frictional forces resulting from the interaction between the finger and the surface asperities as well as (ii) the average friction with the sensation of pleasantness. RESULTS: Eight blindfolded participants tactually explored twelve materials of the Pleasant Touch Scale through lateral sliding movements of their index fingertip. During exploration, the normal and tangential interaction force components, fN and fT , as well as the fingertip trajectory were measured. The effect of the frictional force on pleasantness sensation was investigated through the analysis of the ratio fT to fN , i.e. the net coefficient of kinetic friction, µ. The influence of the surface topographies was investigated through analysis of rapid fT fluctuations in the spatial frequency domain. Results showed that high values of µ were anticorrelated with pleasantness. Furthermore, surfaces associated with fluctuations of fT having higher amplitudes in the low frequency range than in the high one were judged to be less pleasant than the surfaces yielding evenly distributed amplitudes throughout the whole spatial frequency domain. CONCLUSION: Characteristics of the frictional force fluctuations and of the net friction taking place during scanning can reliably be correlated with the pleasantness sensation of surfaces.

Rasch-Built Measure of Pleasant Touch through Active Fingertip Exploration.

BACKGROUND: Evidence suggests that somatic sensation has a modality for pleasant touch. OBJECTIVE: To investigate pleasant touch at the fingertip level (i.e., glabrous skin site) through the elaboration of a linear unidimensional scale that measures (i) various materials according to the level of pleasantness they elicit through active fingertip explorations and (ii) subjects according to their pleasantness leniency levels. SUBJECTS: We enrolled 198 healthy subjects without any neurological disease. METHODS: Blindfolded subjects actively explored 48 materials with their index fingertips and reported the perceived pleasantness of each on a 4-level scale. The fingertip moisture levels on each subject were measured before the experimental session. Data were analyzed using the Rasch model. RESULTS: We elaborated unidimensional linear scale that included 37 materials according to their pleasantness of touch. The pleasantness level of 21 materials was perceived differently, depending on the fingertip moisture levels of the subjects. CONCLUSION: Based on our findings, we formulated a Pleasant Touch Scale. Fingertip moisture levels appeared to be a major factor for (un)pleasant feelings during active exploration.