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Although the inhibitory action that tactile stimuli can have on pain is well documented, the precise timing of the interaction between the painful and non-painful stimuli in the central nervous system is unclear. The aim of this study was to investigate this issue by measuring the timing of the amplitude modulation of laser evoked potentials ( LEPs) due to conditioning non-painful stimuli. LEPs were recorded from 31 scalp electrodes in 10 healthy subjects after painful stimulation of the right arm (C6-C7 dermatomes). Non-painful electrical stimuli were applied by ring electrodes on the second and third finger of the right hand. Electrical stimuli were delivered at +50, +150, +200 and +250 ms interstimulus intervals ( ISIs) after the laser pulses. LEPs obtained without any conditioning stimulation were used as a baseline. As compared to the baseline, non-painful electrical stimulation reduced the amplitude of the vertex N2/P2 LEP component and the laser pain rating when electrical stimuli followed the laser pulses only at +150 and +200 ms ISIs. As at these ISIs the collision between the non-painful and painful input is likely to take place at the cortical level, we can conclude that the late processing of painful (thermal) stimuli is partially inhibited by the processing of non-painful (cutaneous) stimuli within the cerebral cortex. Moreover, our results do not provide evidence that non-painful inputs can inhibit pain at a lower level, including the spinal cord. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To investigate the possible presence of multiple spino-thalamic pathways with different conduction velocities (CVs) in the human spinal cord. Methods: Laser evoked potentials (LEPs) were recorded in 10 healthy subjects after stimulation of the dorsal midline at four vertebral level: C5, T2, T6, and T10. This method allowed us to minimize the influence of the conduction in the peripheral fibers and to calculate the spinal CV in two different ways: (1) the reciprocal of the slope of the regression line was obtained from the latencies of the different LEP components, and (2) the distance between C5 and T10 was divided by the latency difference of the responses at the two sites. In particular, we considered the middle-latency N1 potential (latencies of around 135, 150, 157, and 171ms after stimulation at C5, T2, T6, and T10 levels, respectively), which is generated in the second somatosensory (SII) area, and the late P2 response (latencies of around 336, 344, 346, and 362ms after stimulation at C5, T2, T6, and T10 levels, respectively), which is generated in the anterior cingulate cortex (ACC). Results: The calculated CV of the spinal fibers generating the N1 potential (around 9m/s) was significantly different (P <0.05) from the one of the pathway producing the P2 response (around 13m/s). Conclusions: Our results suggest that the N1 and the P2 LEP components are generated by two parallel spinal pathways. Significance: Both the N1 and P2 potentials should be recorded in the clinical routine since a dissociated abnormality of either response may be found in lesions of the nociceptive system not only in the brain, but also at spinal cord level. [Copyright &y& Elsevier]

Abstract: Previous electroencephalographic (EEG) evidence has shown event-related desynchronization (ERD) of alpha rhythms before predictable painful stimuli, as a possible neural concomitant of attentional preparatory processes (Babiloni, C., Brancucci, A., Babiloni, F., Capotosto, P., Carducci, F., Cincotti, F., Arendt-Nielsen, L., Chen, A.C., Rossini, P.M., 2003. Anticipatory cortical responses during the expectancy of a predictable painful stimulation. A high-resolution electroencephalography study. Eur. J. Neurosci. 18 (6) 1692–700). This study tested the hypothesis that alpha ERD before predictable painful stimuli is reduced as an effect of distraction. A visual warning stimulus preceded a laser painful stimulation, which was strictly followed by visual imperative stimuli. In the Pain (control) condition, no task was required after the imperative stimuli. In the Pain + Movement condition, subjects had to perform a movement of the right index finger. In the Pain + Cognition condition, they had to mentally perform an arithmetical task. EEG data were recorded in 10 subjects from 30 electrodes. Artifact-free recordings were spatially enhanced by surface Laplacian transformation. Alpha ERD was computed at three alpha sub-bands according to subjects'' individual alpha frequency peak (i.e., about 6–8 Hz, 8–10 Hz, 10–12 Hz). Compared to the control condition, the subjects reported a significantly lower stimulus intensity perception and unpleasantness in the Pain + Movement and Pain + Cognition conditions. In addition, there was a cancellation of the alpha 3 ERD (i.e., about 10–12 Hz) in Pain + Cognition condition and even a generation of a statistically significant alpha 3 ERS in Pain + Movement condition. These effects were maximum over fronto-central midline. These results suggest that distraction during the expectancy of pain is related to a reduced neural desynchronization of fronto-central midline alpha rhythms (i.e., reduced cortical activation) towards an overt hyper-synchronization (cortical idling). [Copyright &y& Elsevier]

Abstract: Objectives:: Our study aimed at investigating the effect of repetitive recordings on somatosensory evoked potentials (SEPs) related to spatial attention in a population of healthy elderly subjects. Methods:: Fifteen healthy elderly subjects were tested for six consecutive days using a somatosensory oddball paradigm, in which target stimuli were applied above the elbow and the non-target stimuli on the ipsilateral shoulder. Brain electrical activity was recorded from six scalp electrodes (Fz, Cz, F3, F4, T3 and T4). Results:: The N140 response to target stimuli showed a significantly decreased amplitude across the sessions with the lowest value during the fourth day of recording and with a partial recovery at the sixth day. On the contrary, the amplitude of the N140 response to non-target stimuli and that of the P300 potential to target stimuli were not significantly modified. Conclusions:: The significant amplitude reduction of the N140 potential in target, but not in non-target recordings across sessions, suggests that the voluntarily oriented attention is reduced by stimulus repetition, while the automatic attention is not. [Copyright &y& Elsevier]

Objective: To investigate whether the reduction of amplitude of the scalp somatosensory evoked potentials (SEPs) during movement (gating) is due to an attenuation of the afferent volley at subcortical level.Methods: Median nerve SEPs were recorded from 9 patients suffering from Parkinson''s disease, who underwent implant of intracerebral (IC) electrodes in the subthalamic nucleus or in the globus pallidum. SEPs were recorded from Erb''s point ipsilateral to stimulation, from the scalp surface and from the IC leads, at rest and during a voluntary flexo-extension movement of the stimulated wrist. The recorded IC traces were submitted to an off-line filtering by a 300–1500 bandpass to obtain the high-frequency SEP bursts.Results: IC leads recorded a triphasic component (P1–N1–P2) from 14 to 22 ms of latency. The amplitudes of the scalp N20, P20 and N30 potentials and of the IC triphasic component were significantly decreased during movement, while the peripheral N9 amplitude remained unchanged. Also the IC bursts, whose frequency was around 1000 Hz, were reduced in amplitude by the voluntary movement.Conclusions: Since the IC triphasic component is probably generated by neurons of the thalamic ventro-postero-lateral nucleus, which receive the somatosensory afferent volley, the P1–N1 amplitude reduction during movement suggests that the gating phenomenon involves also the subcortical structures. [Copyright &y& Elsevier]

Contact heat evoked potentials (CHEPs) were collected in 12 healthy subjects by stimulating the forearm skin with a couple of thermodes at a painful intensity. The stimulated area was 628 mm2 and the repetition rate was 0.1 Hz. The electroencephalogram was recorded by 31 electrodes placed on the scalp according to an extended 10–20 System. A dipolar model explaining the scalp CHEP distribution was built by using the brain electrical source analysis. The model includes two dipoles located bilaterally in the perisylvian region, one dipole in the deep midline region and two dipoles located bilaterally in the deep temporal lobe. This dipolar model is very similar to that previously described to explain the topography of evoked potentials to radiant heat stimulation by laser pulses. Since laser stimuli activate the nociceptive fibres, the strong similarity of the cerebral dipoles activated by contact heat stimuli and by laser pulses suggests that only nociceptive inputs are involved in the scalp painful CHEP building. Therefore, CHEP recording can be useful for clinical examination of the nociceptive system. [Copyright &y& Elsevier]

Background: Over the last years, the introduction of robotic technologies into Parkinson's disease rehabilitation settings has progressed from concept to reality. However, the benefit of robotic training remains elusive. This pilot randomized controlled observer trial is aimed at investigating the feasibility, the effectiveness and the efficacy of new end-effector robot training in people with mild Parkinson's disease. Methods: Design. Pilot randomized controlled trial. Setting. Robot assisted gait training (EG) compared to treadmill training (CG). Participants. Twenty cognitively intact participants with mild Parkinson's disease and gait disturbance. Interventions. The EG underwent a rehabilitation programme of robot assisted walking for 40 minutes, 5 times a week for 4 weeks. The CG received a treadmill training programme for 40 minutes, 5 times a week for 4 weeks. Main outcome measures. The outcome measure of efficacy was recorded by gait analysis laboratory. The assessments were performed at the beginning (T0) and at the end of the treatment (T1). The main outcome was the change in velocity. The feasibility of the intervention was assessed by recording exercise adherence and acceptability by specific test. Results: Robot training was feasible, acceptable, safe, and the participants completed 100% of the prescribed training sessions. A statistically significant improvement in gait index was found in favour of the EG (T0 versus T1). In particular, the statistical analysis of primary outcome (gait speed) using the Friedman test showed statistically significant improvements for the EG (p = 0,0195). The statistical analysis performed by Friedman test of Step length left (p = 0,0195) and right (p = 0,0195) and Stride length left (p = 0,0078) and right (p = 0,0195) showed a significant statistical gain. No statistically significant improvements on the CG were found. Conclusions: Robot training is a feasible and safe form of rehabilitative exercise for cognitively intact people with mild PD. This original approach can contribute to increase a short time lower limb motor recovery in idiopathic PD patients. The focus on the gait recovery is a further characteristic that makes this research relevant to clinical practice. On the whole, the simplicity of treatment, the lack of side effects, and the positive results from patients support the recommendation to extend the use of this treatment. Further investigation regarding the long-time effectiveness of robot training is warranted. Trial registration: ClinicalTrials.gov NCT01668407 [ABSTRACT FROM AUTHOR]

Abstract: Cardiac syndrome X (CSX) is characterized by effort angina, ST-segment depression during stress tests and normal coronary arteries. Abnormal nociception was suggested in these patients by studies showing a reduced cardiac pain threshold; furthermore, we recently found a lack of habituation to pain stimuli using recording of laser evoked potentials (LEPs). In CSX patients with severe angina, spinal cord stimulation (SCS) was shown to improve symptoms. In this study we investigated whether, in these patients, SCS has any effects on the excitability of the nociceptive system, assessed by LEPs recording. We studied 16 CSX patients (61.6±7 years; 4 men) who underwent SCS for refractory angina. Cortical LEPs were recorded during stimulation of the chest and right-hand during active SCS (SCS-ON) and in the absence of SCS (SCS-OFF), using a randomized cross-over design. Three sequences of painful stimuli were applied at each site during each test. During the first sequence of chest stimuli, the N2/P2 LEP amplitude was higher during the SCS-ON, compared to the SCS-OFF phase (18.2±7.8 vs. 11.5±4.4μV, P =0.006). The N2/P2 amplitude did not change significantly across the three stimulation sequences during the SCS-OFF phase (P =0.22), whereas it decreased progressively during the second and third sequence (to 87.1±29.5% and 76.4±24.1%, respectively) compared with the first sequence, during the SCS-ON phase (P =0.014). Similar results were observed during right-hand stimulation. Our study shows that in CSX patients SCS is able to restore habituation to peripheral pain stimuli. This effect might contribute to restore the ability of CSX patients to better tolerate cardiac pain. [Copyright &y& Elsevier]

Abstract: Seeing actions, emotions and feelings of other individuals may activate resonant mechanisms that allow the empathic understanding of others’ states. Being crucial for implementing pro-social behaviors, empathy is considered as inherently altruistic. Here we explored whether the personal experience of pain make individuals less inclined to share others’ pain. We used laser-evoked potentials (LEPs) to explore whether observation of painful or non-noxious stimuli delivered to a stranger model induced any modulation in the pain system of onlookers who were suffering from pain induced by the laser stimuli. After LEPs recording, participants rated intensity and unpleasantness of the laser pain, and of the pain induced by the movie in themselves and in the model. Mere observation of needles penetrating the model’s hand brought about a specific reduction of the N1/P1 LEP component, related to the activation of somatic nodes of the pain matrix. Such reduction is stronger in onlookers who rated the pain intensity induced by the pain movie as higher in themselves and lower in the model. Conversely, the N2a-P2 component, supposedly associated to affective pain qualities, did not show any specific modulation during observation of others’ pain. Thus, viewing ‘flesh and bone’ pain in others specifically modulates neural activity in the pain matrix sensory node. Moreover, this socially-derived inhibitory effect is correlated with the intensity of the pain attributed to self rather than to others suggesting that being in pain may bias the empathic relation with stranger models towards self-centred instead than other-related stances. [Copyright &y& Elsevier]

Abstract: The aim of this study was to model the cerebral generators following painful electrical stimulation of the sigmoid colon in 10 healthy controls and 10 patients with visceral pain due to the irritable bowel syndrome. The evoked brain potentials to 30 painful electrical stimuli from the sigmoid colon were recorded from 31 surface electrodes and subjected to electrical dipole source modelling. Two dipoles in the bilateral insular cortex, one dipole in the anterior cingulate gyrus and two dipoles in the bilateral second somatosensory area were found. The anterior cingulate dipole showed a more posterior position in patients than in control subjects. This finding suggests that the cortical representation of painful stimuli can be modified in presence of chronic visceral pain and that this change involves the anterior cingulate gyrus. [Copyright &y& Elsevier]

The aim of the study was to evaluate the effect of tonic pain evoked by topical application of capsaicin on the somatosensory sensation of warmth. The warmth pathways were studied in ten healthy subjects by recording the scalp potentials evoked by non-painful warm laser stimuli delivered on both the right and left perioral region (warmth C-fiber related laser-evoked potentials (C-LEPs)). Tonic pain was induced by topical capsaicin application above the lateral part of the right upper lip. The area of primary and secondary hyperalgesia were mapped. C-LEPs were obtained from 31 scalp electrodes before, during, and after capsaicin application. C-LEPs from the right perioral region were evoked by laser stimuli delivered to the area of secondary hyperalgesia during capsaicin application and on both the areas of primary and secondary hyperalgesia after capsaicin removal. While the lateralized N1/P1 component (around 185 ms of latency) was not affected by the capsaicin, the amplitudes of the later vertex C-LEPs (around 260 and 410 ms of latency for the N2a and P2 potentials, respectively) evoked from the secondary hyperalgesic area on the right side and from a symmetrical non-hyperalgesic area on the left perioral region were significantly decreased during capsaicin application and after capsaicin removal, as compared with the baseline recordings. At the same times, the rating of the laser-evoked warmth sensation was reduced significantly. This inhibitory effect can occur at brainstem level and is possibly due to: 1) trigemino-cortico-trigeminal circuits, similar to those mediating the classical diffuse noxious inhibitory control, or 2) an increased background activity of the capsaicin-insensitive A-fibers, which mediate the secondary hyperalgesia. Probably due to a peripheral inhibitory mechanism, neither reliable C-LEP components nor warmth sensation were evoked by laser pulses delivered to the primary hyperalgesic area. This is the first neurophysiological evidence in humans of an inhibitory effect of pain on warmth sensation. [ABSTRACT FROM AUTHOR]

The aim of the study was to compare the cerebral generators following painful stimulation of the sigmoid colon and the abdominal skin in 11 healthy subjects. The evoked potentials (EPs) were recorded from 31 surface electrodes following painful electrical stimuli of the sigmoid colon, and of the referred pain area on the abdomen. Current dipole models estimating the EPs amplitude and topography were calculated. For colon stimulation, the earliest cortical activities were described by dipoles in the bilateral insula and in the anterior cingulate cortex, while both secondary somatosensory areas were activated later. When the skin was stimulated, early bilateral dipoles in the primary and secondary somatosensory areas were estimated, followed by a dipole in the frontal region. This suggests that painful cutaneous and visceral stimuli are processed differently in the brain. [Copyright &y& Elsevier]

Objective: To investigate the possible contribution of the primary somatosensory area (SI) to pain sensation.Methods: Depth recordings of CO2 laser evoked potentials (LEPs) and somatosensory evoked potentials (SEPs) were performed in an epileptic patient with a stereotactically implanted electrode (Talairach coordinates y=−23, z=40) that passed about 10 mm below the hand representation in her left SI area, as assessed by the source of the N20 SEP component.Results: The intracerebral electrode was able to record the N20 SEP component after non-painful electrical stimulation of her right median nerve. The N20 potential showed a phase reversal in the bipolar montage (at about 31 mm from the midline), which confirms that the electrode was located near its generator in area 3b. In contrast, no reliable response was recorded from the SI electrode after painful CO2 laser stimulation of the right hand. An N2-P2 response was evoked at the vertex electrode (Cz), thus demonstrating the effectiveness of the delivered CO2 laser stimuli.Conclusions: Since the N20 SEP component originates from the anterior bank of the post-central gyrus (area 3b), our result suggests that this part of SI does not participate in LEP generation. In fact, the previously published LEP sources in the SI area estimated from scalp recordings are about 10–17 mm posterior of the electrode in our patient, suggesting that they are more likely located in area 1, 2 or posterior parietal cortex. [Copyright &y& Elsevier]

Objective: To investigate possible neuroplastic changes induced by pain in cerebral areas devoted to nociceptive input processing.Methods: CO2 laser-evoked potentials (LEPs) were recorded from 10 healthy subjects after stimulation of the right and left hand dorsum. Acute pain was obtained by topical application of capsaicin on the skin of right hand dorsum. LEPs were recorded after right and left hand stimulation before capsaicin, at the peak pain and 10–20 min after capsaicin removal. Right hand LEPs were evoked by laser stimuli delivered over the zone of secondary hyperalgesia during capsaicin and on both the zones of primary and secondary hyperalgesia after capsaicin removal.Results: After right hand stimulation, the vertex LEPs, which are generated in the cingulate cortex, were significantly decreased in amplitude during capsaicin application and after capsaicin removal. Moreover, the topography of these potentials was modified after capsaicin removal, shifting from the central toward the parietal region. Dipolar modelling showed that the dipolar source in the anterior cingulate cortex moved backward after capsaicin removal. All these changes were not observed after stimulation of the left hand, contralateral to the application of capsaicin, thus suggesting that functional changes are selective for the painful skin and the adjacent territories.Conclusions: Our results suggest that acute cutaneous pain may inhibit the neural activity in regions of central nervous system processing nociceptive inputs and cortical representation of these inputs can be rapidly modified in presence of acute pain. [Copyright &y& Elsevier]

Our study aimed at investigating the scalp topography of ultra-late CO2 laser evoked potentials (LEPs), which are related to C fiber activation, and at exploring the effect of attention deviation on ultra-late LEPs. Brain responses to non-painful CO2 laser stimuli were recorded in ten healthy subjects in three different conditions: (i) neutral condition in which subjects did not have any task; (ii) distraction condition in which subjects were asked to perform a mathematical task; and (iii) attention condition in which subjects had to count the number of stimuli. In all subjects, also Að fiber-related late LEPs were recorded after painful CO2 laser stimulation. The ultra-late LEPs in attention condition included an earlier negative potential (ultra-late N1) in the contralateral temporal region and a simultaneous frontal positive response (ultra-late P1). Later, a vertex biphasic component (ultra-late N2a and ultra-late P2) was identifiable. The vertex ultra-late LEP amplitude was significantly decreased in both neutral and distraction condition. Ultra-late LEPs showed a longer latency than late LEPs, but the scalp distributions of both ultra-late and late LEPs were very similar, thus suggesting that the same cerebral areas may be involved in their generation. Since attention deviations have a strong effect on ultra-late LEP amplitude, the subject''s attention should be addressed to CO2 laser stimuli when ultra-late LEPs are used for clinical purposes. [Copyright &y& Elsevier]

Supplemental digital content is available in the text. Objective: Functional outcome represents the most central objective of rehabilitation programs. Understanding which factors could affect functional status at discharge is crucial for the planning of appropriate treatments in both neurologic and orthopedic patients. The aim of this study was to investigate which clinical and demographic variables, collected at the patient's admission, could influence the functional outcome, assessed by the modified Barthel Index (mBI), at discharge. Design: A retrospective study was conducted on a large cohort (n = 3548) of orthopedic and neurologic patients. Functional, demographic, and clinical records at patient admission and mBI score at discharge were collected. General linear model analysis was performed to assess the influence of these variables on functional outcome at discharge. Results: The results reported a significant effect of mBI score at admission (P < 0.0001), age (P < 0.0001), and time from the acute event (P < 0.0001) on mBI score at discharge. Moreover, the disease type (neurologic or orthopedic) adjusted by sex (male or female) and presence of different impairments (cognitive and behavioral impairments) and complications (hypertension and cardiovascular diseases) significantly influenced mBI score at discharge (P < 0.05) (R 2 = 0.497). No significant interactions between other factors were found (P > 0.05). Conclusion: Several prognostic factors should be considered when planning an appropriate tailored rehabilitation program. [ABSTRACT FROM AUTHOR]

• Muscle ultrasound in patients with nerve trauma often identifies isles of muscle contractility when EMG is negative. • Ultrasound-guided (USG)-EMG compared to conventional needle EMG increases the specificity of motor unit potential detection. • Detection of UMG-EMG activity is a prognostic sign for partial functional recovery. To increase the specificity of motor unit potential (MUPs) detection by using ultrasound guided electromyography (USG-EMG) in patients with muscle plegia due to traumatic nerve lesions. Forty-six patients with recent nerve trauma underwent baseline standard EMG (ST-EMG) evaluation with evidence of absent MUPs. In 41 of them, ST-EMG was repeated after 2–3 months (T1) and the patients were accordingly divided in two groups: ST-EMG+ (if MUPs were detected) or ST-EMG- (MUPs not detected). Then, ST-EMG- patients underwent muscle ultrasound evaluation (M-US) and, if isles of muscular contractility were found, they also had USG-EMG. The same protocol was repeated 4–6 months after baseline (T2). At T1, 22/41 patients were ST-EMG+. While 19/41 were ST-EMG-; 9 of these patients had M-US consistent with residual muscular activity, for that reasons underwent USG-EMG with 7 of 9 demonstrating MUPs (at T2 all of these 7 patients resulted ST-EMG). In the other 2 patients, we found no MUPs at T1 but they became ST-EMG+ or USG-EMG positive at T2. The remaining 10 ST-EMG- patients had no EMG or US evidence of muscle contraction at T1, but at T2 2 of 10 became ST-EMG+ and 2 had USG-EMG showing MUPs. In the remaining 6 patients still M-US negative at T2, complete denervation was diagnosed. Concerning the 22 patients who were ST-EMG+ at T1, all but one showed increase of MUPs at T2. In this study, we demonstrated the utility of US guidance when performing EMG evaluation in locating isles of muscular contractility in patients who have no detectable MUPs on EMG after nerve trauma. USG-EMG significantly increases the specificity of needle EMG allowing earlier detection of MUPs. [ABSTRACT FROM AUTHOR]

• This randomised controlled trial compared robot-assisted gait training (RAGT) to treadmill training (TT) for people with Parkinson's disease. • RAGT and TT improved overall gait capacity to the same extent. • RAGT was more effective than TT in improving freezing of gait (FOG). • RAGT reduced FOG more in dependent walkers than independent walkers. • Disability level was reduced in freezers more than in non-freezers. Although gait disorders strongly contribute to perceived disability in people with Parkinson's disease, clinical trials have failed to identify which task-oriented gait training method can provide the best benefit. Freezing of gait remains one of the least investigated and most troublesome symptoms. We aimed to compare the effects of robot-assisted gait training and treadmill training on endurance and gait capacity in people with Parkinson disease; the secondary aim was to compare the effect of the treatments in people with freezing and/or severe gait disability and assess changes in overall disease-related disability and quality of life. Outpatients with Parkinson disease (Hoehn and Yahr stage ≥ 2) were randomly assigned to receive 20 sessions of 45-min gait training assisted by an end-effector robotic device (G-EO System) or treadmill training. Outcome assessments were the 6-min walk test, Timed Up and Go test, Freezing of Gait Questionnaire, Unified Parkinson's Disease Rating Scales and Parkinson's Disease Quality of Life Questionnaire-39 administered before (T0) and after treatment (T1). We included 96 individuals with Parkinson disease: 48 with robot-assisted gait training and 48 treadmill training. Both groups showed significant improvement in all outcomes. As compared with baseline, with robot-assisted gait training and treadmill training, endurance and gait capacity were enhanced by 18% and 12%, respectively, and motor symptoms and quality of life were improved by 17% and 15%. The maximum advantage was observed with the Freezing of Gait Questionnaire score, which decreased by 20% after either treatment. On post-hoc analysis, dependent walkers benefited more than independent walkers from any gait training, whereas freezers gained more from robot-assisted than treadmill training in terms of freezing reduction. Repetitive intensive gait training is an effective treatment for people with Parkinson disease and can increase endurance and gait velocity, especially for those with severe walking disability. Advantages are greater with robot-assisted gait training than treadmill training for individuals with freezing of gait – related disability. [ABSTRACT FROM AUTHOR]

• Virtual reality (VR) and serious games (SGs) are widely used in rehabilitation. • VR-based SG balance training and conventional therapy showed similar outcomes. • VR-based SG static balance training seemed to elicit a better gait pattern than conventional therapy. • VR-based SG statistic balance training was safe and well tolerated. • VR-based SG balance training can be used to intensify the rehabilitation treatment. Virtual reality (VR) and serious games (SGs) are widespread in rehabilitation for many orthopedic and neurological diseases. However, few studies have addressed the effects of rehabilitation with VR-based SGs on clinical, gait, and postural outcomes in individuals with total knee replacement (TKR). The primary objective was the efficacy of balance training using non-immersive VR-based SGs compared to conventional therapy in TKR patients on the Time Up and Go test. Secondary objectives included the efficacy on clinical, gait, and postural outcomes. We randomly allocated 56 individuals with unilateral TKR to the experimental group (EG) or control group (CG) for 15 sessions (45 min; 5 times per week) of non-immersive VR-based SGs or conventional balance training, respectively. The primary outcome was functional mobility measured by the Timed Up and Go test; secondary outcomes were walking speed, pain intensity, lower-limb muscular strength, independence in activities of daily living as well as gait and postural parameters. We found significant within-group differences in all clinical outcomes and in a subset of gait (p <0.0001) and postural (p ≤ 0.05) parameters. Analysis of the stance time of the affected limb revealed significant between-group differences (p = 0.022): post-hoc analysis revealed within-group differences in the EG (p = 0.002) but not CG (p = 0.834). We found no significant between-group differences in other outcomes. Balance training with non-immersive VR-based SGs can improve clinical, gait, and postural outcomes in TKR patients. It was not superior to the CG findings but could be considered an alternative to the conventional approach and can be added to a regular rehabilitation program in TKR patients. The EG had a more physiological duration of the gait stance phase at the end of the treatment than the CG. NCT03454256 [ABSTRACT FROM AUTHOR]

Background: Over the last years, the introduction of robotic technologies into Parkinson's disease rehabilitation settings has progressed from concept to reality. However, the benefit of robotic training remains elusive. This pilot randomized controlled observer trial is aimed at investigating the feasibility, the effectiveness and the efficacy of new end-effector robot training in people with mild Parkinson's disease.Methods: Design. Pilot randomized controlled trial.Results: Robot training was feasible, acceptable, safe, and the participants completed 100% of the prescribed training sessions. A statistically significant improvement in gait index was found in favour of the EG (T0 versus T1). In particular, the statistical analysis of primary outcome (gait speed) using the Friedman test showed statistically significant improvements for the EG (p = 0,0195). The statistical analysis performed by Friedman test of Step length left (p = 0,0195) and right (p = 0,0195) and Stride length left (p = 0,0078) and right (p = 0,0195) showed a significant statistical gain. No statistically significant improvements on the CG were found.Conclusions: Robot training is a feasible and safe form of rehabilitative exercise for cognitively intact people with mild PD. This original approach can contribute to increase a short time lower limb motor recovery in idiopathic PD patients. The focus on the gait recovery is a further characteristic that makes this research relevant to clinical practice. On the whole, the simplicity of treatment, the lack of side effects, and the positive results from patients support the recommendation to extend the use of this treatment. Further investigation regarding the long-time effectiveness of robot training is warranted.Trial Registration: ClinicalTrials.gov NCT01668407. [ABSTRACT FROM AUTHOR]

( Headache 2012;52:792-807) Objective.- Our aim was to investigate CO2 laser-evoked potential (LEP) habituation to experimental pain in a group of patients affected by medication-overuse headache, with a history of episodic migraine becoming chronic, before and after treatment, consisting in acute medication withdrawal and a preventive treatment cycle. Background.- One of the main features of LEPs in migraineurs is a lower habituation to repetitive noxious stimuli during the interictal phase. Methods.- LEPs were recorded to stimulation of both the right hand and the right perioral region in 14 patients and in 14 healthy subjects. The habituation of both the N1 and the vertex N2/P2 components was assessed by measuring the LEP amplitude changes across 3 consecutive repetitions of 30 trials each. Results.- In the 8 patients who had clinically improved after treatment, the N2/P2 amplitude habituation was significantly higher after treatment than before treatment following both hand ( F = 43.2, P < .0001) and face stimulation ( F = 6.9, P = .01). In these patients, the N2/P2 amplitude habituation after treatment was not different from that obtained in healthy controls ( P = .18 and P = .73 for hand and face stimulation, respectively). On the contrary, in the patients who did not improve, the N2/P2 amplitude still showed reduced habituation after both hand ( F = 3.1, P = .08) and face ( F = 0.7, P = .4) stimulation. Conclusion.- The deficient habituation of the vertex N2/P2 complex was partly restored after successful treatment of medication-overuse headache, reflecting a modification in pain-processing pathways. [ABSTRACT FROM AUTHOR]

Abstract: Charcot-Marie-Tooth (CMT) disease is the most common inherited neuropathy. The CMT1A type can be considered the typical phenotype of this disease. Although pain is not considered a relevant symptom in CMT patients by physicians and no study assessed it comprehensively, this symptom is frequently complained by patients. The objective of the present study was to investigate the nociceptive system in a sample of CMT1A patients suffering from pain by laser-evoked potentials (LEPs). Moreover, we also used a pain specific questionnaire in order to obtain patient-oriented data about their painful symptoms, the Neuropathic Pain Diagnostic Questionnaire (DN4). We evaluated 16 patients affected by CMT1A and 14 controls. All subjects underwent a standard LEP recording session (foot, hand, and face stimulation) and filled in the DN4. While the N2/P2 amplitude to foot stimulation was lower in CMT patients than in controls (p =0.003), no difference in LEP amplitude to both hand and face stimulation was found between patients and healthy subjects (p >0.05). This result is probably due to a length-dependent Aδ-fiber loss which involves mostly the longer fibers coming from the lower limb. In our patients, there was a significant association between a reduced N2/P2 amplitude to foot stimulation and a high DN4 score (p =0.03), meaning that patients with highly probable neuropathic pain had also low N2/P2 amplitude values to painful foot stimulation. This suggests that in our CMT1A patients neuropathic pain is probably related to a reduction of the Aδ afferents. [Copyright &y& Elsevier]

Abstract: Expectation and conditioning are supposed to be the two main psychological mechanisms for inducing a placebo response. Here, we further investigate the effects of both expectation, which was induced by verbal suggestion alone, and conditioning at the level of N1 and N2–P2 components of CO2 laser-evoked potentials (LEPs) and subjective pain reports. Forty-four healthy volunteers were pseudorandomly assigned to one of three experimental groups: Group 1 was tested with verbal suggestion alone, Group 2 was tested with a conditioning procedure, whereby the intensity of painful stimulation was reduced surreptitiously, so as to make the volunteers believe that the treatment was effective, Group 3 was a control group that allowed us to rule out phenomena of sensitization and/or habituation. Pain perception was assessed according to a Numerical Rating Scale (NRS) ranging from 0=no pain sensation to 10=maximum imaginable pain. Both verbal suggestions (Group 1) and conditioning (Group 2) modified the N2–P2 complex, but not the N1 component of LEPs. However, the suggestion-induced LEP changes occurred without subjective perception of pain decrease. Conversely, the N2–P2 amplitude changes that were induced by the conditioning procedure were associated with the subjective perception of pain reduction. Compared to natural history, conditioning produced more robust reductions of LEP amplitudes than verbal suggestions alone. Overall, these findings indicate that prior positive experience plays a key role in maximizing both behavioral and neurophysiological placebo responses, emphasizing that the placebo effect is a learning phenomenon which affects the early central nociceptive processing. [Copyright &y& Elsevier]

Abstract: Since a number of patients with Parkinson’s Disease (PD) complain of painful sensations, we studied whether the central processing of nociceptive inputs is abnormal in PD. To test this hypothesis, we recorded scalp CO2 laser evoked potentials (LEPs) to hand skin stimulation in 18 pain-free PD patients with unilateral bradykinetic-rigid syndrome (hemiparkinson) during the off state and in 18 healthy subjects. This technique allows us to explore non-invasively the functional status of some cerebral structures involved in nociceptive input processing. In both PD patients and control subjects, CO2 laser stimulation gave rise to a main negative N2 potential followed by a positive P2 response at vertex peaking at a latency of about 200 and 300ms, respectively. These potentials are thought to originate from several brain structures devoted to nociceptive input processing, including the cingulate gyrus and insula. PD patients and normal subjects showed comparable N2 and P2 latencies, whereas the N2/P2 peak-to-peak amplitude was significantly lower in PD patients (regardless of the clinically affected body side) than in controls. LEPs were even recorded after acute L-dopa administration in 7 additional PD patients. L-dopa administration yielded no significant change in N2/P2 amplitude as compared to the off state. These results suggest an abnormal nociceptive input processing in pain-free PD patients which appears to be independent of clinical expression of parkinsonian motor signs and is not affected by dopaminergic stimulation. [Copyright &y& Elsevier]

Abstract: It is well known that scalp potentials evoked by nonpainful visual and auditory stimuli are enhanced in amplitude when preceded by pre-stimulus low-amplitude alpha rhythms. This study tested the hypothesis that the same holds for the amplitude of vertex N2–P2 potentials evoked by brief noxious laser stimuli, an issue of interest for clinical perspective. EEG data were recorded in 10 subjects from 30 electrodes during laser noxious stimulation. The artifact-free vertex N2–P2 complex was spatially enhanced by surface Laplacian transformation. Pre-stimulus alpha power was computed at three alpha sub-bands according to subject''s individual alpha frequency peak (i.e. about 6–8Hz for alpha 1, 8–10Hz for alpha 2 and 10–12Hz for alpha 3 sub-band). Individual EEG single trials were divided in two sub-groups. The strong-alpha sub-group (high band power) included halfway of all EEG single trials, namely those having the highest pre-stimulus alpha power. Weak-alpha sub-group (low band power) included the remaining trials. Averaging procedure provided laser evoked potentials for both trial sub-groups. No significant effect was found for alpha 1 and alpha 2 sub-bands. Conversely, compared to strong-alpha 3 sub-group, weak-alpha 3 sub-group showed vertex N2–P2 potentials having significantly higher amplitude (p <0.05). These results extend to the later phases of pain processing systems the notion that generation mechanisms of pre-stimulus alpha rhythms and (laser) evoked potentials are intrinsically related and subjected to fluctuating “noise”. That “noise” could explain the trial-by-trial variability of laser evoked potentials and perception. [Copyright &y& Elsevier]

Abstract: Our study aimed at investigating the nociceptive contribution to the somatosensory evoked potentials after electrical intramuscular stimulation (mSEPs) at painful intensity. Scalp mSEPs were recorded in 10 healthy subjects after electrical stimulation of the left brachioradialis muscle at three intensities: non-painful (I2), slightly painful (I4) and moderately painful (I6). For each intensity, mSEPs were recorded in a neutral condition (NC) in which subjects did not have any task, and in an attention condition (AC) in which subjects were asked to count the number of stimuli. In both NC and AC, the N120 and P220 amplitudes were significantly higher at I6 than at I2. While the N120 amplitude did not vary between NC and AC, the P220 amplitude was significantly higher in AC than in NC at all stimulus intensities. Our results suggest that nociceptive inputs contribute to the N120 amplitude increase at painful stimulus intensity, while the P220 amplitude is more sensitive to changes of subjects’ attention level. Therefore, the N120 amplitude increase to moderately painful stimuli, as compared to non-painful stimuli, may represent a marker of the activation of the muscular thin myelinated afferents. [Copyright &y& Elsevier]

The oesophagus, stomach, duodenum and sigmoid colon were electrically stimulated in 12 healthy volunteers with a thin nasal endoscope. The painful cortical evoked potentials (EPs) were recorded from 64 surface electrodes. The early EPs with latencies < 200 ms were studied and the corresponding dipole sources were calculated. The electrical current intensities needed to evoke pain were highest in the stomach and duodenum, compared to the other segments ( F = 7.8; P < 0.001; post hoc analysis P < 0.05). The EP latencies after stimulation of the stomach and sigmoid colon were shorter compared with those to stimulation of the oesophagus and duodenum (all P values < 0.001). The EP amplitudes were higher to oesophagus stimulation (all P values < 0.001 except for the early positivity). The potential fields obtained after stimulation of the most distal segments (duodenum and sigmoid colon) were in general distributed more posteriorly compared to those recorded in the more proximal regions. The EP topographies to stimulation of all gut tracts were explained by a bilateral source in the second somatosensory (SII) area, by a dipole in the anterior cingulate cortex (ACC), and by a bilateral generator in the insular cortex. However, the position of the sources significantly changed depending on the stimulated gut tract. Moreover, while the SII and ACC sources were initially activated to oesophagus and stomach stimulation, the ACC and insular activities were the earliest ones after stimulation of the lower gut segments. The findings reflect differences in pathways and brain processing of visceral nociceptive inputs coming from either upper or lower gut and may improve our understanding of the brain-gut axis in health and disease. [ABSTRACT FROM AUTHOR]

Objective: To study whether sensorimotor cortical areas are involved in Essential Tremor (ET) generation.Background: It has been suggested that sensorimotor cortical areas can play a role in ET generation. Therefore, we studied median nerve somatosensory evoked potentials (SEPs) in 10 patients with definite ET.Methods: To distinguish SEP changes due to hand movements from those specifically related to central mechanisms of tremor, SEPs were recorded at rest, during postural tremor and during active and passive movement of the hand. Moreover, we recorded SEPs from 5 volunteers who mimicked hand tremor. The traces were further submitted to dipolar source analysis.Results: Mimicked tremor in controls as well as active and passive hand movements in ET patients caused a marked attenuation of all scalp SEP components. These SEP changes can be explained by the interference between movement and somatosensory input (‘gating’ phenomenon). By contrast, SEPs during postural tremor in ET patients showed a reduction of N20, P22, N24 and P24 cortical SEP components, whereas the fronto-central N30 wave remained unaffected.Conclusions: Our findings suggest that in ET patients the physiological interference between movement and somatosensory input to the cortex is not effective on the N30 response. This finding thus indicates that a dysfunction of the cortical generator of the N30 response may play a role in the pathogenesis of ET. [Copyright &y& Elsevier]

Background: Overground Robot-Assisted Gait Training (o-RAGT) provides intensive gait rehabilitation. This study investigated the efficacy of o-RAGT in subacute stroke subjects, compared to conventional gait training. Methods: A multicenter randomized controlled trial was conducted on 75 subacute stroke subjects (38 in the Experimental Group (EG) and 37 in the Control Group (CG)). Both groups received 15 sessions of gait training (5 sessions/week for 60 min) and daily conventional rehabilitation. The subjects were assessed at the beginning (T1) and end (T2) of the training period with the primary outcome of a 6 Minutes Walking Test (6MWT), the Modified Ashworth Scale of the Affected lower Limb (MAS-AL), the Motricity Index of the Affected lower Limb (MI-AL), the Trunk Control Test (TCT), Functional Ambulation Classification (FAC), a 10 Meters Walking Test (10MWT), the modified Barthel Index (mBI), and the Walking Handicap Scale (WHS). Results: The 6MWT increased in both groups, which was confirmed by both frequentist and Bayesian analyses. Similar outcomes were registered in the MI-AL, 10MWT, mBI, and MAS-AL. The FAC and WHS showed a significant number of subjects improving in functional and community ambulation in both groups at T2. Conclusions: The clinical effects of o-RAGT were similar to conventional gait training in subacute stroke subjects. The results obtained in this study are encouraging and suggest future clinical trials on the topic. [ABSTRACT FROM AUTHOR]