Background. Brain-machine interfaces (BMIs) have been recently proposed as a new tool to induce functional recovery in stroke patients. Objective. Here we evaluated long-term effects of BMI training and physiotherapy in motor function of severely paralyzed chronic stroke patients 6 months after intervention. Methods. A total of 30 chronic stroke patients with severe hand paresis from our previous study were invited, and 28 underwent follow-up assessments. BMI training included voluntary desynchronization of ipsilesional EEG-sensorimotor rhythms triggering paretic upper-limb movements via robotic orthoses (experimental group, n = 16) or random orthoses movements (sham group, n = 12). Both groups received identical physiotherapy following BMI sessions and a home-based training program after intervention. Upper-limb motor assessment scores, electromyography (EMG), and functional magnetic resonance imaging (fMRI) were assessed before (Pre), immediately after (Post1), and 6 months after intervention (Post2). Results. The experimental group presented with upper-limb Fugl-Meyer assessment (cFMA) scores significantly higher in Post2 (13.44 ± 1.96) as compared with the Pre session (11.16 ± 1.73; P = .015) and no significant changes between Post1 and Post2 sessions. The Sham group showed no significant changes on cFMA scores. Ashworth scores and EMG activity in both groups increased from Post1 to Post2. Moreover, fMRI-BOLD laterality index showed no significant difference from Pre or Post1 to Post2 sessions. Conclusions. BMI-based rehabilitation promotes long-lasting improvements in motor function of chronic stroke patients with severe paresis and represents a promising strategy in severe stroke neurorehabilitation.

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. A widely accepted notion is that the insula, especially its posterior portion, plays a specific role in the perception of pain. This has led a number of researchers to consider activity recorded from this so-called “ouch zone” as an objective correlate of pain perception. We provide compelling evidence to the contrary. Using direct intracerebral recordings, we demonstrate that painful and nonpainful stimuli elicit very similar responses throughout the human insula. This observation argues against the notion that these responses reflect the brain activity through which pain emerges from nociception in the human brain. These findings have implications for basic theories, as well as for the development of diagnostic tests and the identification of therapeutic targets for the treatment of chronic pain. They question the use of these insular responses to assess the effects of pharmacological treatment or to assess pain in patients unable to communicate. Furthermore, they have legal implications, as they contradict the proposal that these responses could be used to determine unequivocally whether plaintiffs are truly experiencing the pain for which they are seeking redress. Finally, they undermine the rationale for neurosurgical procedures aiming at alleviating pain by targeting the posterior 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.