The analgesic power of pleasant touch in individuals with chronic pain: Recent findings and new insights.

This mini-review covers recent works on the study of pleasant touch in patients with chronic pain (CP) and its potential use as a treatment. While experiments have demonstrated that pleasant touch, through the activation of CT-afferents and the brain regions involved in its affective value, might reduce the unpleasantness and intensity of induced pain, the interaction between pleasant touch and CP remains under-examined. Some experiments show that CP might disrupt the positive aspects of receiving pleasant touch, while in other studies the perception of pleasantness is preserved. Moreover, only a few attempts have been made to test whether touch can have a modulatory effect on CP, but these results also remain inconclusive. Indeed, while one recent study demonstrated that CT-touch can diminish CP after a short stimulation, another study suggested that pleasant touch might not be sufficient. Future studies should further investigate the psychological and neural interplay between pleasant touch and CP. In the conclusion of this mini-review, we propose a new tool we have recently developed using immersive virtual reality (IVR).

Movement vigor: Frameworks, exceptions, and nomenclature.

Shadmehr and Ahmed cogently argue that vigor of appetitive movements is positively correlated with their value, and that value can therefore be inferred by measuring vigor. Here, we highlight three points to consider when interpreting this account: (1) The correlation between vigor and value is not obligatory, (2) the vigor effect also arises in frameworks other than optimal foraging, and (3) the term vigor can be misinterpreted, thereby affecting rigor.

Percutaneous microwave ablation of renal masses in a UK cohort.

OBJECTIVES: To report a tertiary referral centre's experience of microwave ablation (MWA) for suspected renal cell carcinoma (RCC), describing complications and oncological outcomes. PATIENTS AND METHODS: Consecutive MWA procedures (n = 113) for renal masses (October 2016 to September 2019) were maintained on a prospective database. Data describing patient, disease, procedure, complications, and oncological outcomes were analysed. RESULTS: The median (range) age was 68 (33-85) years, 73% were male, and the median Charlson Comorbidity Index was 0. The median (interquartile range [IQR]) tumour diameter was 25 (20-32) mm. In all, 95% had renal mass biopsy, with histologically confirmed cancer in 75%. The median (IQR) R.E.N.A.L. (Radius, Exophytic/Endophytic, Nearness, Anterior/Posterior, Location) nephrometry score was 7 (6-8). The median ablation time was 6 min and length of stay was 1 day for 95% of the patients. Clavien-Dindo complication Grades I, II, IIIb and IV occurred in 18%, 1.8%, 0.9% and 0.9%, respectively. The median follow-up was 12 months and the median (IQR) renal function change was -4 (-18 to 0)%. One patient (0.9%) had local recurrence, treated with re-ablation; two developed metastatic progression; and two (1.8%) had indeterminate findings on follow-up (one lung nodule and one possible local recurrence), managed with ongoing protocolised computed tomography surveillance. Post-procedure complications were associated with total ablation time (odds ratio [OR] 1.152/min, 95% confidence interval [CI] 1.040-1.277) and total ablation energy (OR 1.017/kJ, 95% CI 1.001-1.033). CONCLUSIONS: We describe the largest UK series of MWA treatment for T1a/small T1b renal masses to date. MWA was well tolerated, with 95% discharged the following day and low complication/re-admission rates. Current follow-up demonstrates favourable disease control. MWA appears to be safe and effective and should be considered in future prospective comparisons of treatments for T1a/small T1b renal masses.

Ultralow-frequency neural entrainment to pain.

Nervous systems exploit regularities in the sensory environment to predict sensory input, adjust behavior, and thereby maximize fitness. Entrainment of neural oscillations allows retaining temporal regularities of sensory information, a prerequisite for prediction. Entrainment has been extensively described at the frequencies of periodic inputs most commonly present in visual and auditory landscapes (e.g., >0.5 Hz). An open question is whether neural entrainment also occurs for regularities at much longer timescales. Here, we exploited the fact that the temporal dynamics of thermal stimuli in natural environment can unfold very slowly. We show that ultralow-frequency neural oscillations preserved a long-lasting trace of sensory information through neural entrainment to periodic thermo-nociceptive input as low as 0.1 Hz. Importantly, revealing the functional significance of this phenomenon, both power and phase of the entrainment predicted individual pain sensitivity. In contrast, periodic auditory input at the same ultralow frequency did not entrain ultralow-frequency oscillations. These results demonstrate that a functionally significant neural entrainment can occur at temporal scales far longer than those commonly explored. The non-supramodal nature of our results suggests that ultralow-frequency entrainment might be tuned to the temporal scale of the statistical regularities characteristic of different sensory modalities.

The effect of salient stimuli on neural oscillations, isometric force, and their coupling.

Survival in a suddenly-changing environment requires animals not only to detect salient stimuli, but also to promptly respond to them by initiating or revising ongoing motor processes. We recently discovered that the large vertex brain potentials elicited by sudden supramodal stimuli are strongly coupled with a multiphasic modulation of isometric force, a phenomenon that we named cortico-muscular resonance (CMR). Here, we extend our investigation of the CMR to the time-frequency domain. We show that (i) both somatosensory and auditory stimuli evoke a number of phase-locked and non-phase-locked modulations of EEG spectral power. Remarkably, (ii) some of these phase-locked and non-phase-locked modulations are also present in the Force spectral power. Finally, (iii) EEG and Force time-frequency responses are correlated in two distinct regions of the power spectrum. An early, low-frequency region (∼4 Hz) reflects the previously-described coupling between the phase-locked EEG vertex potential and force modulations. A late, higher-frequency region (beta-band, ∼20 Hz) reflects a second coupling between the non-phase-locked increase of power observed in both EEG and Force. In both time-frequency regions, coupling was maximal over the sensorimotor cortex contralateral to the hand exerting the force, suggesting an effect of the stimuli on the tonic corticospinal drive. Thus, stimulus-induced CMR occurs across at least two different types of cortical activities, whose functional significance in relation to the motor system should be investigated further. We propose that these different types of corticomuscular coupling are important to alter motor behaviour in response to salient environmental events.

An Action Field Theory of Peripersonal Space.

Predominant conceptual frameworks often describe peripersonal space (PPS) as a single, distance-based, in-or-out zone within which stimuli elicit enhanced neural and behavioural responses. Here we argue that this intuitive framework is contradicted by neurophysiological and behavioural data. First, PPS-related measures are not binary, but graded with proximity. Second, they are strongly influenced by factors other than proximity, such as walking, tool use, stimulus valence, and social cues. Third, many different PPS-related responses exist, and each can be used to describe a different space. Here, we reconceptualise PPS as a set of graded fields describing behavioural relevance of actions aiming to create or avoid contact between objects and the body. This reconceptualisation incorporates PPS into mainstream theories of action selection and behaviour.

Saliency Detection as a Reactive Process: Unexpected Sensory Events Evoke Corticomuscular Coupling.

Survival in a fast-changing environment requires animals not only to detect unexpected sensory events, but also to react. In humans, these salient sensory events generate large electrocortical responses, which have been traditionally interpreted within the sensory domain. Here we describe a basic physiological mechanism coupling saliency-related cortical responses with motor output. In four experiments conducted on 70 healthy participants, we show that salient substartle sensory stimuli modulate isometric force exertion by human participants, and that this modulation is tightly coupled with electrocortical activity elicited by the same stimuli. We obtained four main results. First, the force modulation follows a complex triphasic pattern consisting of alternating decreases and increases of force, time-locked to stimulus onset. Second, this modulation occurs regardless of the sensory modality of the eliciting stimulus. Third, the magnitude of the force modulation is predicted by the amplitude of the electrocortical activity elicited by the same stimuli. Fourth, both neural and motor effects are not reflexive but depend on contextual factors. Together, these results indicate that sudden environmental stimuli have an immediate effect on motor processing, through a tight corticomuscular coupling. These observations suggest that saliency detection is not merely perceptive but reactive, preparing the animal for subsequent appropriate actions.SIGNIFICANCE STATEMENT Salient events occurring in the environment, regardless of their modalities, elicit large electrical brain responses, dominated by a widespread "vertex" negative-positive potential. This response is the largest synchronization of neural activity that can be recorded from a healthy human being. Current interpretations assume that this vertex potential reflects sensory processes. Contrary to this general assumption, we show that the vertex potential is strongly coupled with a modulation of muscular activity that follows the same pattern. Both the vertex potential and its motor effects are not reflexive but strongly depend on contextual factors. These results reconceptualize the significance of these evoked electrocortical responses, suggesting that saliency detection is not merely perceptive but reactive, preparing the animal for subsequent appropriate actions.

Gravitational cues modulate the shape of defensive peripersonal space.

The potential damage caused by an environmental threat increases with proximity to the body, so animals perform more effective and stronger defensive responses when threatening stimuli occur nearby the body, in a region termed the defensive peripersonal space (DPPS) [1,2]. We recently characterized the fine-grained geometry of the face's DPPS by recording the enhancement of the blink reflex elicited by electrical stimulation of the median nerve (hand-blink reflex, HBR), when the hand is closer to the face [3]. The resulting DPPS has the shape of a bubble, elongated asymmetrically along the rostro-caudal axis, extending further above eye-level [4]. We hypothesized that this vertical asymmetry is determined by gravitational cues: the probability that a threat will hit the body is higher when it comes from above. By systematically altering body posture, we show that the extent of DPPS asymmetry is defined in an earth-centred coordinate frame. This observation suggests the brain takes gravitational cues to automatically update threat value in an adaptive mechanism that accounts for the simple fact that objects fall down.