A Cortical Mechanism Linking Saliency Detection and Motor Reactivity in Rhesus Monkeys.

Sudden and surprising sensory events trigger neural processes that swiftly adjust behavior. To study the phylogenesis and the mechanism of this phenomenon, we trained two male rhesus monkeys to keep a cursor inside a visual target by exerting force on an isometric joystick. We examined the effect of surprising auditory stimuli on exerted force, scalp electroencephalographic (EEG) activity, and local field potentials (LFPs) recorded from the dorsolateral prefrontal cortex. Auditory stimuli elicited (1) a biphasic modulation of isometric force, a transient decrease followed by a corrective tonic increase, and (2) EEG and LFP deflections dominated by two large negative-positive waves (N70 and P130). The EEG potential was symmetrical and maximal at the scalp vertex, highly reminiscent of the human "vertex potential." Electrocortical potentials and force were tightly coupled: the P130 amplitude predicted the magnitude of the corrective force increase, particularly in the LFPs recorded from deep rather than superficial cortical layers. These results disclose a phylogenetically preserved corticomotor mechanism supporting adaptive behavior in response to salient sensory events.Significance Statement Survival in the natural world depends on an animal's capacity to adapt ongoing behavior to abrupt unexpected events. To study the neural mechanisms underlying this capacity, we trained monkeys to apply constant force on a joystick while we recorded their brain activity from the scalp and the prefrontal cortex contralateral to the hand holding the joystick. Unexpected auditory stimuli elicited a biphasic force modulation: a transient reduction followed by a corrective adjustment. The same stimuli also elicited EEG and LFP responses, dominated by a biphasic wave that predicted the magnitude of the behavioral adjustment. These results disclose a phylogenetically preserved corticomotor mechanism supporting adaptive behavior in response to unexpected events.

The blink reflex and its modulation - Part 1: Physiological mechanisms.

The blink reflex (BR) is a protective eye-closure reflex mediated by brainstem circuits. The BR is usually evoked by electrical supraorbital nerve stimulation but can be elicited by a variety of sensory modalities. It has a long history in clinical neurophysiology practice. Less is known, however, about the many ways to modulate the BR. Various neurophysiological techniques can be applied to examine different aspects of afferent and efferent BR modulation. In this line, classical conditioning, prepulse and paired-pulse stimulation, and BR elicitation by self-stimulation may serve to investigate various aspects of brainstem connectivity. The BR may be used as a tool to quantify top-down modulation based on implicit assessment of the value of blinking in a given situation, e.g., depending on changes in stimulus location and probability of occurrence. Understanding the role of non-nociceptive and nociceptive fibers in eliciting a BR is important to get insight into the underlying neural circuitry. Finally, the use of BRs and other brainstem reflexes under general anesthesia may help to advance our knowledge of the brainstem in areas not amenable in awake intact humans. This review summarizes talks held by the Brainstem Special Interest Group of the International Federation of Clinical Neurophysiology at the International Congress of Clinical Neurophysiology 2022 in Geneva, Switzerland, and provides a state-of-the-art overview of the physiology of BR modulation. Understanding the principles of BR modulation is fundamental for a valid and thoughtful clinical application (reviewed in part 2) (Gunduz et al., submitted).

Revisiting a classical theory of sensory specificity: assessing consistency and stability of thermosensitive spots.

Thermal sensitivity is not uniform across the skin, and is particularly high in small (∼1 mm2) regions termed "thermosensitive spots." These spots are thought to reflect the anatomical location of specialized thermosensitive nerve endings from single primary afferents. Thermosensitive spots provide foundational support for "labeled line" or specificity theory of sensory perception, which states that different sensory qualities are transmitted by separate and specific neural pathways. This theory predicts a highly stable relation between repetitions of a thermal stimulus and the resulting sensory quality, yet these predictions have rarely been tested systematically. Here, we present the qualitative, spatial, and repeatability properties of 334 thermosensitive spots on the dorsal forearm sampled across four separate sessions. In line with previous literature, we found that spots associated with cold sensations (112 cold spots, 34%) were more frequent than spots associated with warm sensations (41 warm spots, 12%). Still more frequent (165 spots, 49%) were spots that elicited inconsistent sensations when repeatedly stimulated by the same temperature. Remarkably, only 13 spots (4%) conserved their position between sessions. Overall, we show unexpected inconsistency of both the perceptual responses elicited by spot stimulation and of spot locations across time. These observations suggest reappraisals of the traditional view that thermosensitive spots reflect the location of individual thermosensitive, unimodal primary afferents serving as specific labeled lines for corresponding sensory qualities.NEW & NOTEWORTHY Thermosensitive spots are clustered rather than randomly distributed and have the highest density near the wrist. Surprisingly, we found that thermosensitive spots elicit inconsistent sensory qualities and are unstable over time. Our results question the widely believed notion that thermosensitive spots reflect the location of individual thermoreceptive, unimodal primary afferents that serve as labelled lines for corresponding sensory qualities.

Dusk2Dawn: an EEGLAB plugin for automatic cleaning of whole-night sleep electroencephalogram using Artifact Subspace Reconstruction.

Whole-night sleep electroencephalogram (EEG) is plagued by several types of large-amplitude artifacts. Common approaches to remove them are fraught with issues: channel interpolation, rejection of noisy intervals, and independent component analysis are time-consuming, rely on subjective user decisions, and result in signal loss. Artifact Subspace Reconstruction (ASR) is an increasingly popular approach to rapidly and automatically clean wake EEG data. Indeed, ASR adaptively removes large-amplitude artifacts regardless of their scalp topography or consistency throughout the recording. This makes ASR, at least in theory, a highly-promising tool to clean whole-night EEG. However, ASR crucially relies on calibration against a subset of relatively clean "baseline" data. This is problematic when the baseline changes substantially over time, as in whole-night EEG data. Here we tackled this issue and, for the first time, validated ASR for cleaning sleep EEG. We demonstrate that ASR applied out-of-the-box, with the parameters recommended for wake EEG, results in the dramatic removal of slow waves. We also provide an appropriate procedure to use ASR for automatic and rapid cleaning of whole-night sleep EEG data or any long EEG recording. Our procedure is freely available in Dusk2Dawn, an open-source plugin for EEGLAB.

Spontaneous dyadic behavior predicts the emergence of interpersonal neural synchrony.

Synchronization of neural activity across brains - Interpersonal Neural Synchrony (INS) - is emerging as a powerful marker of social interaction that predicts success of multi-person coordination, communication, and cooperation. As the origins of INS are poorly understood, we tested whether and how INS might emerge from spontaneous dyadic behavior. We recorded neural activity (EEG) and human behavior (full-body kinematics, eye movements, and facial expressions) while dyads of participants were instructed to look at each other without speaking or making co-verbal gestures. We made four fundamental observations. First, despite the absence of a structured social task, INS emerged spontaneously only when participants were able to see each other. Second, we show that such spontaneous INS, comprising specific spectral and topographic profiles, did not merely reflect intra-personal modulations of neural activity, but it rather reflected real-time and dyad-specific coupling of neural activities. Third, using state-of-art video-image processing and deep learning, we extracted the temporal unfolding of three notable social behavioral cues - body movement, eye contact, and smiling - and demonstrated that these behaviors also spontaneously synchronized within dyads. Fourth, we probed the correlates of INS in such synchronized social behaviors. Using cross-correlation and Granger causality analyses, we show that synchronized social behaviors anticipate and in fact Granger cause INS. These results provide proof-of-concept evidence for studying interpersonal neural and behavioral synchrony under natural and unconstrained conditions. Most importantly, the results suggest that INS could be conceptualized as an emergent property of two coupled neural systems: an entrainment phenomenon, promoted by real-time dyadic behavior.

Interpersonal synchronization of spontaneously generated body movements.

Interpersonal movement synchrony (IMS) is central to social behavior in several species. In humans, IMS is typically studied using structured tasks requiring participants to produce specific body movements. Instead, spontaneously generated (i.e., not instructed) movements have received less attention. To test whether spontaneous movements synchronize interpersonally, we recorded full-body kinematics from dyads of participants who were only asked to sit face-to-face and to look at each other. We manipulated interpersonal (i) visual contact and (ii) spatial proximity. We found that spontaneous movements synchronized across participants only when they could see each other and regardless of interpersonal spatial proximity. This synchronization emerged very rapidly and did not selectively entail homologous body parts (as in mimicry); rather, the synchrony generalized to nearly all possible combinations of body parts. Hence, spontaneous behavior alone can lead to IMS. More generally, our results highlight that IMS can be studied under natural and unconstrained conditions.

Neural processes responsible for the translation of sustained nociceptive inputs into subjective pain experience.

Tracking and predicting the temporal structure of nociceptive inputs is crucial to promote survival, as proper and immediate reactions are necessary to avoid actual or potential bodily injury. Neural activities elicited by nociceptive stimuli with different temporal structures have been described, but the neural processes responsible for translating nociception into pain perception are not fully elucidated. To tap into this issue, we recorded electroencephalographic signals from 48 healthy participants receiving thermo-nociceptive stimuli with 3 different durations and 2 different intensities. We observed that pain perception and several brain responses are modulated by stimulus duration and intensity. Crucially, we identified 2 sustained brain responses that were related to the emergence of painful percepts: a low-frequency component (LFC, < 1 Hz) originated from the insula and anterior cingulate cortex, and an alpha-band event-related desynchronization (α-ERD, 8-13 Hz) generated from the sensorimotor cortex. These 2 sustained brain responses were highly coupled, with the α-oscillation amplitude that fluctuated with the LFC phase. Furthermore, the translation of stimulus duration into pain perception was serially mediated by α-ERD and LFC. The present study reveals how brain responses elicited by nociceptive stimulation reflect the complex processes occurring during the translation of nociceptive information into pain perception.

A novel method to selectively elicit cold sensations without touch.

BACKGROUND: Thermal and tactile stimuli are transduced by different receptor classes. However, mechano- and thermo-sensitive afferents interact at spinal and supraspinal levels. Yet, most studies on responses to cooling stimuli are confounded by mechanical contact, making these interactions difficult to isolate. Methods for precise control of non-mechanical thermal stimulations remain challenging, particularly in the cold range. NEW METHOD: We developed a non-tactile, focal, temperature-controlled, multi-purpose cooling stimulator. This method controls the exposure of a target skin region to a dry-ice source. Using a thermal camera to monitor skin temperature, and adjusting the source-skin distance accordingly, we could deliver non-tactile cooling stimuli with customisable profiles, for studying different aspects of cold sensation. RESULTS: To validate our method, we measured absolute and relative thresholds for cold sensation without mechanical contact in 13 human volunteer participants, using the method of limits. We found that the absolute cold detection threshold was 32.71 oC ± 0.88 oC. This corresponded to a threshold relative to each participant's baseline skin temperature of - 1.08 oC ± 0.37 oC. COMPARISONS WITH EXISTING METHOD: Our method allows cooling stimulation without the confound of mechanical contact, in a controllable and focal manner. CONCLUSIONS: We report a non-contact cooling stimulator and accompanying control system. We used this to measure cold thresholds in the absence of confounding touch. Our method enables more targeted studies of both cold sensory pathways, and of cold-touch interactions.

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.

Towards a unified neural mechanism for reactive adaptive behaviour.

Surviving in natural environments requires animals to sense sudden events and swiftly adapt behaviour accordingly. The study of such Reactive Adaptive Behaviour (RAB) has been central to a number of research streams, all orbiting around movement science but progressing in parallel, with little cross-field fertilization. We first provide a concise review of these research streams, independently describing four types of RAB: (1) cortico-muscular resonance, (2) stimulus locked response, (3) online motor correction and (4) action stopping. We then highlight remarkable similarities across these four RABs, suggesting that they might be subserved by the same neural mechanism, and propose directions for future research on this topic.

Feedforward and feedback pathways of nociceptive and tactile processing in human somatosensory system: A study of dynamic causal modeling of fMRI data.

Nociceptive and tactile information is processed in the somatosensory system via reciprocal (i.e., feedforward and feedback) projections between the thalamus, the primary (S1) and secondary (S2) somatosensory cortices. The exact hierarchy of nociceptive and tactile information processing within this 'thalamus-S1-S2' network and whether the processing hierarchy differs between the two somatosensory submodalities remains unclear. In particular, two questions related to the ascending and descending pathways have not been addressed. For the ascending pathways, whether tactile or nociceptive information is processed in parallel (i.e., 'thalamus-S1' and 'thalamus-S2') or in serial (i.e., 'thalamus-S1-S2') remains controversial. For the descending pathways, how corticothalamic feedback regulates nociceptive and tactile processing also remains elusive. Here, we aimed to investigate the hierarchical organization for the processing of nociceptive and tactile information in the 'thalamus-S1-S2' network using dynamic causal modeling (DCM) combined with high-temporal-resolution fMRI. We found that, for both nociceptive and tactile information processing, both S1 and S2 received inputs from thalamus, indicating a parallel structure of ascending pathways for nociceptive and tactile information processing. Furthermore, we observed distinct corticothalamic feedback regulations from S1 and S2, showing that S1 generally exerts inhibitory feedback regulation independent of external stimulation whereas S2 provides additional inhibition to the thalamic activity during nociceptive and tactile information processing in humans. These findings revealed that nociceptive and tactile information processing have similar hierarchical organization within the somatosensory system in the human brain.

Hyperscanning Alone Cannot Prove Causality. Multibrain Stimulation Can.

Brains that work together, couple together through interbrain synchrony. Does interbrain synchrony causally facilitate social interaction? This question cannot be answered by simply recording from multiple brains (hyperscanning). It instead requires causal protocols entailing their simultaneous stimulation (multibrain stimulation). We highlight promising findings and future horizons of this nascent field.

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.

Cognitive gadgets and cognitive priors.

Some of the foundations of Heyes' radical reasoning seem to be based on a fractional selection of available evidence. Using an ethological perspective, we argue against Heyes' rapid dismissal of innate cognitive instincts. Heyes' use of fMRI studies of literacy to claim that culture assembles pieces of mental technology seems an example of incorrect reverse inferences and overlap theories pervasive in cognitive neuroscience.

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.

No temporal contrast enhancement of simple decreases in noxious heat.

Offset analgesia (OA) studies have found that small decreases in the intensity of a tonic noxious heat stimulus yield a disproportionately large amount of pain relief. In the classic OA paradigm, the decrease in stimulus intensity is preceded by an increase of equal size from an initial noxious level. Although the majority of researchers believe this temporal sequence of two changes is important for eliciting OA, it has also been suggested that the temporal contrast mechanism underlying OA may enhance detection of simple, isolated decreases in noxious heat. To test whether decreases in noxious heat intensity, by themselves, are perceived better than increases of comparable sizes, we used an adaptive two-interval alternative forced choice task to find perceptual thresholds for increases and decreases in radiant and contact heat. Decreases in noxious heat were more difficult to perceive than increases of comparable sizes from the same initial temperature of 45°C. In contrast, decreases and increases were perceived equally well within a common range of noxious temperatures (i.e., when increases started from 45°C and decreases started from 47°C). In another task, participants rated the pain intensity of heat stimuli that randomly and unpredictably increased, decreased, or remained constant. Ratings of unpredictable stimulus decreases also showed no evidence of perceptual enhancement. Our results demonstrate that there is no temporal contrast enhancement of simple, isolated decreases in noxious heat intensity. Combined with previous OA findings, they suggest that long-lasting noxious stimuli that follow an increase-decrease pattern may be important for eliciting the OA effect. NEW & NOTEWORTHY Previous research suggested that a small decrease in noxious heat intensity feels surprisingly large because of sensory enhancement of noxious stimulus offsets (a simplified form of "offset analgesia"). Using a two-alternative forced choice task where participants detected simple increases or decreases in noxious heat, we showed that decreases in noxious heat, by themselves, are no better perceived than increases of comparable sizes. This suggests that a decrease alone is not sufficient to elicit offset analgesia.

The search for pain biomarkers in the human brain.

Non-invasive functional brain imaging is used more than ever to investigate pain in health and disease, with the prospect of finding new means to alleviate pain and improve patient wellbeing. The observation that several brain areas are activated by transient painful stimuli, and that the magnitude of this activity is often graded with pain intensity, has prompted researchers to extract features of brain activity that could serve as biomarkers to measure pain objectively. However, most of the brain responses observed when pain is present can also be observed when pain is absent. For example, similar brain responses can be elicited by salient but non-painful auditory, tactile and visual stimuli, and such responses can even be recorded in patients with congenital analgesia. Thus, as argued in this review, there is still disagreement on the degree to which current measures of brain activity exactly relate to pain. Furthermore, whether more recent analysis techniques can be used to identify distributed patterns of brain activity specific for pain can be only warranted using carefully designed control conditions. On a more general level, the clinical utility of current pain biomarkers derived from human functional neuroimaging appears to be overstated, and evidence for their efficacy in real-life clinical conditions is scarce. Rather than searching for biomarkers of pain perception, several researchers are developing biomarkers to achieve mechanism-based stratification of pain conditions, predict response to medication and offer personalized treatments. Initial results with promising clinical perspectives need to be further tested for replicability and generalizability.