Reflections on the past two decades of neuroscience.

The first issue of Nature Reviews Neuroscience was published 20 years ago, in 2000. To mark this anniversary, in this Viewpoint article we asked a selection of researchers from across the field who have authored pieces published in the journal in recent years for their thoughts on notable and interesting developments in neuroscience, and particularly in their areas of the field, over the past two decades. They also provide some thoughts on current lines of research and questions that excite them.

Aesthetic experience enhances first-person spatial representation.

Episodic autobiographical memories are characterized by a spatial context and an affective component. But how do affective and spatial aspects interact? Does affect modulate the way we encode the spatial context of events? We investigated how one element of affect, namely aesthetic liking, modulates memory for location, in three online experiments (n = 124, 79, and 80). Participants visited a professionally curated virtual art exhibition. They then relocated previously viewed artworks on the museum map and reported how much they liked them. Across all experiments, liking an artwork was associated with increased ability to recall the wall on which it was hung. The effect was not explained by viewing time and appeared to modulate recognition speed. The liking-wall memory effect remained when participants attended to abstractness, rather than liking, and when testing occurred 24 h after the museum visit. Liking also modulated memory for the room where a work of art was hung, but this effect primarily involved reduced room memory for disliked artworks. Further, the liking-wall memory effect remained after controlling for effects of room memory. Recalling the wall requires recalling one's facing direction, so our findings suggest that positive aesthetic experiences enhance first-person spatial representations. More generally, a first-person component of positive affect transfers to wider spatial representation and facilitates the encoding of locations in a subject-centered reference frame. Affect and spatial representations are therefore important, and linked, elements of sentience and subjectivity. Memories of aesthetic experiences are also spatial memories of how we encountered a work of art. This linkage may have implications for museum design.

Active self-touch restores bodily proprioceptive spatial awareness following disruption by 'rubber hand illusion'.

Bodily self-awareness relies on a constant integration of visual, tactile, proprioceptive, and motor signals. In the 'rubber hand illusion' (RHI), conflicting visuo-tactile stimuli lead to changes in self-awareness. It remains unclear whether other, somatic signals could compensate for the alterations in self-awareness caused by visual information about the body. Here, we used the RHI in combination with robot-mediated self-touch to systematically investigate the role of tactile, proprioceptive and motor signals in maintaining and restoring bodily self-awareness. Participants moved the handle of a leader robot with their right hand and simultaneously received corresponding tactile feedback on their left hand from a follower robot. This self-touch stimulation was performed either before or after the induction of a classical RHI. Across three experiments, active self-touch delivered after-but not before-the RHI, significantly reduced the proprioceptive drift caused by RHI, supporting a restorative role of active self-touch on bodily self-awareness. The effect was not present during involuntary self-touch. Unimodal control conditions confirmed that both tactile and motor components of self-touch were necessary to restore bodily self-awareness. We hypothesize that active self-touch transiently boosts the precision of proprioceptive representation of the touched body part, thus counteracting the visual capture effects that underlie the RHI.

Rapid Compensation for Noisy Voluntary Movements in Adults with Primary Tic Disorders.

BACKGROUND: It has been proposed that tics and premonitory urges in primary tic disorders (PTD), like Tourette syndrome, are a manifestation of sensorimotor noise. However, patients with tics show no obvious movement imprecision in everyday life. One reason could be that patients have strategies to compensate for noise that disrupts performance (ie, noise that is task-relevant). OBJECTIVES: Our goal was to unmask effects of elevated sensorimotor noise on the variability of voluntary movements in patients with PTD. METHODS: We tested 30 adult patients with PTD (23 male) and 30 matched controls in a reaching task designed to unmask latent noise. Subjects reached to targets whose shape allowed for variability either in movement direction or extent. This enabled us to decompose variability into task-relevant versus less task-relevant components, where the latter should be less affected by compensatory strategies than the former. In alternating blocks, the task-relevant target dimension switched, allowing us to explore the temporal dynamics with which participants adjusted movement variability to changes in task demands. RESULTS: Both groups accurately reached to targets, and adjusted movement precision based on target shape. However, when task-relevant dimensions of the target changed, patients initially produced movements that were more variable than controls, before regaining precision after several reaches. This effect persisted across repeated changes in the task-relevant dimension across the experiment, and therefore did not reflect an effect of novelty, or differences in learning. CONCLUSIONS: Our results suggest that patients with PTD generate noisier voluntary movements compared with controls, but rapidly compensate according to current task demands. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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.

Mistaking opposition for autonomy: psychophysical studies on detecting choice bias.

Do people know when they act freely and autonomously versus when their actions are influenced? While the human aspiration to freedom is widespread, little research has investigated how people perceive whether their choices are biased. Here, we explored how actions congruent or incongruent with suggestions are perceived as influenced or free. Across three experiments, participants saw directional stimuli cueing left or right manual responses. They were instructed to follow the cue's suggestion, oppose it or ignore it entirely to make a 'free' choice. We found that we could bias participants' 'free responses' towards adherence or opposition, by making one instruction more frequent than the other. Strikingly, participants consistently reported feeling less influenced by cues to which they responded incongruently, even when response habits effectively biased them towards such opposition behaviour. This effect was so compelling that cues that were frequently presented with the Oppose instruction became systematically judged as having less influence on behaviour, artificially increasing the sense of freedom of choice. Taken together, these findings demonstrate that acting contrarian distorts the perception of autonomy. Crucially, we demonstrate the existence of a novel illusion of freedom evoked by trained opposition. Our results have important implications for understanding mechanisms of persuasion.

Implicit signatures of voluntary action reduce with repeated motor practice.

The sense of controlling one's actions and their consequences is a critical aspect of successful motor activity. While motor performance typically improves with learning, it is unclear whether, how, and why higher order aspects of motor cognition are also affected. Here, we used an implicit measure of sense of agency-the 'intentional binding' effect-as participants learned to make a skilled action involving precise control of thumb adduction. These actions were predictably followed by a tone (the outcome). At pre-test, we showed the perceived time of the tone was shifted towards the thumb action, compared to a control condition in which tones occurred without actions. Next, a relevant training group learned to refine the direction of the thumb movement, while an irrelevant training group was trained on another movement. Manipulation checks demonstrated that, as expected, the relevant training group improved performance of the trained movement, while the irrelevant training group did not. Critically, while both groups still showed binding of the tone towards the thumb action at post-test, the relevant training group showed less binding than the irrelevant training group. Given the link between intentional binding and volitional control of action, we suggest our result demonstrates subjective agency over the outcome of a skilled action decreases as practice makes the skilled action more fluent. We suggest that this reduction in sense of agency over movement outcomes is consistent with the decreasing cognitive engagement, or automatization, that occurs during skill learning.

EEG Frequency Tagging Reveals the Integration of Form and Motion Cues into the Perception of Group Movement.

The human brain has dedicated mechanisms for processing other people's movements. Previous research has revealed how these mechanisms contribute to perceiving the movements of individuals but has left open how we perceive groups of people moving together. Across three experiments, we test whether movement perception depends on the spatiotemporal relationships among the movements of multiple agents. In Experiment 1, we combine EEG frequency tagging with apparent human motion and show that posture and movement perception can be dissociated at harmonically related frequencies of stimulus presentation. We then show that movement but not posture processing is enhanced when observing multiple agents move in synchrony. Movement processing was strongest for fluently moving synchronous groups (Experiment 2) and was perturbed by inversion (Experiment 3). Our findings suggest that processing group movement relies on binding body postures into movements and individual movements into groups. Enhanced perceptual processing of movement synchrony may form the basis for higher order social phenomena such as group alignment and its social consequences.

Multidigit tactile perception I: motion integration benefits for tactile trajectories presented bimanually.

Interactions with objects involve simultaneous contact with multiple, not necessarily adjacent, skin regions. Although advances have been made in understanding the capacity to selectively attend to a single tactile element among distracting stimulations, here, we examine how multiple stimulus elements are explicitly integrated into an overall tactile percept. Across four experiments, participants averaged the direction of two simultaneous tactile motion trajectories of varying discrepancy delivered to different fingerpads. Averaging performance differed between within- and between-hands conditions in terms of sensitivity and precision but was unaffected by somatotopic proximity between stimulated fingers. First, precision was greater in between-hand compared with within-hand conditions, demonstrating a bimanual perceptual advantage in multi-touch integration. Second, sensitivity to the average direction was influenced by the discrepancy between individual motion signals, but only for within-hand conditions. Overall, our experiments identify key factors that influence perception of simultaneous tactile events. In particular, we show that multi-touch integration is constrained by hand-specific rather than digit-specific mechanisms.NEW & NOTEWORTHY Object manipulation involves encoding spatially and temporally extended tactile signals, yet most studies emphasize minimal units of tactile perception (e.g., selectivity). Instead, we asked participants to average two tactile motion trajectories delivered simultaneously to two different fingerpads. Our results show strong integration between multiple tactile inputs, but subject to limitations for inputs delivered within a hand. As such, the present study establishes a paradigm for studying unified experience of touch despite distinct stimulus elements.

Evidence that endpoint feedback facilitates intermanual transfer of visuomotor force learning by a cognitive strategy.

Humans continuously adapt their movement to a novel environment by recalibrating their sensorimotor system. Recent evidence, however, shows that explicit planning to compensate for external changes, i.e., a cognitive strategy, can also aid performance. If such a strategy is planned in external space, it should improve performance in an effector-independent manner. We tested this hypothesis by examining whether promoting a cognitive strategy during a visual-force adaptation task performed in one hand can facilitate learning for the opposite hand. Participants rapidly adjusted the height of visual bar on screen to a target level by isometrically exerting force on a handle using their right hand. Visuomotor gain increased during the task and participants learned the increased gain. Visual feedback was continuously provided for one group, whereas for another group only the endpoint of the force trajectory was presented. The latter has been reported to promote cognitive strategy use. We found that endpoint feedback produced stronger intermanual transfer of learning and slower response times than continuous feedback. In a separate experiment, we found evidence that aftereffects are reduced when only endpoint feedback is provided, a finding that has been consistently observed when cognitive strategies are used. The results suggest that intermanual transfer can be facilitated by a cognitive strategy. This indicates that the behavioral observation of intermanual transfer can be achieved either by forming an effector-independent motor representation or by sharing an effector-independent cognitive strategy between the hands.NEW & NOTEWORTHY The causes and consequences of cognitive strategy use are poorly understood. We tested whether a visuomotor task learned in a manner that may promote cognitive strategy use causes greater generalization across effectors. Visual feedback was manipulated to promote cognitive strategy use. Learning consistent with cognitive strategy use for one hand transferred to the unlearned hand. Our result suggests that intermanual transfer can result from a common cognitive strategy used to control both hands.

Interhemispheric communication during haptic self-perception.

During the haptic exploration of a planar surface, slight resistances against the hand's movement are illusorily perceived as asperities (bumps) in the surface. If the surface being touched is one's own skin, an actual bump would also produce increased tactile pressure from the moving finger onto the skin. We investigated how kinaesthetic and tactile signals combine to produce haptic perceptions during self-touch. Participants performed two successive movements with the right hand. A haptic force-control robot applied resistances to both movements, and participants judged which movement was felt to contain the larger bump. An additional robot delivered simultaneous but task-irrelevant tactile stroking to the left forearm. These strokes contained either increased or decreased tactile pressure synchronized with the resistance-induced illusory bump encountered by the right hand. We found that the size of bumps perceived by the right hand was enhanced by an increase in left tactile pressure, but also by a decrease. Tactile event detection was thus transferred interhemispherically, but the sign of the tactile information was not respected. Randomizing (rather than blocking) the presentation order of left tactile stimuli abolished these interhemispheric enhancement effects. Thus, interhemispheric transfer during bimanual self-touch requires a stable model of temporally synchronized events, but does not require geometric consistency between hemispheric information, nor between tactile and kinaesthetic representations of a single common object.

Sense of agency in the human brain.

In adult life, people normally know what they are doing. This experience of controlling one's own actions and, through them, the course of events in the outside world is called 'sense of agency'. It forms a central feature of human experience; however, the brain mechanisms that produce the sense of agency have only recently begun to be investigated systematically. This recent progress has been driven by the development of better measures of the experience of agency, improved design of cognitive and behavioural experiments, and a growing understanding of the brain circuits that generate this distinctive but elusive experience. The sense of agency is a mental and neural state of cardinal importance in human civilization, because it is frequently altered in psychopathology and because it underpins the concept of responsibility in human societies.

Misdirected attentional focus in functional tremor.

A characteristic and intriguing feature of functional neurological disorder is that symptoms typically manifest with attention and improve or disappear with distraction. Attentional phenomena are therefore likely to be important in functional neurological disorder, but exactly how this manifests is unknown. The aim of the study was to establish whether in functional tremor the attentional focus is misdirected, and whether this misdirection is detrimental to the movement, or rather reflects a beneficial compensatory strategy. Patients with a functional action tremor, between the ages of 21-75, were compared to two age and gender matched control groups: healthy control participants and patients with an organic action tremor. The groups included between 17 and 28 participants. First, we compared the natural attentional focus on different aspects of a reaching movement (target, ongoing visual feedback, proprioceptive-motor aspect). This revealed that the attentional focus in the functional tremor group, in contrast to both control groups, was directed to ongoing visual feedback from the movement. Next, we established that all groups were able to shift their attentional focus to different aspects of the reaching movement when instructed. Subsequently, the impact of attentional focus on the ongoing visual feedback on movement performance was evaluated under several conditions: the reaching movement was performed with direct, or indirect visual feedback, without any visual feedback, under three different instruction conditions (as accurately as possible/very slowly/very quickly) and finally as a preparatory movement that was supposedly of no importance. Low trajectory length and low movement duration were taken as measures of good motor performance. For all three groups, motor performance deteriorated with attention to indirect visual feedback, to accuracy and when instructed to move slowly. It improved without visual feedback and when instructed to move fast. Motor performance improved, in participants with functional tremor only, when the movement was performed as a preparatory movement without any apparent importance. In addition to providing experimental evidence for improvement with distraction, we found that the normal allocation of attention during aimed movement is altered in functional tremor. Attention is disproportionately directed towards the ongoing visual feedback from the moving hand. This altered attentional focus may be partly responsible for the tremor, since it also worsens motor performance in healthy control participants and patients with an organic action tremor. It may have its detrimental impact through interference with automatic movement processes, due to a maladaptive shift from lower- to higher-level motor control circuitry.

Evidence accumulation under uncertainty - a neural marker of emerging choice and urgency.

To interact meaningfully with its environment, an agent must integrate external information with its own internal states. However, information about the environment is often noisy. In this study, we identify a neural correlate that tracks how asymmetries between competing alternatives evolve over the course of a decision. In our task participants had to monitor a stream of discrete visual stimuli over time and decide whether or not to act, on the basis of either strong or ambiguous evidence. We found that the classic P3 event-related potential evoked by sequential evidence items tracked decision-making processes and predicted participants' categorical choices on a single trial level, both when evidence was strong and when it was ambiguous. The P3 amplitudes in response to evidence supporting the eventually selected option increased over trial time as decisions evolved, being maximally different from the P3 amplitudes evoked by competing evidence at the time of decision. Computational modelling showed that both the neural dynamics and behavioural primacy and recency effects can be explained by a combination of (a) competition between mutually inhibiting accumulators for the two categorical choice outcomes, and (b) a context-dependant urgency signal. In conditions where evidence was presented at a low rate, urgency increased faster than in conditions when evidence was very frequent. We also found that the readiness potential, a classic marker of endogenously initiated actions, was observed preceding movements in all conditions - even when those were strongly driven by external evidence.

The Readiness Potential reflects the internal source of action, rather than decision uncertainty.

Voluntary actions are preceded by a Readiness Potential (RP), a slow EEG (electroencephalogram) component generated in medial frontal cortical areas. The RP is classically thought to be specific to internally-driven decisions to act, and to reflect post-decision motor preparation. Recent work suggests instead that it may reflect noise or conflict during the decision itself, with internally driven decisions tending to be more random, more conflicted and thus more uncertain than externally driven actions. To contrast accounts based on endogenicity with accounts based on uncertainty, we recorded EEG in a task where participants decided to act or withhold action to accept or reject visually presented gambles, and used multivariate methods to extract an RP-like component. We found no difference in amplitude of this component between actions driven by strong versus weak evidence, suggesting that the RP may not reflect uncertainty. In contrast, the same RP-like component showed higher amplitudes prior to actions performed without any external evidence (guesses) than for actions performed in response to equivocal, conflicting evidence. This supports the view that the RP reflects the internal source of action, rather than decision uncertainty.

Touch inhibits touch: sanshool-induced paradoxical tingling reveals perceptual interaction between somatosensory submodalities.

Human perception of touch is mediated by inputs from multiple channels. Classical theories postulate independent contributions of each channel to each tactile feature, with little or no interaction between channels. In contrast to this view, we show that inputs from two sub-modalities of mechanical input channels interact to determine tactile perception. The flutter-range vibration channel was activated anomalously using hydroxy-α-sanshool, a bioactive compound of Szechuan pepper, which chemically induces vibration-like tingling sensations. We tested whether this tingling sensation on the lips was modulated by sustained mechanical pressure. Across four experiments, we show that sustained touch inhibits sanshool tingling sensations in a location-specific, pressure-level and time-dependent manner. Additional experiments ruled out the mediation of this interaction by nociceptive or affective (C-tactile) channels. These results reveal novel inhibitory influence from steady pressure onto flutter-range tactile perceptual channels, consistent with early-stage interactions between mechanoreceptor inputs within the somatosensory pathway.

The Phenomenon of Exquisite Motor Control in Tic Disorders and its Pathophysiological Implications.

The unifying characteristic of movement disorders is the phenotypic presentation of abnormal motor outputs, either as isolated phenomena or in association with further clinical, often neuropsychiatric, features. However, the possibility of a movement disorder also characterized by supranormal or enhanced volitional motor control has not received attention. Based on clinical observations and cases collected over a number of years, we here describe the intriguing clinical phenomenon that people with tic disorders are often able to control specific muscle contractions as part of their tic behaviors to a degree that most humans typically cannot. Examples are given in accompanying video documentation. We explore medical literature on this topic and draw analogies with early research of fine motor control physiology in healthy humans. By systematically analyzing the probable sources of this unusual capacity, and focusing on neuroscientific accounts of voluntary motor control, sensory feedback, and the role of motor learning in tic disorders, we provide a novel pathophysiological account explaining both the presence of exquisite control over motor output and that of overall tic behaviors. We finally comment on key questions for future research on the topic and provide concluding remarks on the complex movement disorder of tic behaviors. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

No increased suggestibility to placebo in functional neurological disorder.

BACKGROUND AND PURPOSE: On the basis of occasional strong placebo responses, increased susceptibility to placebo has been proposed as a characteristic of functional neurological disorder (FND). The aim of this study was to clarify whether people with FND have a stronger placebo analgesic response than healthy controls. METHODS: A study using a classic placebo paradigm, with additional conditioning and open-label components, was performed in 30 patients with FND, and in 30 healthy controls. Ratings of mildly to moderately painful electrotactile stimuli were compared before and after the application of a placebo "anaesthetic" cream versus a control cream, after an additional conditioning exposure, and after full disclosure (open-label component). RESULTS: Pain intensity ratings at the placebo compared to the control site were similarly reduced in both groups. The conditioning exposure had no additional effect. After placebo disclosure a residual analgesic effect remained. CONCLUSION: Patients with FND did not have stronger placebo responses than healthy controls. The notion of generally increased suggestibility or increased suggestibility to placebo in FND seems mistaken. Instead, occasional dramatic placebo responses may occur because functional symptoms are inherently more changeable than those due to organic disease.

The vestibular system modulates the contributions of head and torso to egocentric spatial judgements.

Egocentric representations allow us to describe the external world as experienced from an individual's bodily location. We recently developed a novel method of quantifying the weight given to different body parts in egocentric judgments (the Misalignment Paradigm). We found that both head and torso contribute to simple alter-egocentric spatial judgments. We hypothesised that artificial stimulation of the vestibular system would provide a head-related signal, which might affect the weighting given to the head in egocentric spatial judgments. Bipolar Galvanic Vestibular Stimulation (GVS) was applied during the Misalignment Paradigm. A Sham stimulation condition was also included to control for non-specific effects. Our data show that the weight given to the head was increased during left anodal and right cathodal GVS, compared to the opposite GVS polarity (right anodal and left cathodal GVS) and Sham stimulation. That is, the polarity of GVS, which preferentially activates vestibular areas in the right cerebral hemisphere, influenced the relative weightings of head and torso in egocentric spatial judgments.

Decoding Changes of Mind in Voluntary Action-Dynamics of Intentional Choice Representations.

Voluntary actions rely on appropriate flexibility of intentions. Usually, we should pursue our goals, but sometimes we should change goals if they become too costly to achieve. Using functional magnetic resonance imaging, we investigated the neural dynamics underlying the capacity to change one's mind based on new information after action onset. Multivariate pattern analyses revealed that in visual areas, neural representations of intentional choice between 2 visual stimuli were unchanged by additional decision-relevant information. However, in fronto-parietal cortex, representations changed dynamically as decisions evolved. Precuneus, angular gyrus, and dorsolateral prefrontal cortex encoded new externally cued rewards/costs that guided subsequent changes of mind. Activity in medial frontal cortex predicted changes of mind when participants detached from externally cued evidence, suggesting a role in endogenous decision updates. Finally, trials with changes of mind were associated with an increase in functional connectivity between fronto-parietal areas, allowing for integration of various endogenous and exogenous decision components to generate a distributed consensus about whether to pursue or abandon an initial intention. In conclusion, local and global dynamics of choice representations in fronto-parietal cortex allow agents to maintain the balance between adapting to changing environments versus pursuing internal goals.