It wasn't me! Motor activation from irrelevant spatial information in the absence of a response

Embodied cognition postulates that perceptual and motor processes serve higher-order cognitive faculties like language. A major challenge for embodied cognition concerns the grounding of abstract concepts. Here we zoom in on abstract spatial concepts and ask the question to what extent the sensorimotor system is involved in processing these. Most of the empirical support in favor of an embodied perspective on (abstract) spatial information has derived from so-called compatibility effects in which a task-irrelevant feature either facilitates (for compatible trials) or hinders (in incompatible trials) responding to the task-relevant feature. This type of effect has been interpreted in terms of (task-irrelevant) feature-induced response activation. The problem with such approach is that incompatible features generate an array of task relevant and irrelevant activations [e.g., in primary motor cortex (M1)], and lateral hemispheric interactions render it difficult to assign credit to the task-irrelevant feature per se in driving these activations. Here, we aim to obtain a cleaner indication of response activation on the basis of abstract spatial information. We employed transcranial magnetic stimulation (TMS) to probe response activation of effectors in response to semantic, task-irrelevant stimuli (i.e., the words left and right) that did not require an overt response. Results revealed larger motor evoked potentials (MEPs) for the right (left) index finger when the word right (left) was presented. Our findings provide support for the grounding of abstract spatial concepts in the sensorimotor system

The neurocognitive underpinnings of the Simon effect: An integrative review of current research

Published online: 7 October 2020For as long as half a century the Simon task – in which participants respond to a nonspatial stimulus feature while ignoring its position – has represented a very popular tool to study a variety of cognitive functions, such as attention, cognitive control, and response preparation processes. In particular, the task generates two theoretically interesting effects: the Simon effect proper and the sequential modulations of this effect. In the present study, we review the main theoretical explanations of both kinds of effects and the available neuroscientific studies that investigated the neural underpinnings of the cognitive processes underlying the Simon effect proper and its sequential modulation using electroencephalogram (EEG) and event-related brain potentials (ERP), transcranial magnetic stimulation (TMS), and functional magnetic resonance imaging (fMRI). Then, we relate the neurophysiological findings to the main theoretical accounts and evaluate their validity and empirical plausibility, including general implications related to processing interference and cognitive control. Overall, neurophysiological research supports claims that stimulus location triggers the creation of a spatial code, which activates a spatially compatible response that, in incompatible conditions, interferes with the response based on the task instructions. Integration of stimulus-response features plays a major role in the occurrence of the Simon effect (which is manifested in the selection of the response) and its modulation by sequential congruency effects. Additional neural mechanisms are involved in supporting the correct and inhibiting the incorrect response.This research was supported by the Basque Government through the BERC 2018-2021 program and by the Spanish State Research Agency through BCBL Severo Ochoa excellence accreditation SEV-2015-0490 This study was also funded by Juan de la Cierva-Incorporación (Spanish government; JC) and European Commission (Marie Skłodowska-Curie actions 838536_BILINGUALPLAS; JC), by post-doctoral funding of the University of Bremen (DG; ZF 11/876/08), and by an ERC Advanced Grant (BH: ERC-2015-AdG-694722)

Temporal dynamics of target selection and distractor suppression mechanisms in the right Frontal Eye Field

The ability of the human brain to selectively attend to relevant information while ignoring irrelevant distraction is essential for the successful completion of everyday tasks. The present PhD project aimed to unravel the temporal dynamics of target selection and distractor suppression in the Frontal Eye Field (FEF), a key node in the dorsolateral attention network. Previous research (Lega et al., 2019) had assessed the contribution of both IPS and FEF to the deployment of visuo- spatial attention by means of 10 Hz TMS during a visual search task. The stimulation was delivered in a post-stimulus epoch from 100 to 300 ms, considered crucial for attentional computations in visual search. This study found that the TMS protocol improved distractor suppression mechanisms, reducing the cost engendered by salient but task-irrelevant distractors. To further clarify the temporal contribution of right FEF to distractor suppression, two experiments were carried out. Experiment 1 applied single-pulse TMS over right FEF at three different time points, 50, 200 or 350 ms after search array onset. Experiment 2 aimed to exert a stronger TMS effect over right FEF while maintaining a temporal-punctate approach. It applied trains of triple-pulse TMS at 20 Hz over right FEF in three different time windows: from -50 to 50 ms (T1), from 100 to 200 ms (T2) and from 250 to 350 ms (T3) after the search array onset. While Experiment 1 showed only a general, time-unspecific and quasi- significant effect of stimulation over response times, Experiment 2 revealed that stimulation at T2 (100-200 ms) was associated with an increase of the distractor cost, specifically for distractors located contralaterally to the stimulation site. These findings support the role of right FEF in suppressing distractions from salient but irrelevant stimuli and suggest that TMS may activate/inhibit the neural network that regulates and limits interference from such distractions. Further research is needed to precisely assess the physiological effects of different TMS protocols of the right FEF and its influence on attentional computation

Sensorimotor integration in dystonia: pathophysiology and possible non-invasive approaches to therapy

Dystonia is a condition characterized by excessive and sustained muscle contractions causing abnormal postures and involuntary movements. The pathophysiology of dystonia includes loss of inhibition and abnormal plasticity in the somatosensory and motor systems; however, their contribution to the phenomenology of dystonia is still uncertain, and the possibility to target these abnormalities in an attempt to devise new treatments has not been thoroughly explored. This thesis describes how abnormal inhibition and plasticity in the somatosensory system of dystonic patients can be manipulated to ameliorate motor symptoms by means of peripheral stimulation. First, we characterized electrophysiological and behavioural markers of inhibition in the primary somatosensory cortex in a group of patients with idiopathic cervical dystonia (CD). Outcome measures included a) somatosensory temporal discrimination threshold (STDT); b) paired-pulse somatosensory evoked potentials (PP-SEP) tested with interstimulus intervals (ISIs) of 5, 20 and 40 ms; c) spatial somatosensory inhibition ratio (SIR) by measuring SEP interaction between simultaneous stimulation of the digital nerves in thumb and index finger; d) high-frequency oscillations (HFO) extracted from SEP obtained with stimulation of digital nerves of the index finger. This first investigation demonstrated that increased STDT in dystonia is related to reduced activity of inhibitory circuits within the primary somatosensory cortex, as reflected by reduced PP-SEP inhibition at ISI of 5 ms and reduced area of the late part of the HFO (l-HFO). In a second set of experiments, we applied high frequency repetitive somatosensory stimulation (HF-RSS), a patterned electric stimulation applied to the skin through surface electrodes, to the index finger in a sample of healthy subjects, with the aim to manipulate excitability and inhibition of the primary somatosensory (S1) and motor (M1) cortices. The former was assessed by the same methods used before (STDT, PP-SEP, HFO), with the addition of two psychophysical tasks designed to assess tactile spatial discrimination (grating orientation and bumps tests). Assessment of physiology of M1 was performed by means of short intracortical inhibition (SICI) assessed with TMS; this was performed with multiple conditioning stimulus (CS) intensities (70%, 80%, 90% of the active motor threshold) and with a insterstimulus interval (ISI) between conditioning and test stimulus of 3 ms. It was found that HF-RSS increased inhibition in S1 tested by PP-SEP and HFO; these changes were correlated with improvement in STDT. HF-RSS also enhanced bumps detection, while there was no change in grating orientation test. Finally, there was an increase in SICI, suggesting widespread changes in cortical sensorimotor interactions. Overall, these findings demonstrated that HF-RSS is able to modify the effectiveness of inhibitory circuitry in S1 and M1. The results obtained so far led us to hypothesize that HF-RSS could restore inhibition in dystonic patients, similar to what observed in healthy subjects. To test this, we applied HF-RSS on the index finger in a sample of patients with CD, and tested its effects with some of the outcome measures used before (STDT, PP-SEP, HFO, SIR, SICI). Unexpectedly, the results were opposite to what was predicted. Patients with CD showed a consistent, paradoxical response: after HF-RSS, they had reduced suppression of PP-SEP, as well as decreased HFO area and SICI, and increased SIR. STDT deteriorated after the stimulation protocol, and correlated with reduced measures of inhibition within S1 (PP-SEP at 5 ms ISI, l-HFO area). It was hypothesized that patients with CD have abnormal homeostatic inhibitory plasticity within the sensorimotor cortex and that this is responsible for their abnormal response to HF-RSS. Interestingly, this alteration in plasticity seems to be specific to idiopathic dystonia: when the same protocol was applied to patients with dystonia caused by lesions in the basal ganglia, the response was similar to healthy controls. This result suggests that reduced somatosensory inhibition and abnormal cortical plasticity are not strictly required for the clinical expression of dystonia, and that the abnormalities reported in idiopathic dystonia are not necessarily linked to basal ganglia damage. We then directed our attention to another form of peripheral electrical stimulation, delivered at low frequency (LF-RSS). Previous literature demonstrated that this pattern of stimulation had effects opposite to HF-RSS on tactile performance in healthy subjects; therefore, given the previous findings of abnormal response to HF-RSS in CD, we hypothesized that an inverse response might occur in these patients following LF-RSS as well. Our hypothesis was confirmed by the observation that LF-RSS, applied to the fingers in patients with CD, induced an increase in inhibition in the primary somatosensory and motor cortices. This was reflected by an improvement of STDT and an increase in PP-SEP suppression, HFO area and SICI. With this in mind, in the final project of the thesis, we tested the effects of HF-RSS and LF-RSS applied directly over two affected muscles in different groups of patients with focal hand dystonia (FHD), in an attempt to modulate involuntary muscle activity and, consequently, to ameliorate motor symptoms. Whereas HF-RSS was delivered synchronously over the two muscles, LF-RSS was given either synchronously or asynchronously. Outcome measures included a) PP-SEP obtained by direct stimulation of affected muscles, with ISIs of 5 and 30 ms; b) quantification of electromyographic (EMG) activity from tested muscles; c) SICI recorded from the affected muscles, with CS intensities ranging from 50% to 100% RMT and with an ISI of 3 ms; d) evaluation of hand function, assessed by the box and blocks test (BBT) and the nine-hole peg test (NHPT); e) SIR by measuring SEP interaction between simultaneous stimulation of the two muscles receiving repetitive stimulation. We confirmed the paradoxical response of dystonic patients to HF-RSS, which was reflected in decreased PP-SEP suppression and SICI and increased SIR. Importantly, this was paralleled by an increase in involuntary EMG activity and worse scores at the BBT and NHPT. This results were opposite when LF-RSS was delivered, either in its synchronous or asynchronous version, the latter being slightly more effective. Thus, LF-RSS was able to increase PP-SEP suppression and SICI, decrease SIR and reduce involuntary EMG activity, with consequent improvement in performance in the BBT and NHPT. Overall, our data provide novel insight into the neural mechanisms underlying loss of inhibition and deranged somatosensory plasticity in idiopathic dystonia and bring preliminary evidence that peripheral electrical stimulation can be used as a treatment in idiopathic focal hand dystonia

We Three: My Brain, My Homunculus, and Me

An unconscious sense of the body in all higher mammals is located in somatosensory and motor cortices, colloquially referred to as the Homunculus (H). The time has arrived to consider how H might engage in the dimensions of selfhood that go beyond embodiment. Surely, the neural network modules that process various dimensions of selfhood must at least access and interact with the H or a stored memory of it. In this review, I suggest that our traditional understanding of H is much too simplistic. This review specifies a set of experimental approaches that should enlarge our understanding of the brain mechanisms of selfhood

The Motor System at the heart of Decision-Making and Action Execution

In this Thesis, I synthesize 10 years of work on the role of the motor system in sensorimotor decision-making. First, a large part of the work we initially performed questioned the functional role of the motor system in the integration of so-called decision variables such as the reward associated with different actions, the sensory evidence in favor of each action or the level of urgency in a given context. To this end, although the exact methodology may have varied, the approach exploited has been to study either the impact of a perturbation of the primary motor cortex (M1) on the integration of such decision variables in decision behavior, or the influence of these variables on changes in M1 activity during the decision. More recently (2020 - present), we have been investigating the neural origin of some of the changes in M1 activity observed during decision-making. To answer this question, a "perturbation-and-measurement" approach is exploited: the activity of a structure at a distance from M1 is perturbed, and the impact on the changes in M1 activity during decision-making is measured. The thesis ends up with a personal reflection on this paradigmatic evolution and discusses some key questions to be addressed in our field of research.Comment: This is an Habilitation Thesis, written in Frenc