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When participants listen to a rhythm produced by a human performer, they are able to “follow” the rhythm even though it can contain relatively large fluctuations in periodicity. This is due to the fact that autocorrelated temporal fluctuations contain relevant information for beat expectation: the occurrence of the upcoming beat is predicted by the occurrences of the preceding beats1. The Dynamic Attending Theory2 proposes that the entrainment to nearly-periodic rhythms emerges from the dynamics of interaction between neural systems acting as “internal oscillators”. The internal oscillators are coupled by their anatomical connexions and, therefore, are able to mutually adjust their synchronization, even after the perturbation of one of the oscillators. Importantly, the internal oscillators generate a repetitive time window within which the system is expecting to receive a stimulation. The auditory events of an autocorrelated rhythm match those expectational windows better than those on an non-correlated, random, rhythm. Therefore, the autocorrelated rhythm would reinforce the neural oscillations, yielding a better neural entrainment than a randomly fluctuating rhythm. In this study, we recorded the EEG activity elicited by auditory beats with autocorrelated fluctuations versus non-correlated fluctuations, in order to provide a direct electrophysiological measure of dynamic attending in healthy human participants.

To understand the brain mechanisms underlying language phenomena, and sentence construction in particular, a number of approaches have been followed that are based on artificial neural networks, where words are encoded as distributed patterns of activity. Still, issues like the distinct encoding of semantic vs syntactic features, word binding, and the learning processes through which words come to be encoded that way, have remained tough challenges. We explore a novel approach to address these challenges, which focuses first on encoding words of an artificial language of intermediate complexity (BLISS) into a Potts attractor net. Such a network has the capability to spontaneously latch between attractor states, offering a simplified cortical model of sentence production. The network stores the BLISS vocabulary, and hopefully its grammar, in its semantic and syntactic subnetworks. Function and content words are encoded differently on the two subnetworks, as suggested by neuropsychological findings. We propose that a next step might describe the self-organization of a comparable representation of words through a model of a learning process.

Gaze following and the ability to understand that another individual sees something different from oneself are considered important components of human and animal social cognition. In animals, gaze following has been documented in various species, however, the underlying cognitive mechanisms and the evolution of this skill remain to be investigated. Therefore, in this thesis I addressed the cognitive mechanisms in a non-human primate and moreover I extended the range of investigated species to one that is phylogenetically more remote from humans, namely fish, in order to study the evolutionary history of this capacity. First, I demonstrated that long-tailed macaques follow the looking direction of a human experimenter. Subjects also ‘check-looked’, i.e. looked back and forth between the experimenter’s face and their gaze direction, which has been proposed to indicate that a subject understands that another individual is looking at a specific stimulus. Moreover, I found that gaze-shifts accompanied by a socially meaningful facial expression (mimicking a social event) elicited stronger gaze-following responses than neutral gaze-shifts. This modulation of gaze following may be due to a specific arousal- or attention-based mechanism or may be based on the subject understanding that the demonstrator is attending to something the subject cannot see. To further address these possibilities I investigated whether monkeys follow a conspecific’s gaze to a hidden location which would indicate a capacity to extrapolate the other’s line of sight to locations outside the field of vision. When a conspecific demonstrator gazed at a mirror hidden behind a barrier, subjects relocated to a position where they could see the mirror location and directed significantly more focussed looks behind the barrier than in a situation where there was no conspicuous gaze cue by the demonstrator. Taken together, these studies suggest that monkeys’ gaze following behaviour is a more flexible and accurate ability than has previously been shown. This capacity may thus be based on an appreciation of the fact that another’s gaze and attention can be directed at something specific. These results resemble findings in chimpanzees that have been associated with the ability to attribute perceptual states to others, which may be generically labelled ‘Theory of Mind’. Addressing the evolution of this ability, I extended the study of gaze following and a related capacity, visual perspective taking, to guppy fish. Research on social cognition has tended to focus on a restricted range of species, principally primates and, more recently, birds and some domesticated animals. However, remarkable similarities on a behavioural level have been documented for non-human primates and fish, behaviours that in primates have been used to assess advanced cognitive capacities. I found some evidence that guppies responded to the body orientation of others (potentially equivalent to gaze direction), but guppies failed to pass a visual perspective taking task. Further studies are required to confirm the present results and to address potential underlying mechanisms in this species. Altogether, this thesis is an example how evolutionary and mechanistic approaches to behaviour can be integrated and can shed new light on non-human animals’ cognitive capacities.

European neuropsychopharmacology : ENP 64, 63-71 (2022). doi:10.1016/j.euroneuro.2022.09.001, Published by Elsevier, Amsterdam

Background Cognitive stimulation therapy appears to show promising results in the rehabilitation of impaired cognitive processes in attention deficit hyperactivity disorder. Objective Encouraged by this evidence and the ever-increasing use of technology and artificial intelligence for therapeutic purposes, we examined whether cognitive stimulation therapy implemented on a mobile device and controlled by an artificial intelligence engine can be effective in the neurocognitive rehabilitation of these patients. Methods In this randomized study, 29 child participants (25 males) underwent training with a smart, digital, cognitive stimulation program (KAD_SCL_01) or with 3 commercial video games for 12 weeks, 3 days a week, 15 minutes a day. Participants completed a neuropsychological assessment and a preintervention and postintervention magnetoencephalography study in a resting state with their eyes closed. In addition, information on clinical symptoms was collected from the child´s legal guardians. Results In line with our main hypothesis, we found evidence that smart, digital, cognitive treatment results in improvements in inhibitory control performance. Improvements were also found in visuospatial working memory performance and in the cognitive flexibility, working memory, and behavior and general executive functioning behavioral clinical indexes in this group of participants. Finally, the improvements found in inhibitory control were related to increases in alpha-band power in all participants in the posterior regions, including 2 default mode network regions of the interest: the bilateral precuneus and the bilateral posterior cingulate cortex. However, only the participants who underwent cognitive stimulation intervention (KAD_SCL_01) showed a significant increase in this relationship. Conclusions The results seem to indicate that smart, digital treatment can be effective in the inhibitory control and visuospatial working memory rehabilitation in patients with attention deficit hyperactivity disorder. Furthermore, the relation of the inhibitory control with alpha-band power changes could mean that these changes are a product of plasticity mechanisms or changes in the neuromodulatory dynamics. Trial Registration ISRCTN Registry ISRCTN71041318; https://www.isrctn.com/ISRCTN71041318

Personal recovery transcends illness and is a unifying human experience. Core elements in personal recovery are hope, meaning, and rebuilding oneself. Here we aim to investigate whether factors associated with personal recovery in patients with non-affective psychosis, unaffected siblings and healthy controls are similar. We investigated the association between personal recovery and resilience, social support, socio-demographic and illness-related variables in 580 patients, 630 siblings, and 351 healthy controls who participated in the Genetic Risk and Outcome of Psychosis (GROUP) study. Bi-variate associations between personal recovery and individual variables were assessed and multiple linear regression analyses were performed to estimate the proportion of variance in personal recovery that could be accounted for by the predictors and to investigate which predictors independently added to the model. Positive self was significantly and independently associated with personal recovery in all three groups. Pro-active action taking also seems to be important. Social functioning significantly contributed to explained variance in patients and siblings. Regarding illness-related factors, depressive symptoms had impact on personal recovery in both patients and siblings, whereas positive symptoms only did in siblings. The findings imply that not only personal recovery itself, but also some associated factors are universally human and suit us all. This means that patients and non-patients share supportive factors of personal recovery which may help to reach mutual understanding. Recovery-oriented practices and mental health services might be more effective when focusing also on improving self-image, functional coping styles and generating social interaction, next to the reduction of affective symptoms.

The perceived temporal order of actions and changes in the environment is crucial for our inferences of causality. Sensory events presented shortly after an action are more likely considered as self-generated compared to the same events occurring before action execution. However, the estimation of when an action or a sensory change occurred is a challenge for the human brain. This estimation is formed from available sensory information combined with internal representations. Researchers suggested that internal signals associated with action preparation drive our awareness of initiating an action. This study aimed to directly investigate this hypothesis. Participants performed a speeded action (left or right key-press) in response to a go-signal (left or right arrow). A flash was presented at different time points around the time of the action, and participants judged whether it was simultaneous with the action or not. To investigate the role of action preparation in time perception, we compared trials where a cue indicated which action to perform in response to a later go signal presentation, and trials with a neutral cue where participants did not know until the time of the go signal which action to perform. We observed that a flash presented before the action was reported as simultaneous with the action more frequently when actions were cued than when they were uncued. This difference was not observed when the action was replaced by a tactile stimulation. These results indicate that precued actions are experienced earlier in time compared to unprepared actions. Further, this difference is not due to mere non-motor expectation of an event. The experience of initiating an action is driven by action preparation process: when we know what to do, actions are perceived ahead of time. Electronic supplementary material The online version of this article (10.1007/s00221-018-5292-5) contains supplementary material, which is available to authorized users.

International audience; Interoceptive signals, such as the heartbeat, are processed in a network of brain regions including the insular cortex. Recent studies have shown that such signals modulate perceptual and cognitive processing, and that they impact visual awareness. For example, visual stimuli presented synchronously to the heartbeat take longer to enter visual awareness than the same stimuli presented asynchronously to the heartbeat, and this is reflected in anterior insular activation. This finding demonstrated a link between the processing of interoceptive and exteroceptive signals as well as visual awareness in the insular cortex. The advantage for visual stimuli which are asynchronous to the heartbeat to enter visual consciousness may indicate a role for the anterior insula in the suppression of the sensory consequences of cardiac signals. Here, we present data from the detailed investigation of two patients with insular lesions (as well as four patients with non-insular lesions and healthy age matched controls) indicating that a lesion of the anterior insular cortex, but not of other regions, abolished this cardio-visual suppression effect. The present data provide causal evidence for the role of the anterior insula in the integration of internal interoceptive and external sensory signals for visual awareness.

International audience; In physics “entrainment” refers to the synchronization of two coupled oscillators with similar fundamental frequencies. In behavioral science, entrainment refers to the tendency of humans to synchronize their movements with rhythmic stimuli. Here, we asked whether human subjects performing a tapping task would entrain their tapping to an undetected auditory rhythm surreptitiously introduced in the guise of ambient background noise in the room. Subjects performed two different tasks, one in which they tapped their finger at a steady rate of their own choosing and one in which they performed a single abrupt finger tap on each trial after a delay of their own choosing. In both cases we found that subjects tended to tap in phase with the inducing modulation, with some variability in the preferred phase across subjects, consistent with prior research. In the repetitive tapping task, if the frequency of the inducing stimulus was far from the subject’s own self-paced frequency, then entrainment was abolished, consistent with the properties of entrainment in physics. Thus, undetected ambient noise can influence self-generated movements. This suggests that uncued decisions to act are never completely endogenous, but are subject to subtle unnoticed influences from the sensory environment.

Background and Hypothesis Approximately one-third of patients with a psychotic disorder experience visual hallucinations (VH). While new, more targeted treatment options are warranted, the pathophysiology of VH remains largely unknown. Previous studies hypothesized that VH result from impaired functioning of the vision-related networks and impaired interaction between those networks, including a possible functional disconnection between the primary visual cortex (V1) and higher-order visual processing regions. Testing these hypotheses requires sufficient data on brain activation during actual VH, but such data are extremely scarce. Study Design We therefore recruited seven participants with a psychotic disorder who were scanned in a 3 T fMRI scanner while indicating the occurrence of VH by pressing a button. Following the scan session, we interviewed participants about the VH experienced during scanning. We then used the fMRI scans to identify regions with increased or decreased activity during VH periods versus baseline (no VH). Study Results In six participants, V1 was not activated during VH, and in one participant V1 showed decreased activation. All participants reported complex VH such as human-like beings, objects and/or animals, during which higher-order visual areas and regions belonging to the vision-related networks on attention and memory were activated. Discussion These results indicate that VH are associated with diffuse involvement of the vision-related networks, with the exception of V1. We therefore propose a model for the pathophysiology of psychotic VH in which a dissociation of higher-order visual processing areas from V1 biases conscious perception away from reality and towards internally generated percepts.

Background and Hypothesis Patients with hearing impairment (HI) may experience hearing sounds without external sources, ranging from random meaningless noises (tinnitus) to music and other auditory hallucinations (AHs) with meaningful qualities. To ensure appropriate assessment and management, clinicians need to be aware of these phenomena. However, sensory impairment studies have shown that such clinical awareness is low. Study Design An online survey was conducted investigating awareness of AHs among clinicians and their opinions about these hallucinations. Study Results In total, 125 clinicians (68.8% audiologists; 18.4% Ear-Nose-Throat [ENT] specialists) across 10 countries participated in the survey. The majority (96.8%) was at least slightly aware of AHs in HI. About 69.6% of participants reported encountering patients with AHs less than once every 6 months in their clinic. Awareness was significantly associated with clinicians’ belief that patients feel anxious about their hallucinations (β = .018, t(118) = 2.47, P < .01), their belief that clinicians should be more aware of these hallucinations (β =.018, t(118) = 2.60, P < .01), and with confidence of clinicians in their skills to assess them (β = .017, t(118) = 2.63, P < .01). Clinicians felt underequipped to treat AHs (Median = 31; U = 1838; PFDRadj < .01). Conclusions Awareness of AHs among the surveyed clinicians was high. Yet, the low frequency of encounters with hallucinating patients and their belief in music as the most commonly perceived sound suggest unreported cases. Clinicians in this study expressed a lack of confidence regarding the assessment and treatment of AHs and welcome more information.

PURPOSE: The aim of this study was to determine the association between caffeine intake and dry eye disease (DED) in the large, population-based LifeLines cohort in the Netherlands. METHODS: DED was cross-sectionally assessed in 85,302 participants (59% female participants) using the Women's Health Study dry eye questionnaire. Dietary caffeine was calculated from the intake of coffee, tea, cola, and energy drinks. Logistic regression was used to investigate the relationship between DED and caffeine, correcting for demographic variables, smoking status, alcohol intake, and 48 comorbidities of DED. RESULTS: The mean (SD; range) age of participants was 50.7 years (12.4; 18-96), and 50,339 (59%) were female. The mean (SD) caffeine intake was 285 (182) mg/d. After correcting for demographics, body mass index, smoking status, and alcohol intake, higher caffeine intake was associated with a decreased risk of Women's Health Study-defined DED [odds ratio (OR) 0.971 per 100 mg/d, 95% CI, 0.956-0.986, P < 0.0005]. When additionally adjusting for medical comorbidities, no significant effect was observed (OR 0.985, 95% CI, 0.969-1.001, P = 0.06). Caffeine's effect on DED was similar in male and female participants and independent of sleep quality and stress at work. Decaffeinated coffee intake was significantly associated with an increased risk of DED, when adjusted for caffeinated coffee, demographics, alcohol intake, smoking status, and comorbidities (OR 1.046 per cup/d, 95% CI, 1.010-1.084, P = 0.01). None of the beverages were significantly associated with the risk of DED, when correcting for intake of the other caffeinated beverages, demographics, smoking status, alcohol intake, and all comorbidities. CONCLUSIONS: Dietary caffeine intake does not seem to be a risk factor for DED in the general population.

Objective: Standard nerve excitability testing (NET) predominantly assesses Aα- and Aβ-fiber function, but a method examining small afferents would be of great interest in pain studies. Here, we examined the properties of a novel perception threshold tracking (PTT) method that preferentially activates Aδ-fibers using weak currents delivered by a novel multipin electrode and compared its reliability with NET. Methods: Eighteen healthy subjects (mean age:34.06 ± 2.0) were examined three times with motor and sensory NET and PTT in morning and afternoon sessions on the same day (intra-day reliability) and after a week (inter-day reliability). NET was performed on the median nerve, while PTT stimuli were delivered through a multipin electrode located on the forearm. During PTT, subjects indicated stimulus perception via a button press and the intensity of the current was automatically increased or decreased accordingly by Qtrac software. This allowed changes in the perception threshold to be tracked during strength-duration time constant (SDTC) and threshold electrotonus protocols. Results: The coefficient of variation (CoV) and interclass coefficient of variation (ICC) showed good–excellent reliability for most NET parameters. PTT showed poor reliability for both SDTC and threshold electrotonus parameters. There was a significant correlation between large (sensory NET) and small (PTT) fiber SDTC when all sessions were pooled (r = 0.29, p = 0.03). Conclusions: Threshold tracking technique can be applied directly to small fibers via a psychophysical readout, but with the current technique, the reliability is poor. Significance: Further studies are needed to examine whether Aβ-fiber SDTC may be a surrogate biomarker for peripheral nociceptive signalling.

Adequately learning to read and write is indispensable in our technological societies; however, it is an effortful process that requires years of formal education. In transparent alphabetic orthographies, such as Dutch, the crucial building blocks for literacy skills are the correspondences between letters and speech sounds (LS pairs). Previously, we demonstrated that LS pairs reliably produce a congruency-sensitive fMRI response in the superior temporal cortex (STC) of Dutch fluent readers, but not in dyslexic readers. Here, we used fMRI to investigate whether a similar congruency-sensitivity exists in STC of readers of opaque orthographies, such as English, where the relation between letters and speech sounds is unreliable, and may therefore not provide a similarly important basis for literacy. Eighteen subjects passively perceived congruent and incongruent audiovisual pairs that have different transparencies in English: letters/speech sounds (LS; irregular), letters/letter names (LN; fairly transparent) and numerals/number names (NN; transparent). We detected a congruency by pair-type interaction in STC bilaterally, that was produced by a strong congruency effect for NN, a weaker one for LN, and an incongruency effect for LS. No congruency effects for LS pairs were found in the predicted direction (congruent > incongruent), in contrast to the previous results in Dutch readers. These results indicate that through education, the STC becomes tuned to the congruency of transparent audiovisual pairs, but suggest different neural processing of irregular pairs. This orthographic dependency of LS integration has important implications for remediation strategies for dyslexia in different languages.

Multimodal neuroimaging has become a mainstay of basic and cognitive neuroscience in humans and animals, despite challenges to consider when acquiring and combining non-redundant imaging data. Multimodal data integration can yield important insights into brain processes and structures in addition to spatiotemporal resolution complementarity, including: a comprehensive physiological view on brain processes and structures, quantification, generalization and normalization, and availability of biomarkers. In this review, we discuss data acquisition and fusion in multimodal neuroimaging in the context of each of these potential merits. However, limitations – due to differences in the neuronal and structural underpinnings of each method – have to be taken into account when modeling and interpreting multimodal data using generative models. We conclude that when these challenges are adequately met, multimodal data fusion can create substantial added value for neuroscience applications making it an indispensable approach for studying the brain.

International audience; Recent studies have highlighted the role of multisensory integration as a key mechanism of self-consciousness. In particular, integration of bodily signals within the peripersonal space (PPS) underlies the experience of the self in a body we own (self-identification) and that is experienced as occupying a specific location in space (self-location), two main components of bodily self-consciousness (BSC). Experiments investigating the effects of multisensory integration on BSC have typically employed supra-threshold sensory stimuli, neglecting the role of unconscious sensory signals in BSC, as tested in other consciousness research. Here, we used psychophysical techniques to test whether multisensory integration of bodily stimuli underlying BSC also occurs for multisensory inputs presented below the threshold of conscious perception. Our results indicate that visual stimuli rendered invisible through continuous flash suppression boost processing of tactile stimuli on the body (Exp. 1), and enhance the perception of near-threshold tactile stimuli (Exp. 2), only once they entered PPS. We then employed unconscious multisensory stimulation to manipulate BSC. Participants were presented with tactile stimulation on their body and with visual stimuli on a virtual body, seen at a distance, which were either visible or rendered invisible. We found that participants reported higher self-identification with the virtual body in the synchronous visuo-tactile stimulation (as compared to asynchronous stimulation; Exp. 3), and shifted their self-location toward the virtual body (Exp.4), even if stimuli were fully invisible. Our results indicate that multisensory inputs, even outside of awareness, are integrated and affect the phenomenological content of self-consciousness, grounding BSC firmly in the field of psychophysical consciousness studies.

N.F. was an EPFL fellow co-funded by Marie Skłodowska-Curie. C.L. was funded by the project ECSPLAIN (European Research Council under the Seventh Framework Programme, FPT/2007-2013, grant agreement no. 338866). A.A. was a Blavatnik fellow and a Royal society Kohn international fellow. We thank the Association for the Scientific Study of Consciousness for travel funding, and we are grateful to Liad Mudrik, Lavi Secundo, Andrés Canales-Johnson, and Ophelia Deroy for valuable discussions and helpful comments on the article.; International audience; Over the last 30 years, our understanding of the neurocognitive bases of consciousness has improved, mostly through studies employing vision. While studying consciousness in the visual modality presents clear advantages, we believe that a comprehensive scientific account of subjective experience must not neglect other exteroceptive and interoceptive signals as well as the role of multisensory interactions for perceptual and self-consciousness. Here, we briefly review four distinct lines of work which converge in documenting how multisensory signals are processed across several levels and contents of consciousness. Namely, how multisensory interactions occur when consciousness is prevented because of perceptual manipulations (i.e. subliminal stimuli) or because of low vigilance states (i.e. sleep, anesthesia), how interactions between exteroceptive and interoceptive signals give rise to bodily self-consciousness, and how multisensory signals are combined to form metacognitive judgments. By describing the interactions between multisensory signals at the perceptual, cognitive, and metacognitive levels, we illustrate how stepping out the visual comfort zone may help in deriving refined accounts of consciousness, and may allow cancelling out idiosyncrasies of each sense to delineate supramodal mechanisms involved during consciousness.

Exposure to Stressful Life Events (SLEs) has been linked to psychosis. However, the combined effect of SLEs and familial risk on subclinical psychotic symptoms over time remains unknown. The objective of the present study was to investigate the effect of SLEs on the level of subclinical psychotic symptoms in individuals with and without familial vulnerability for psychosis. Data were collected from siblings of individuals diagnosed with psychotic disorder and healthy controls at baseline (N = 293) and three years later at follow-up (N = 928). We assessed self-reported and observer-rated subclinical positive, negative, and depressive psychotic symptoms. Participants reported the number of SLEs in the preceding 6 months. A multilevel multivariate regression analysis revealed a positive association between the retrospectively assessed number of SLEs and symptom levels, regardless of vulnerability status (p

Objective: To examine the added value of a 9-week mindful yoga intervention (MYI) as add-on to treatment as usual (TAU) in reducing depression for young women (18–34 years) with major depressive disorder (MDD). Method: Randomized controlled trial (RCT; n = 171) comparing TAU + MYI with TAU-only. Assessments were at baseline, postintervention, and at 6- and 12-month follow-up. Primary outcome measures were clinician-rated and self-reported symptoms of depression, together with a diagnostic interview to establish MDD diagnosis that was restricted to the baseline and 12-month follow-up assessments. Quality of life in various domains was assessed as secondary outcome measure. As potential mediators for treatment efficacy, we included self-report measures of rumination, self-criticism, self-compassion, intolerance ofuncertainty, perceived body awareness and dispositional mindfulness, together with behavioral measures of attentional bias (AB) and depression-related self-associations. Results: Adding MYI to TAU did not lead to greater reduction of depression symptoms, lower rate of MDD diagnosis or increase in quality of life in various domains of functioning at post and follow-up assessments. There were no indirect effects through any of the potential mediators, with the exception of self-compassion. Conclusion: Adding MYI to TAU appeared not more efficacious than TAU-only in reducing depression symptoms in young women

It has been asserted that children with mathematics learning difficulties (MLD) constitute a heterogeneous group. To date, most researchers have investigated differences between predefined MLD subtypes. Specifically MLD children are frequently categorized a priori into groups based on the presence or absence of an additional disorder, such as a reading disorder, to examine cognitive differences between MLD subtypes. In the current study 226 third to six grade children (M age=131 months) with MLD completed a selection of number specific and general cognitive measures. The data driven approach was used to identify the extent to which performance of the MLD children on these measures could be clustered into distinct groups. In particular, after conducting a factor analysis, a 200 times repeated K-means clustering approach was used to classify the children's performance. Results revealed six distinguishable clusters of MLD children, specifically (a) a weak mental number line group, (b) weak ANS group, (c) spatial difficulties group, (d) access deficit group, (e) no numerical cognitive deficit group and (f) a garden-variety group. These findings imply that different cognitive subtypes of MLD exist and that these can be derived from data-driven approaches to classification. These findings strengthen the notion that MLD is a heterogeneous disorder, which has implications for the way in which intervention may be tailored for individuals within the different subtypes.

BACKGROUND: In Parkinson's disease (PD), neurophysiological abnormalities within the primary motor cortex (M1) have been shown to contribute to bradykinesia, but exact modalities are still uncertain. We propose that such motor slowness could involve alterations in mechanisms underlying movement preparation, especially the suppression of corticospinal excitability-called "preparatory suppression"-which is considered to propel movement execution by increasing motor neural gain in healthy individuals. METHODS: On two consecutive days, 29 PD patients (on and off medication) and 29 matched healthy controls (HCs) underwent transcranial magnetic stimulation over M1, eliciting motor-evoked potentials (MEPs) in targeted hand muscles, while they were either at rest or preparing a left- or right-hand response in an instructed-delay choice reaction time task. Preparatory suppression was assessed by expressing MEP amplitudes during movement preparation relative to rest. RESULTS: Contrary to HCs, PD patients showed a lack of preparatory suppression when the side of the responding hand was analyzed, especially when the latter was the most affected one. This deficit, which did not depend on dopamine medication, increased with disease duration and also tended to correlate with motor impairment, as measured by the Movement Disorder Society Unified Parkinson's Disease Rating Scale, Part III (both total and bradykinesia scores). CONCLUSIONS: Our novel findings indicate that preparatory suppression fades in PD, in parallel with worsening motor symptoms, including bradykinesia. Such results suggest that an alteration in this marker of intact movement preparation could indeed cause motor slowness and support its use in future studies on the relation between M1 alterations and motor impairment in PD. © 2022 International Parkinson and Movement Disorder Society.

Magnetic resonance imaging; Neurofilament light; Secondary progressive multiple sclerosis Imatge per ressonància magnètica; Llum del neurofilament; Esclerosi múltiple secundària progressiva Imagen por resonancia magnética; Luz de neurofilamento; Esclerosis múltiple secundaria progresiva Background: Cognitive impairment affects 50%–75% of people with secondary progressive multiple sclerosis (PwSPMS). Improving our ability to predict cognitive decline may facilitate earlier intervention. Objective: The main aim of this study was to assess the relationship between longitudinal changes in cognition and baseline serum neurofilament light chain (sNfL) in PwSPMS. In a multi-modal analysis, MRI variables were additionally included to determine if sNfL has predictive utility beyond that already established through MRI. Methods: Participants from the MS-STAT trial underwent a detailed neuropsychological test battery at baseline, 12 and 24 months. Linear mixed models were used to assess the relationships between cognition, sNfL, T2 lesion volume (T2LV) and normalised regional brain volumes. Results: Median age and Expanded Disability Status Score (EDSS) were 51 and 6.0. Each doubling of baseline sNfL was associated with a 0.010 [0.003–0.017] point per month faster decline in WASI Full Scale IQ Z-score (p = 0.008), independent of T2LV and normalised regional volumes. In contrast, lower baseline volume of the transverse temporal gyrus was associated with poorer current cognitive performance (0.362 [0.026–0.698] point reduction per mL, p = 0.035), but not change in cognition. The results were supported by secondary analyses on individual cognitive components. Conclusion: Elevated sNfL is associated with faster cognitive decline, independent of T2LV and regional normalised volumes. The author(s) disclosed receipt of the following financial support for the research, authorship and/or publication of this article: No specific funding was received for this research. T.W. is currently funded by the MS-STAT2 trial grant (NCT03387670). This is funded by the NIHR Health Technology Assessment (HTA) Programme, Multiple Sclerosis Society (UK) and the National Multiple Sclerosis Society (US).