Exploring the spatial resolution of TMS-EEG coupling on the sensorimotor region.

The use of TMS-EEG coupling as a neuroimaging tool for the functional exploration of the human brain recently gained strong interest. If this tool directly inherits the fine temporal resolution from EEG, its spatial counterpart remains unknown. In this study, we explored the spatial resolution of TMS-EEG coupling by evaluating the minimal distance between two stimulated cortical sites that would significantly evoke different response dynamics. TMS evoked responses were mapped on the sensorimotor region in twenty participants. The stimulation grid was composed of nine targets separated between 10 and 15 mm on average. The dynamical signatures of TMS evoked activity were extracted and compared between sites using both local and remote linear regression scores and spatial generalized mixed models. We found a significant effect of the distance between stimulated sites on their dynamical signatures, neighboring sites showing differentiable response dynamics. Besides, common dynamical signatures were also found between sites up to 25-30 mm from each other. This overlap in dynamical properties decreased with distance and was stronger between sites within the same Brodmann area. Our results suggest that the spatial resolution of TMS-EEG coupling might be at least as high as 10 mm. Furthermore, our results reveal an anisotropic spatial resolution that was higher across than within the same Brodmann areas, in accordance with the TMS induced E-field modeling. Common cytoarchitectonic leading to shared dynamical properties within the same Brodmann area could also explain this anisotropy. Overall, these findings suggest that TMS-EEG benefits from the spatial resolution of TMS, which makes it an accurate technique for meso-scale brain mapping.

Micro-pursuit: A class of fixational eye movements correlating with smooth, predictable, small-scale target trajectories.

Humans generate ocular pursuit movements when a moving target is tracked throughout the visual field. In this article, we show that pursuit can be generated and measured at small amplitudes, at the scale of fixational eye movements, and tag these eye movements as micro-pursuits. During micro-pursuits, gaze direction correlates with a target's smooth, predictable target trajectory. We measure similarity between gaze and target trajectories using a so-called maximally projected correlation and provide results in three experimental data sets. A first observation of micro-pursuit is provided in an implicit pursuit task, where observers were tasked to maintain their gaze fixed on a static cross at the center of screen, while reporting changes in perception of an ambiguous, moving (Necker) cube. We then provide two experimental paradigms and their corresponding data sets: a first replicating micro-pursuits in an explicit pursuit task, where observers had to follow a moving fixation cross (Cross), and a second with an unambiguous square (Square). Individual and group analyses provide evidence that micro-pursuits exist in both the Necker and Cross experiments but not in the Square experiment. The interexperiment analysis results suggest that the manipulation of stimulus target motion, task, and/or the nature of the stimulus may play a role in the generation of micro-pursuits.

Probing regional cortical excitability via input-output properties using transcranial magnetic stimulation and electroencephalography coupling.

The modular organization of the cortex refers to subsets of highly interconnected nodes, sharing specific cytoarchitectural and dynamical properties. These properties condition the level of excitability of local pools of neurons. In this study, we described TMS evoked potentials (TEP) input-output properties to provide new insights into regional cortical excitability. We combined robotized TMS with EEG to disentangle region-specific TEP from threshold to saturation and describe their oscillatory contents. Twenty-two young healthy participants received robotized TMS pulses over the right primary motor cortex (M1), the right dorsolateral prefrontal cortex (DLPFC) and the right superior occipital lobe (SOL) at five stimulation intensities (40, 60, 80, 100, and 120% resting motor threshold) and one short-interval intracortical inhibition condition during EEG recordings. Ten additional subjects underwent the same experiment with a realistic sham TMS procedure. The results revealed interregional differences in the TEPs input-output functions as well as in the responses to paired-pulse conditioning protocols, when considering early local components (<80 ms). Each intensity in the three regions was associated with complex patterns of oscillatory activities. The quality of the regression of TEPs over stimulation intensity was used to derive a new readout for cortical excitability and dynamical properties, revealing lower excitability in the DLPFC, followed by SOL and M1. The realistic sham experiment confirmed that these early local components were not contaminated by multisensory stimulations. This study provides an entirely new analytic framework to characterize input-output relations throughout the cortex, paving the way to a more accurate definition of local cortical excitability.

Of guns and snakes: testing a modern threat superiority effect.

Previous studies suggest that ancient (i.e. evolutionary-based) threats capture attention because human beings possess an inborn module shaped by evolution and dedicated to their detection. An alternative account proposes that a key feature predicting whether a stimulus will capture attention is its relevance rather than its ontology (i.e. phylogenetic or ontogenetic threat). Within this framework, the present research deals with the attentional capture by threats commonly encountered in our urban environment. In two experiments, we investigate the attentional capture by modern threats (i.e. weapons). In Experiment 1, participants responded to a target preceded by a cue, which was a weapon or a non-threatening stimulus. We found a larger cuing effect (faster reaction times to valid vs. invalid trials) with weapons as compared with non-threatening cues. In Experiment 2, modern (e.g. weapons) and ancient threats (e.g. snakes) were pitted against one another as cues to determine which ones preferentially capture attention. Crucially, participants were faster to detect a target preceded by a modern as opposed to an ancient threat, providing initial evidence for a superiority of modern threat. Overall, the present findings appear more consistent with a relevance-based explanation rather than an evolutionary-based explanation of threat detection.

Mapping dynamical properties of cortical microcircuits using robotized TMS and EEG: Towards functional cytoarchitectonics.

Brain dynamics at rest depend on the large-scale interactions between oscillating cortical microcircuits arranged into macrocolumns. Cytoarchitectonic studies have shown that the structure of those microcircuits differs between cortical regions, but very little is known about interregional differences of their intrinsic dynamics at a macro-scale in human. We developed here a new method aiming at mapping the dynamical properties of cortical microcircuits non-invasively using the coupling between robotized transcranial magnetic stimulation and electroencephalography. We recorded the responses evoked by the stimulation of 18 cortical targets largely covering the accessible neocortex in 22 healthy volunteers. Specific data processing methods were developed to map the local source activity of each cortical target, which showed inter-regional differences with very good interhemispheric reproducibility. Functional signatures of cortical microcircuits were further studied using spatio-temporal decomposition of local source activities in order to highlight principal brain modes. The identified brain modes revealed that cortical areas with similar intrinsic dynamical properties could be distributed either locally or not, with a spatial signature that was somewhat reminiscent of resting state networks. Our results provide the proof of concept of "functional cytoarchitectonics", that would guide the parcellation of the human cortex using not only its cytoarchitecture but also its intrinsic responses to local perturbations. This opens new avenues for brain modelling and physiopathology readouts.

Spatial frequency processing in scene-selective cortical regions.

Visual analysis begins with the parallel extraction of different attributes at different spatial frequencies. Low spatial frequencies (LSF) convey coarse information and are characterized by high luminance contrast, while high spatial frequencies (HSF) convey fine details and are characterized by low luminance contrast. In the present fMRI study, we examined how scene-selective regions-the parahippocampal place area (PPA), the retrosplenial cortex (RSC) and the occipital place area (OPA)-responded to spatial frequencies when contrast was either equalized or not equalized across spatial frequencies. Participants performed a categorization task on LSF, HSF and non-filtered scenes belonging to two different categories (indoors and outdoors). We either left contrast across scenes untouched, or equalized it using a root-mean-square contrast normalization. We found that when contrast remained unmodified, LSF and NF scenes elicited greater activation than HSF scenes in the PPA. However, when contrast was equalized across spatial frequencies, the PPA was selective to HFS. This suggests that PPA activity relies on an interaction between spatial frequency and contrast in scenes. In the RSC, LSF and NF elicited greater response than HSF scenes when contrast was not modified, while no effect of spatial frequencies appeared when contrast was equalized across filtered scenes, suggesting that the RSC is sensitive to high-contrast information. Finally, we observed selective activation of the OPA in response to HSF, irrespective of contrast manipulation. These results provide new insights into how scene-selective areas operate during scene processing.

Effective connectivity in the neural network underlying coarse-to-fine categorization of visual scenes. A dynamic causal modeling study.

According to current models of visual perception scenes are processed in terms of spatial frequencies following a predominantly coarse-to-fine processing sequence. Low spatial frequencies (LSF) reach high-order areas rapidly in order to activate plausible interpretations of the visual input. This triggers top-down facilitation that guides subsequent processing of high spatial frequencies (HSF) in lower-level areas such as the inferotemporal and occipital cortices. However, dynamic interactions underlying top-down influences on the occipital cortex have never been systematically investigated. The present fMRI study aimed to further explore the neural bases and effective connectivity underlying coarse-to-fine processing of scenes, particularly the role of the occipital cortex. We used sequences of six filtered scenes as stimuli depicting coarse-to-fine or fine-to-coarse processing of scenes. Participants performed a categorization task on these stimuli (indoor vs. outdoor). Firstly, we showed that coarse-to-fine (compared to fine-to-coarse) sequences elicited stronger activation in the inferior frontal gyrus (in the orbitofrontal cortex), the inferotemporal cortex (in the fusiform and parahippocampal gyri), and the occipital cortex (in the cuneus). Dynamic causal modeling (DCM) was then used to infer effective connectivity between these regions. DCM results revealed that coarse-to-fine processing resulted in increased connectivity from the occipital cortex to the inferior frontal gyrus and from the inferior frontal gyrus to the inferotemporal cortex. Critically, we also observed an increase in connectivity strength from the inferior frontal gyrus to the occipital cortex, suggesting that top-down influences from frontal areas may guide processing of incoming signals. The present results support current models of visual perception and refine them by emphasizing the role of the occipital cortex as a cortical site for feedback projections in the neural network underlying coarse-to-fine processing of scenes.

Coarse-to-fine categorization of visual scenes in scene-selective cortex.

Neurophysiological, behavioral, and computational data indicate that visual analysis may start with the parallel extraction of different elementary attributes at different spatial frequencies and follows a predominantly coarse-to-fine (CtF) processing sequence (low spatial frequencies [LSF] are extracted first, followed by high spatial frequencies [HSF]). Evidence for CtF processing within scene-selective cortical regions is, however, still lacking. In the present fMRI study, we tested whether such processing occurs in three scene-selective cortical regions: the parahippocampal place area (PPA), the retrosplenial cortex, and the occipital place area. Fourteen participants were subjected to functional scans during which they performed a categorization task of indoor versus outdoor scenes using dynamic scene stimuli. Dynamic scenes were composed of six filtered images of the same scene, from LSF to HSF or from HSF to LSF, allowing us to mimic a CtF or the reverse fine-to-coarse (FtC) sequence. Results showed that only the PPA was more activated for CtF than FtC sequences. Equivalent activations were observed for both sequences in the retrosplenial cortex and occipital place area. This study suggests for the first time that CtF sequence processing constitutes the predominant strategy for scene categorization in the PPA.

Microsaccades are modulated by both attentional demands of a visual discrimination task and background noise.

Microsaccades are miniature saccades occurring once or twice per second during visual fixation. While microsaccades and saccades share similarities at the oculomotor level, the functional roles of microsaccades are still debated. In this study, we examined the hypothesis that the microsaccadic activity is affected by the type of noisy background during the execution of a particular discrimination task. Human subjects had to judge the orientation of a tilted stimulus embedded in static or dynamic backgrounds in a forced choice-task paradigm, as adapted from Rucci, Iovin, Poletti, and Santini (2007). Static backgrounds induced more microsaccades than dynamic ones only during the execution of the discrimination task. A directional bias of microsaccades, dictated by the stimulus orientation, was temporally coupled with this period of increased activity. Both microsaccade rates and orientations were comparable across background types after the response time although subjects maintained fixation until the end of the trial. This represents a background-specific modulation of the microsaccadic activity driven by attentional demands. The visual influence of microsaccades on discrimination performances was modeled at the retinal level for both types of backgrounds. A higher simulated microsaccadic activity was necessary for static backgrounds in order to achieve discrimination performance scores comparable to that of dynamic ones. Taken together, our experimental and theoretical findings further support the idea that microsaccades are under attentional control and represent an efficient sampling strategy allowing spatial information acquisition.

Multi-scale and cross-dimensional TMS mapping: A proof of principle in patients with Parkinson's disease and deep brain stimulation.

Introduction: Transcranial magnetic stimulation (TMS) mapping has become a critical tool for exploratory studies of the human corticomotor (M1) organization. Here, we propose to gather existing cutting-edge TMS-EMG and TMS-EEG approaches into a combined multi-dimensional TMS mapping that considers local and whole-brain excitability changes as well as state and time-specific changes in cortical activity. We applied this multi-dimensional TMS mapping approach to patients with Parkinson's disease (PD) with Deep brain stimulation (DBS) of the sub-thalamic nucleus (STN) ON and OFF. Our goal was to identifying one or several TMS mapping-derived markers that could provide unprecedent new insights onto the mechanisms of DBS in movement disorders. Methods: Six PD patients (1 female, mean age: 62.5 yo [59-65]) implanted with DBS-STN for 1 year, underwent a robotized sulcus-shaped TMS motor mapping to measure changes in muscle-specific corticomotor representations and a movement initiation task to probe state-dependent modulations of corticospinal excitability in the ON (using clinically relevant DBS parameters) and OFF DBS states. Cortical excitability and evoked dynamics of three cortical areas involved in the neural control of voluntary movements (M1, pre-supplementary motor area - preSMA and inferior frontal gyrus - IFG) were then mapped using TMS-EEG coupling in the ON and OFF state. Lastly, we investigated the timing and nature of the STN-to-M1 inputs using a paired pulse DBS-TMS-EEG protocol. Results: In our sample of patients, DBS appeared to induce fast within-area somatotopic re-arrangements of motor finger representations in M1, as revealed by mediolateral shifts of corticomuscle representations. STN-DBS improved reaction times while up-regulating corticospinal excitability, especially during endogenous motor preparation. Evoked dynamics revealed marked increases in inhibitory circuits in the IFG and M1 with DBS ON. Finally, inhibitory conditioning effects of STN single pulses on corticomotor activity were found at timings relevant for the activation of inhibitory GABAergic receptors (4 and 20 ms). Conclusion: Taken together, these results suggest a predominant role of some markers in explaining beneficial DBS effects, such as a context-dependent modulation of corticospinal excitability and the recruitment of distinct inhibitory circuits, involving long-range projections from higher level motor centers and local GABAergic neuronal populations. These combined measures might help to identify discriminative features of DBS mechanisms towards deep clinical phenotyping of DBS effects in Parkinson's Disease and in other pathological conditions.

Augmented-Feedback Training Improves Cognitive Motor Performance of Soccer Players.

PURPOSE: In this study, we tested the hypothesis that augmented feedback (AF) training can improve both perceptual-cognitive and/or motor skills specific to soccer. METHODS: Three groups of young elite players (U14-U15 categories) performed a test consisting in passing the ball as accurately and as quickly as possible toward a visual target moving briefly across a large screen located at 6 m from the player. The performed task required players to correctly perceive the target, anticipate its future location, and to adequately adjust the pass direction and power. The control group (CON) performed normal soccer training and was compared with two visuomotor training groups (AF and no-feedback [NF]) that followed the same training regime but integrated series of 32 passes three times per week over a 17-d period into their normal soccer training. Objective measurements of the passing performance were provided using a high-technology system (COGNIFOOT) before, during, and after training. During training, only players of the AF group received visuoauditory feedback immediately after each trial informing them about the accuracy of their passes. RESULTS: The results show that only players of the AF group significantly improved passing accuracy, reactiveness, and global passing performance (+22%), whereas the NF group only improved passing accuracy. None of these parameters was improved in the CON group. The objectively measured changes in passing performance were compared with the more subjectively judged passing performance provided by coaches and players. Coaches' judgments were more reliable than players' judgments and exhibited a training group effect comparable to the ones objectively measured by COGNIFOOT. CONCLUSIONS: This study provides evidence that the training of cognitive motor performance in soccer players highly benefits from the use of augmented feedback.

Face perception influences the programming of eye movements.

Previous studies have shown that face stimuli elicit extremely fast and involuntary saccadic responses toward them, relative to other categories of visual stimuli. In the present study, we further investigated to what extent face stimuli influence the programming and execution of saccades examining their amplitude. We performed two experiments using a saccadic choice task: two images (one with a face, one with a vehicle) were simultaneously displayed in the left and right visual fields of participants who had to initiate a saccade toward the image (Experiment 1) or toward a cross in the image (Experiment 2) containing a target stimulus (a face or a vehicle). Results revealed shorter saccades toward vehicle than face targets, even if participants were explicitly asked to perform their saccades toward a specific location (Experiment 2). Furthermore, error saccades had smaller amplitude than correct saccades. Further analyses showed that error saccades were interrupted in mid-flight to initiate a concurrently-programmed corrective saccade. Overall, these data suggest that the content of visual stimuli can influence the programming of saccade amplitude, and that efficient online correction of saccades can be performed during the saccadic choice task.

The importance of recurrent top-down synaptic connections for the anticipation of dynamic emotions.

Different studies have shown the efficiency of a feed-forward neural network in categorizing basic emotional facial expressions. However, recent findings in psychology and cognitive neuroscience suggest that visual recognition is not a pure bottom-up process but likely involves top-down recurrent connectivity. In the present computational study, we compared the performances of a pure bottom-up neural network (a standard multi-layer perceptron, MLP) with a neural network involving recurrent top-down connections (a simple recurrent network, SRN) in the anticipation of emotional expressions. In two complementary simulations, results revealed that the SRN outperformed the MLP for ambiguous intensities in the temporal sequence, when the emotions were not fully depicted but when sufficient contextual information (related to previous time frames) was provided. Taken together, these results suggest that, despite the cost of recurrent connections in terms of energy and processing time for biological organisms, they can provide a substantial advantage for the fast recognition of uncertain visual signals.

Twice-daily neuronavigated intermittent theta burst stimulation for bipolar depression: A Randomized Sham-Controlled Pilot Study.

The safety and efficacy of neuronavigated intermittent theta burst stimulation (iTBS) in patients with bipolar depression has not yet been investigated. We hypothesized the superiority of active iTBS over sham. Twenty-six patients were randomly allocated to receive either active (n=12) or sham (n=14) iTBS. Response and remission rates according to changes in depression MADRS score were high following active iTBS (72% and 42% for response and remission rates, respectively), but no significant difference was found after sham stimulation (42%and 25%). No adverse events were observed. This study revealed the safety and tolerability of twice daily iTBS in patients with bipolar depression. Larger controlled studies are warranted to prove iTBS superiority in treatment-resistant bipolar depression.

Early Emotional Attention is Impacted in Alzheimer's Disease: An Eye-Tracking Study.

Emotional deficits have been repetitively reported in Alzheimer's disease (AD) without clearly identifying how emotional processing is impaired in this pathology. This paper describes an investigation of early emotional processing, as measured by the effects of emotional visual stimuli on a saccadic task involving both pro (PS) and anti (AS) saccades. Sixteen patients with AD and 25 age-matched healthy controls were eye-tracked while they had to quickly move their gaze toward a positive, negative, or neutral image presented on a computer screen (in the PS condition) or away from the image (in the AS condition). The age-matched controls made more AS mistakes for negative stimuli than for other stimuli, and triggered PSs toward negative stimuli more quickly than toward other stimuli. In contrast, patients with AD showed no difference with regard to the emotional category in any of the tasks. The present study is the first to highlight a lack of early emotional attention in patients with AD. These results should be taken into account in the care provided to patients with AD, since this early impairment might seriously degrade their overall emotional functioning.

Do low spatial frequencies explain the extremely fast saccades towards human faces?

The visual perception of human faces by man is fast and efficient compared to that of other categories of objects. Using a saccadic choice task, recent studies showed that participants were able to initiate fast reliable saccades in just 100-110ms toward an image of a human face, when this was presented alongside another image without a face. This extremely fast saccadic reaction time is barely predicted using classical models of visual perception. Thus, the present research investigates whether this result might be explained by the low spatial frequency content of images. Using the same paradigm, with two images simultaneously presented to the left or right visual fields, participants were asked to make a saccade towards a target image. The target was defined as an image belonging to one category: human face, animal or vehicle. The other image corresponded to the distractor and belongs to the other categories. We compared performance to saccade toward one category of target. The two images were displayed either in color, gray-level, low-pass filtered or high-pass filtered. As previous studies, we found that the shortest SRT was observed for saccades towards faces rather than towards animals or vehicles. Analysis of saccadic reaction time distributions showed that, in 130-140ms, participants were able to make more correct than incorrect saccades towards faces for unfiltered (color and gray-level) and low-pass filtered images whereas they needed more time for high-pass filtered images. In contrast, the minimum time participants needed to correctly saccade towards animals and vehicles was longer for low-pass and high-pass filtered than for unfiltered images. The analysis of the image statistics in the Fourier domain revealed that the amplitude spectrum of faces was mainly contained in the low spatial frequencies. Consistent with a coarse-to-fine processing of visual information, our results suggest that extremely fast saccades towards faces could be initiated by low spatial frequencies.

Effects of age on the soccer-specific cognitive-motor performance of elite young soccer players: Comparison between objective measurements and coaches' evaluation.

The cognitive-motor performance (CMP), defined here as the capacity to rapidly use sensory information and transfer it into efficient motor output, represents a major contributor to performance in almost all sports, including soccer. Here, we used a high-technology system (COGNIFOOT) which combines a visual environment simulator fully synchronized with a motion capture system. This system allowed us to measure objective real-time CMP parameters (passing accuracy/speed and response times) in a large turf-artificial grass playfield. Forty-six (46) young elite soccer players (including 2 female players) aged between 11 and 16 years who belonged to the same youth soccer academy were tested. Each player had to pass the ball as fast and as accurately as possible towards visual targets projected onto a large screen located 5.32 meters in front of him (a short pass situation). We observed a linear age-related increase in the CMP: the passing accuracy, speed and reactiveness of players improved by 4 centimeters, 2.3 km/h and 30 milliseconds per year of age, respectively. These data were converted into 5 point-scales and compared to the judgement of expert coaches, who also used a 5 point-scale to evaluate the same CMP parameters but based on their experience with the players during games and training. The objectively-measured age-related CMP changes were also observed in expert coaches' judgments although these were more variable across coaches and age categories. This demonstrates that high-technology systems like COGNIFOOT can be used in complement to traditional approaches of talent identification and to objectively monitor the progress of soccer players throughout a cognitive-motor training cycle.

Accurate statistical tests for smooth classification images.

Despite an obvious demand for a variety of statistical tests adapted to classification images, few have been proposed. We argue that two statistical tests based on random field theory (RFT) satisfy this need for smooth classification images. We illustrate these tests on classification images representative of the literature from F. Gosselin and P. G. Schyns (2001) and from A. B. Sekuler, C. M. Gaspar, J. M. Gold, and P. J. Bennett (2004). The necessary computations are performed using the Stat4Ci Matlab toolbox.

Rapid scene categorization: role of spatial frequency order, accumulation mode and luminance contrast.

Visual analysis follows a default, predominantly coarse-to-fine processing sequence. Low spatial frequencies (LSF) are processed more rapidly than high spatial frequencies (HSF), allowing an initial coarse parsing of visual input, prior to analysis of finer information. Our study investigated the influence of spatial frequency processing order, accumulation mode (i.e. how spatial frequency information is received as an input by the visual system, throughout processing), and differences in luminance contrast between spatial frequencies on rapid scene categorization. In Experiment 1, we used sequences composed of six filtered scenes, assembled from LSF to HSF (coarse-to-fine) or from HSF to LSF (fine-to-coarse) to test the effects of spatial frequency order. Spatial frequencies were either successive or additive within sequences to test the effects of spatial frequency accumulation mode. Results showed that participants categorized coarse-to-fine sequences more rapidly than fine-to-coarse sequences, irrespective of spatial frequency accumulation in the sequences. In Experiment 2, we investigated the extent to which differences in luminance contrast rather than in spatial frequency account for the advantage of coarse-to-fine over fine-to-coarse processing. Results showed that both spatial frequencies and luminance contrast account for a predominant coarse-to-fine processing, but that the coarse-to-fine advantage stems mainly from differences in spatial frequencies. Our study cautions against the use of contrast normalization in studies investigating spatial frequency processing. We argue that this type of experimental manipulation can impair the intrinsic properties of a visual stimulus. As the visual system relies on these to enable recognition, bias may be induced in strategies of visual analysis.