Multisensory integration deficits in Schizophrenia and Autism evidenced in behaviour but not event related potentials.

The process of integrating information from different sensory channels, known as multisensory integration (MSI) was assessed in two disorders, Autism Spectrum Disorder (ASD) and Schizophrenia (SCZ). 32 healthy controls (HC), 35 SCZ patients, and 23 ASD patients performed an audiovisual (AV) synchronous target detection task while reaction time (RT) and scalp recorded electrophysiological (EEG) activity were measured. MSI in the AV condition resulted in faster and less variable RTs compared to the unimodal conditions. Using our novel bootstrap method, MSI gain was observed in 78 % of HC, 26 % of ASD, and 48 % of SCZ patients. At the neural level, MSI in the AV condition resulted in larger amplitude of sensory evoked responses and cognitive P3 response compared to the corresponding unimodal conditions. These neural effects of MSI were not related to the behavioural MSI gain identified at the individual level and could not explain the deficits in behavioural MSI of patient groups. In conclusion, a robust MSI gain deficit in RT was observed in both patient groups that was not reflected in early perceptual and cognitive electro-cortical responses, suggesting that behavioural MSI deficits in ASD and SCZ may arise at late processing stages such as response selection.

Smartwatch digital phenotypes predict positive and negative symptom variation in a longitudinal monitoring study of patients with psychotic disorders.

Introduction: Monitoring biometric data using smartwatches (digital phenotypes) provides a novel approach for quantifying behavior in patients with psychiatric disorders. We tested whether such digital phenotypes predict changes in psychopathology of patients with psychotic disorders. Methods: We continuously monitored digital phenotypes from 35 patients (20 with schizophrenia and 15 with bipolar spectrum disorders) using a commercial smartwatch for a period of up to 14 months. These included 5-min measures of total motor activity from an accelerometer (TMA), average Heart Rate (HRA) and heart rate variability (HRV) from a plethysmography-based sensor, walking activity (WA) measured as number of total steps per day and sleep/wake ratio (SWR). A self-reporting questionnaire (IPAQ) assessed weekly physical activity. After pooling phenotype data, their monthly mean and variance was correlated within each patient with psychopathology scores (PANSS) assessed monthly. Results: Our results indicate that increased HRA during wakefulness and sleep correlated with increases in positive psychopathology. Besides, decreased HRV and increase in its monthly variance correlated with increases in negative psychopathology. Self-reported physical activity did not correlate with changes in psychopathology. These effects were independent from demographic and clinical variables as well as changes in antipsychotic medication dose. Discussion: Our findings suggest that distinct digital phenotypes derived passively from a smartwatch can predict variations in positive and negative dimensions of psychopathology of patients with psychotic disorders, over time, providing ground evidence for their potential clinical use.

E-Prevention: Advanced Support System for Monitoring and Relapse Prevention in Patients with Psychotic Disorders Analyzing Long-Term Multimodal Data from Wearables and Video Captures.

Wearable technologies and digital phenotyping foster unique opportunities for designing novel intelligent electronic services that can address various well-being issues in patients with mental disorders (i.e., schizophrenia and bipolar disorder), thus having the potential to revolutionize psychiatry and its clinical practice. In this paper, we present e-Prevention, an innovative integrated system for medical support that facilitates effective monitoring and relapse prevention in patients with mental disorders. The technologies offered through e-Prevention include: (i) long-term continuous recording of biometric and behavioral indices through a smartwatch; (ii) video recordings of patients while being interviewed by a clinician, using a tablet; (iii) automatic and systematic storage of these data in a dedicated Cloud server and; (iv) the ability of relapse detection and prediction. This paper focuses on the description of the e-Prevention system and the methodologies developed for the identification of feature representations that correlate with and can predict psychopathology and relapses in patients with mental disorders. Specifically, we tackle the problem of relapse detection and prediction using Machine and Deep Learning techniques on all collected data. The results are promising, indicating that such predictions could be made and leading eventually to the prediction of psychopathology and the prevention of relapses.

Independent sources of anisotropy in visual orientation representation: a visual and a cognitive oblique effect.

The representation of visual orientation is more accurate for cardinal orientations compared to oblique, and this anisotropy has been hypothesized to reflect a low-level visual process (visual, "class 1" oblique effect). The reproduction of directional and orientation information also leads to a mean error away from cardinal orientations or directions. This anisotropy has been hypothesized to reflect a high-level cognitive process of space categorization (cognitive, "class 2," oblique effect). This space categorization process would be more prominent when the visual representation of orientation degrades such as in the case of working memory with increasing cognitive load, leading to increasing magnitude of the "class 2" oblique effect, while the "class 1" oblique effect would remain unchanged. Two experiments were performed in which an array of orientation stimuli (1-4 items) was presented and then subjects had to realign a probe stimulus within the previously presented array. In the first experiment, the delay between stimulus presentation and probe varied, while in the second experiment, the stimulus presentation time varied. The variable error was larger for oblique compared to cardinal orientations in both experiments reproducing the visual "class 1" oblique effect. The mean error also reproduced the tendency away from cardinal and toward the oblique orientations in both experiments (cognitive "class 2" oblique effect). The accuracy or the reproduced orientation degraded (increasing variable error) and the cognitive "class 2" oblique effect increased with increasing memory load (number of items) in both experiments and presentation time in the second experiment. In contrast, the visual "class 1" oblique effect was not significantly modulated by any one of these experimental factors. These results confirmed the theoretical predictions for the two anisotropies in visual orientation reproduction and provided support for models proposing the categorization of orientation in visual working memory.

Two independent sources of anisotropy in the visual representation of direction in 2-D space.

It is known that visual direction representation is more accurate for cardinal directions compared to oblique, a phenomenon named the "oblique effect". It has been hypothesized that there are two sources of oblique effect, a low level one confined to vision and a high level one extending to different modalities and corresponding to higher cognitive processes. In this study directional error (DE) was measured when normal individuals tried to align the direction of an arrow presented in the center of a computer monitor to the direction of a peripheral target located in one of 32 directions equally spaced on an imaginary circle of 60 mm radius. Task difficulty was manipulated by varying arrow length (15, 30, 45 and 60 mm). By measuring mean DE and its variance we identified two independent sources of the oblique effect. A low level oblique effect was manifested in higher accuracy or equivalently lower variance of DE in the alignment for cardinal orientations compared to oblique. A second oblique effect was manifested measuring mean DE resulting in space expansion in the vicinity of cardinal directions and space contraction in the vicinity of oblique directions. Only this latter source of oblique effect was modulated by arrow length as predicted from a theoretical model postulating that this oblique effect is produced by a cognitive process of 2-D space categorization.

Increased intra-subject reaction time variability in the volitional control of movement in schizophrenia.

Increased Reaction Time (RT) studies intra-subject variability is an emerging and consistent finding in RT studies of schizophrenia. A group of 23 patients suffering from DSM-IV schizophrenia and a group of 23 age-matched control subjects performed two RT tasks requiring basic sensorimotor processing and engaging two different motor systems: the Finger Lift Reaction Time task and the Voluntary Saccade Reaction Time task. The Ex-Gaussian model was applied to the RT distributions measuring the mean (mu), and standard deviation (sigma) of a Gaussian component thought to reflect sensorimotor processing and an exponential component (tau), thought to reflect an intermediate decision process. In both tasks, a significantly larger RT intra-subject variability effectively dissociated patients from controls. RT intra-subject variability in the two tasks was highly correlated only for patients. Both sigma and tau were significantly higher in the patient group with tau being the best predictor of schizophrenia. Furthermore, only in the patient group were sigma and tau highly correlated between the two tasks. The results reflect a deficit in information processing that may not be confined to decision processes related to the frontal cortex; rather, they may indicate dysfunction in distributed neural networks modulating adaptive regulation of performance.

Event-related potentials before saccades and antisaccades and their relation to reaction time.

In the present study, reaction time (RT) was measured in 12 healthy subjects in a saccade and antisaccade task while recording electroencephalographic activity (EEG) from 62 electrodes on the scalp. Event-related potentials averaged both on target appearance and on saccade onset were larger in amplitude (increased negativity) for the antisaccade task compared to the saccade task. The relation of RT variability to EEG amplitude was studied by averaging stimulus-aligned and movement-aligned individual trials for each subject into four RT quartile groups. The analysis showed a relation of EEG amplitude to RT for both saccades and antisaccades. More specifically, the ERP negativity at 100-120 ms after stimulus onset in the saccade task and at 160-200 ms after stimulus onset in the antisaccade task for stimulus-aligned ERPs decreased monotonically with increasing RT as would be expected if this signal would be related to the eye movement preparation processes. This was much more pronounced and wide spread for the antisaccades than for visually triggered saccades. The peak negativity before movement onset for movement-aligned ERPs also covaried with RT suggesting no relation of this activity to movement preparation processes. This study then confirmed that only a particular ERP signal variation was related to the saccadic eye movement preparatory processes while other components of the ERP have no specific relation to the movement preparation. This particular signal was more prominent for antisaccades compared to visually triggered saccades supporting previous evidence for the cortical involvement in the preparation of these voluntary eye movements. In conclusion, this study validates the use of ERPs in the study of the planning and execution of saccadic eye movements.

Memory pointing in children and adults: dissociations in the maturation of spatial and temporal movement parameters.

In previous studies a systematic directional error (the "motor oblique effect") was found in 2D memory pointing movements of healthy adults. In this study we extend these observations to observe that healthy children displayed the same motor oblique effect. In contrast other spatial and temporal movement parameters (mean amplitude error, square directional and amplitude error, latency and the time to maximum velocity) changed with increasing age. Memory delay increased the square directional and amplitude error independent of age. Finally failure of movement inhibition during the delay was more frequent in children compared to adults. These results favor the hypothesis that the motor oblique effect related to perceptual processing biases is constant from childhood while other movement parameters are modulated by age reflecting the continuing optimization of motor control from childhood to adulthood. The dissociation of memory and age effects suggests that motor working memory is already mature in young children.

Larger variability of saccadic reaction times in schizophrenia patients.

Slower mean reaction time (RT), known as psychomotor slowing, is well documented in patients with schizophrenia. Fewer studies have shown increased variability of RT in these patients suggesting a basic difference in the distribution of RT. In this study median RT and its variability were measured for visually guided saccades performed by 53 patients and 1089 control subjects. Then average cumulative RT distributions were derived for each group and the RT distribution for each group was modeled using a decision signal rising linearly to a threshold signaling the beginning of the visually guided saccade. There was a small increase in the median RT for patients while their RTs were much more variable from trial to trial leading to a difference in the average RT distribution of the patient group. The model application led to the conclusion that this difference in the distribution of RT for patients could be attributed to a basic difference in information processing leading to the decision to move the eyes to the visually presented target. This information-processing difference could be the result of a difference in the build-up of neuronal activity involved in the generation of visually guided saccades in the frontal cortex.

Arm movement metrics influence saccade metrics when looking and pointing towards a memorized target location.

Saccades are known to influence subsequent arm movements. There is less information to suggest that the characteristics of saccades depend on the reaching movements they accompany. To explore this issue, we studied the systematic errors of saccades generated by two adult female Rhesus monkeys (Macaca Mulata), which were trained to perform center-out saccades and reaching arm movements to the memorized location of targets. The mean error of saccades executed in isolation differed significantly from that of saccades that were executed towards the same target location and accompanied a reaching movement. This difference was observed in both animals whether they used their right or left arm, whether the size of the movement was equal to 10 or 15 degrees and whether there was no delay or a 3 s delay between the extinction of a visual target and the cue to move. Moreover, the endpoints of saccades and those of the arm-reaching movements in the reaching task were significantly correlated. These data suggest that signals specifying the metrics of limb movements influence those specifying the metrics of preceding saccades at a programming stage.

Perception action interaction: the oblique effect in the evolving trajectory of arm pointing movements.

In previous studies, we provided evidence for a directional distortion of the endpoints of movements to memorized target locations. This distortion was similar to a perceptual distortion in direction discrimination known as the oblique effect so we named it the "motor oblique effect". In this report we analyzed the directional errors during the evolution of the movement trajectory in memory guided and visually guided pointing movements and compared them with directional errors in a perceptual experiment of arrow pointing. We observed that the motor oblique effect was present in the evolving trajectory of both memory and visually guided reaching movements. In memory guided pointing the motor oblique effect did not disappear during trajectory evolution while in visually guided pointing the motor oblique effect disappeared with decreasing distance from the target and was smaller in magnitude compared to the perceptual oblique effect and the memory motor oblique effect early on after movement initiation. The motor oblique effect in visually guided pointing increased when reaction time was small and disappeared with larger reaction times. The results are best explained using the hypothesis that a low level oblique effect is present for visually guided pointing movements and this effect is corrected by a mechanism that does not depend on visual feedback from the trajectory evolution and might even be completed during movement planning. A second cognitive oblique effect is added in the perceptual estimation of direction and affects the memory guided pointing movements. It is finally argued that the motor oblique effect can be a useful probe for the study of perception-action interaction.

"Motor oblique effect": perceptual direction discrimination and pointing to memorized visual targets share the same preference for cardinal orientations.

In previous studies we observed a pattern of systematic directional errors when humans pointed to memorized visual target locations in two-dimensional (2-D) space. This directional error was also observed in the initial direction of slow movements toward visual targets or movements to kinesthetically defined targets in 2-D space. In this study we used a perceptual experiment where subjects decide whether an arrow points in the direction of a visual target in 2-D space and observed a systematic distortion in direction discrimination known as the "oblique effect." More specifically, direction discrimination was better for cardinal directions than for oblique. We then used an equivalent measure of direction discrimination in a task where subjects pointed to memorized visual target locations and showed the presence of a motor oblique effect. We finally modeled the oblique effect in the perceptual and motor task using a quadratic function. The model successfully predicted the observed direction discrimination differences in both tasks and, furthermore, the parameter of the model that was related to the shape of the function was not different between the motor and the perceptual tasks. We conclude that a similarly distorted representation of target direction is present for memorized pointing movements and perceptual direction discrimination.

Smooth pursuit eye movements in 1,087 men: effects of schizotypy, anxiety, and depression.

Individuals with schizotypal personality disorder or high scores in questionnaires measuring schizotypy are at high risk for the development of schizophrenia and they also share some of the same phenotypic characteristics such as eye-tracking dysfunction (ETD). The question arises whether these individuals form a distinct high-risk group in the general population or whether schizotypy and ETD co-vary in the general population with no distinct cutoff point for a high-risk group. A large sample of military conscripts aged 18-25 were screened using oculomotor, cognitive and psychometric tools for the purposes of a prospective study on predisposing factors for the development of psychosis. Schizotypy measured using the perceptual aberration scale (PAS) and the schizotypal personality questionnaire (SPQ), anxiety and depression, measured using the Symptom Checklist 90-R, had no effect on pursuit performance in the total sample. Small groups of individuals with very high scores in schizotypy questionnaires were then identified. These groups were not mutually exclusive. The high PAS group had higher root-mean-square error scores (a quantitative measure for pursuit quality) than the total sample, and the high disorganized factor of SPQ group had lower gain and higher saccade frequencies in pursuit than the total sample. The presence of significant differences in pursuit performance only for predefined high schizotypy groups favors the hypothesis that individuals with high schizotypy might present one or more high-risk groups, distinct from the general population, that are prone to ETD as that observed in schizophrenia.

Parallel processing of spatial and serial order information before moving to a remembered target.

Information storage and retrieval from working memory is limited by the capacity of storage mechanisms and attentional processes. Nevertheless, it has been shown that processing of multiple features can proceed independently in working memory. In this study we investigated how serial order and directional information are processed when executing a movement to a remembered target direction. We compared the performance of 11 healthy subjects in 3 motor working memory tasks, one with a varying spatial memory load, one with a varying serial order memory load, and one in which memory load was varied for both features. We found that the spatial information memory load does not affect the ability to store information about serial order and vice versa. Furthermore, movement response latencies indicated that retrieval of information about both features proceeds simultaneously. These results strongly favor independent, parallel working memory systems for processing space and order information in the motor system.

The effects of increasing memory load on the directional accuracy of pointing movements to remembered targets.

The directional accuracy of pointing arm movements to remembered targets in conditions of increasing memory load was investigated using a modified version of the Sternberg's context-recall memory-scanning task. Series of 2, 3 or 4 targets (chosen randomly from a set of 16 targets around a central starting point in 2D space) were presented sequentially, followed by a cue target randomly selected from the series excluding the last one. The subject had to move to the location of the next target in the series. Correct movements were those that ended closer to the instructed target than any other target in the series while all other movements were considered as serial order errors. Increasing memory load resulted in a large decrease in the directional accuracy or equivalently in the directional information transmitted by the motor system. The constant directional error varied with target direction in a systematic fashion reproducing previous results and suggesting the same systematic distortion of the representation of direction in different memory delay tasks. The constant directional error was not altered by increasing memory load, contradicting our hypothesis that it might reflect a cognitive strategy for better remembering spatial locations in conditions of increasing uncertainty. Increasing memory load resulted in a linear increase of mean response time and variable directional error and a non-linear increase in the percentage of serial order errors. Also the percentage of serial order errors for the last presented target in the series was smaller (recency effect). The difference between serial order and directional spatial accuracy is supported by neurophysiological and functional anatomical evidence of working memory subsystems in the prefrontal cortex.