Dynamic computational phenotyping of human cognition.

Computational phenotyping has emerged as a powerful tool for characterizing individual variability across a variety of cognitive domains. An individual's computational phenotype is defined as a set of mechanistically interpretable parameters obtained from fitting computational models to behavioural data. However, the interpretation of these parameters hinges critically on their psychometric properties, which are rarely studied. To identify the sources governing the temporal variability of the computational phenotype, we carried out a 12-week longitudinal study using a battery of seven tasks that measure aspects of human learning, memory, perception and decision making. To examine the influence of state effects, each week, participants provided reports tracking their mood, habits and daily activities. We developed a dynamic computational phenotyping framework, which allowed us to tease apart the time-varying effects of practice and internal states such as affective valence and arousal. Our results show that many phenotype dimensions covary with practice and affective factors, indicating that what appears to be unreliability may reflect previously unmeasured structure. These results support a fundamentally dynamic understanding of cognitive variability within an individual.

Dissociating distinct cortical networks associated with subregions of the human medial temporal lobe using precision neuroimaging.

Tract-tracing studies in primates indicate that different subregions of the medial temporal lobe (MTL) are connected with multiple brain regions. However, no clear framework defining the distributed anatomy associated with the human MTL exists. This gap in knowledge originates in notoriously low MRI data quality in the anterior human MTL and in group-level blurring of idiosyncratic anatomy between adjacent brain regions, such as entorhinal and perirhinal cortices, and parahippocampal areas TH/TF. Using MRI, we intensively scanned four human individuals and collected whole-brain data with unprecedented MTL signal quality. Following detailed exploration of cortical networks associated with MTL subregions within each individual, we discovered three biologically meaningful networks associated with the entorhinal cortex, perirhinal cortex, and parahippocampal area TH, respectively. Our findings define the anatomical constraints within which human mnemonic functions must operate and are insightful for examining the evolutionary trajectory of the MTL connectivity across species.

Motor learning in hemi-Parkinson using VR-manipulated sensory feedback.

AIMS: Modalities for rehabilitation of the neurologically affected upper-limb (UL) are generally of limited benefit. The majority of patients seriously affected by UL paresis remain with severe motor disability, despite all rehabilitation efforts. Consequently, extensive clinical research is dedicated to develop novel strategies aimed to improve the functional outcome of the affected UL. We have developed a novel virtual-reality training tool that exploits the voluntary control of one hand and provides real-time movement-based manipulated sensory feedback as if the other hand is the one that moves. The aim of this study was to expand our previous results, obtained in healthy subjects, to examine the utility of this training setup in the context of neuro-rehabilitation. METHODS: We tested the training setup in patient LA, a young man with significant unilateral UL dysfunction stemming from hemi-parkinsonism. LA underwent daily intervention in which he intensively trained the non-affected upper limb, while receiving online sensory feedback that created an illusory perception of control over the affected limb. Neural changes were assessed using functional magnetic resonance imaging (fMRI) scans before and after training. RESULTS: Training-induced behavioral gains were accompanied by enhanced activation in the pre-frontal cortex and a widespread increase in resting-state functional connectivity. DISCUSSION: Our combination of cutting edge technologies, insights gained from basic motor neuroscience in healthy subjects and well-known clinical treatments, hold promise for the pursuit of finding novel and more efficient rehabilitation schemes for patients suffering from hemiplegia.Implications for rehabilitationAssistive devices used in hospitals to support patients with hemiparesis require expensive equipment and trained personnel - constraining the amount of training that a given patient can receive. The setup we describe is simple and can be easily used at home with the assistance of an untrained caregiver/family member. Once installed at the patient's home, the setup is lightweight, mobile, and can be used with minimal maintenance . Building on advances in machine learning, our software can be adapted to personal use at homes. Our findings can be translated into practice with relatively few adjustments, and our experimental design may be used as an important adjuvant to standard clinical care for upper limb hemiparesis.

Action-locked Neural Responses in Auditory Cortex to Self-generated Sounds.

Sensory perception is a product of interactions between the internal state of an organism and the physical attributes of a stimulus. It has been shown across the animal kingdom that perception and sensory-evoked physiological responses are modulated depending on whether or not the stimulus is the consequence of voluntary actions. These phenomena are often attributed to motor signals sent to relevant sensory regions that convey information about upcoming sensory consequences. However, the neurophysiological signature of action-locked modulations in sensory cortex, and their relationship with perception, is still unclear. In the current study, we recorded neurophysiological (using Magnetoencephalography) and behavioral responses from 16 healthy subjects performing an auditory detection task of faint tones. Tones were either generated by subjects' voluntary button presses or occurred predictably following a visual cue. By introducing a constant temporal delay between button press/cue and tone delivery, and applying source-level analysis, we decoupled action-locked and auditory-locked activity in auditory cortex. We show action-locked evoked-responses in auditory cortex following sound-triggering actions and preceding sound onset. Such evoked-responses were not found for button-presses that were not coupled with sounds, or sounds delivered following a predictive visual cue. Our results provide evidence for efferent signals in human auditory cortex that are locked to voluntary actions coupled with future auditory consequences.

Voluntary Actions Modulate Perception and Neural Representation of Action-Consequences in a Hand-Dependent Manner.

Evoked neural activity in sensory regions and perception of sensory stimuli are modulated when the stimuli are the consequence of voluntary movement, as opposed to an external source. It has been suggested that such modulations are due to motor commands that are sent to relevant sensory regions during voluntary movement. However, given the anatomical-functional laterality bias of the motor system, it is plausible that the pattern of such behavioral and neural modulations will also exhibit a similar bias, depending on the effector triggering the stimulus (e.g., right/left hand). Here, we examined this issue in the visual domain using behavioral and neural measures (fMRI). Healthy participants judged the relative brightness of identical visual stimuli that were either self-triggered (using right/left hand button presses), or triggered by the computer. Stimuli were presented either in the right or left visual field. Despite identical physical properties of the visual consequences, we found stronger perceptual modulations when the triggering hand was ipsi- (rather than contra-) lateral to the stimulated visual field. Additionally, fMRI responses in visual cortices differentiated between stimuli triggered by right/left hand. Our findings support a model in which voluntary actions induce sensory modulations that follow the anatomical-functional bias of the motor system.

Motor output, neural states and auditory perception.

Behavior is a complex product of interactions between sensory influx arising from the environment and the neural state of the organism. Therefore, identical sensory input can elicit different behavioral responses. Research in recent years has demonstrated that perception is modulated when an organism is engaged in active behavior - suggesting that neural activity in motor pathways is one factor governing the neural state of networks engaged in sensory processing. In the current manuscript, we focus on the auditory modality and propose a mechanism by which activity in motor cortex changes the neural state in auditory cortex through global inhibition. In turn, such global inhibition reduces auditory net population activity, sharpens auditory frequency tuning curves, shifts the auditory oscillatory state and increases the signal-to-noise ratio of auditory evoked neural activity. These changes can result in either attenuated or enhanced behavioral responses depending on the environmental context. We base our model on animal and human literature and suggest that these motor-induced shifts in sensory states may explain reported phenomena and apparent discrepancies in the literature of motor-sensory interactions, such as sensory attenuation or sensory enhancement.

Predicted sensory consequences of voluntary actions modulate amplitude of preceding readiness potentials.

Self-generated, voluntary actions, are preceded by a slow negativity in the scalp electroencephalography (EEG) signal recorded from frontal regions (termed 'readiness potential'; RP). This signal, and its lateralized subcomponent (LRP), is mainly regarded as preparatory motor activity associated with the forthcoming voluntary motor act. However, it is not clear whether this neural signature is associated with preparatory motor activity, expectation of its associated sensory consequences, or both. Here we recorded EEG data from 14 healthy subjects while they performed self-paced button presses with their right index and middle fingers. Button-presses with one finger triggered a sound (motor+sound condition), while button-presses with the other finger did not (motor-only condition). Additionally, subjects listened to externally-generated sounds delivered in expected timings (sound-only condition). We found that the RP amplitude (locked to time of button press) was significantly more negative in the motor+sound compared with motor-only conditions. Importantly, no signal negativity was observed prior to expected sound delivery in the sound-only condition. Thus, the differences in RP amplitude between motor+sound and motor-only conditions are beyond differences in mere expectation of a forthcoming auditory sound. Our results suggest that information regarding expected auditory consequences is represented in the RP preceding voluntary action execution.

Suppression of EEG mu rhythm during action observation corresponds with subsequent changes in behavior.

Movement is intrinsically linked to perception such that observing an action induces in the observer behavioral changes during execution of similar actions. Electroencephalogram (EEG) studies have revealed that at the group level, action observation suppresses oscillatory power in mu (8-12 Hz) and beta (15-25 Hz) bands over the sensorimotor cortex - a phenomenon associated with increased excitability of cortical neurons. However, it is unclear whether differences in suppression level across individuals is linked with individual differences in subsequent behavioral changes. Here 32 subjects performed self-paced finger tapping with their right hand before and after observation of a video displaying finger-tapping at either 2 or 4 Hz. Behaviorally, subjects' rate of self-pace tapping increased following observation, with higher increases following 4 Hz observation. The level of EEG power suppression in the low frequency range (low mu; 8-10 Hz) during observation corresponded to subsequent behavioral changes in tapping rate across individuals. Our results demonstrate that observing actions implicitly shifts subsequent execution rates, and that individual differences in the level of this implicit shift can be explained by activity in the sensorimotor cortex during observation.

Perceived loudness of self-generated sounds is differentially modified by expected sound intensity.

Performing actions with sensory consequences modifies physiological and behavioral responses relative to otherwise identical sensory input perceived in a passive manner. It is assumed that such modifications occur through an efference copy sent from motor cortex to sensory regions during performance of voluntary actions. In the auditory domain most behavioral studies report attenuated perceived loudness of self-generated auditory action-consequences. However, several recent behavioral and physiological studies report enhanced responses to such consequences. Here we manipulated the intensity of self-generated and externally-generated sounds and examined the type of perceptual modification (enhancement vs. attenuation) reported by healthy human subjects. We found that when the intensity of self-generated sounds was low, perceived loudness is enhanced. Conversely, when the intensity of self-generated sounds was high, perceived loudness is attenuated. These results might reconcile some of the apparent discrepancies in the reported literature and suggest that efference copies can adapt perception according to the differential sensory context of voluntary actions.

Enhanced auditory evoked activity to self-generated sounds is mediated by primary and supplementary motor cortices.

Accumulating evidence demonstrates that responses in auditory cortex to auditory consequences of self-generated actions are modified relative to the responses evoked by identical sounds generated by an external source. Such modifications have been suggested to occur through a corollary discharge sent from the motor system, although the exact neuroanatomical origin is unknown. Furthermore, since tactile input has also been shown to modify responses in auditory cortex, it is not even clear whether the source of such modifications is motor output or somatosensory feedback. We recorded functional magnetic resonance imaging (fMRI) data from healthy human subjects (n = 11) while manipulating the rate at which they performed sound-producing actions with their right hand. In addition, we manipulated the amount of tactile feedback to examine the relative roles of motor and somatosensory cortices in modifying evoked activity in auditory cortex (superior temporal gyrus). We found an enhanced fMRI signal in left auditory cortex during perception of self-generated sounds relative to passive listening to identical sounds. Moreover, the signal difference between active and passive conditions in left auditory cortex covaried with the rate of sound-producing actions and was invariant to the amount of tactile feedback. Together with functional connectivity analysis, our results suggest motor output from supplementary motor area and left primary motor cortex as the source of signal modification in auditory cortex during perception of self-generated sounds. Motor signals from these regions could represent a predictive signal of the expected auditory consequences of the performed action.

Lateralized enhancement of auditory cortex activity and increased sensitivity to self-generated sounds.

Performing actions with auditory consequences modulates the response in auditory cortex to otherwise identical stimuli passively heard. Such modulation has been suggested to occur through a corollary discharge sent from the motor cortex during voluntary actions. However, the relationship between the effector used to generate the sound, type of modulation and changes in perceptual sensitivity are unclear. Here we use functional magnetic resonance imaging on healthy subjects and demonstrate bilateral enhancement in the auditory cortex to self-generated versus externally generated sounds. Furthermore, we find that this enhancement is stronger when the sound-producing hand is contralateral to the auditory cortex. At the behavioural level, binaural hearing thresholds are lower for self-generated sounds and monaural thresholds are lower for sounds triggered by the hand ipsilateral to the stimulated ear. Together with functional connectivity analysis, our results suggest that a corollary discharge sent from active motor cortex enhances activity in the auditory cortex and increases perceptual sensitivity in a lateralized manner.

Implications of number-space synesthesia on the automaticity of numerical processing.

Number-space synesthetes visualize numbers in specific spatial configurations. Their spatial-numerical perceptions are assumed to be automatic in nature and have been found to affect performance in various numerical tasks. The current study tested whether synesthetic number-space associations can modulate the well-established Size Congruency Effect (SiCE), which is considered to be an indication for the automaticity of numerical processing. Two groups, number-space synesthetes and matched controls, were tested on a numerical Stroop task (Henik and Tzelgov, 1982). In separate blocks, participants were presented with two digits and asked to make comparative judgments regarding either numerical values (numerical comparison) or physical size (physical comparison). Both dimensions were manipulated orthogonally, creating three congruency levels: congruent (e.g., 2 7), incongruent (e.g., 2 7) and neutral (e.g., 2 2 and 2 7 for physical and numerical blocks, respectively). For the numerical block, both synesthetes and controls showed the classic SiCE, indicating similar automatic processing of physical magnitude. However, in the physical block, synesthetes showed a lack of automatic numerical magnitude processing when the numbers to be compared were presented incompatibly with their relative position on the synesthetic number-form. This finding strongly suggests that synesthetes' number-space perceptions affect their ability to automatically process the semantic meaning of numerals. The involvement of space in automatic magnitude processing for number-space synesthetes and non-synesthetes is discussed.