Gita Prabhu

Having a body versus moving your body: How agency structures body-ownership

We investigated how motor agency in the voluntary control of body movement influences body awareness. In the Rubber Hand Illusion (RHI), synchronous tactile stimulation of a rubber hand and the participants hand leads to a feeling of the rubber hand being incorporated in the participants own body. One quantifiable behavioural correlate of the illusion is an induced shift in the perceived location of the participants hand towards the rubber hand. Previous studies showed that the induced changes in body awareness are local and fragmented: the proprioceptive drift is largely restricted to the stimulated finger. In the present study, we investigated whether active and passive movements, rather than tactile stimulation, would lead to similarly fragmented body awareness. Participants watched a projected image of their hand under three conditions: active finger movement, passive finger movement, and tactile stimulation. Visual feedback was either synchronous or asynchronous with respect to stimulation of the hand. A significant overall RHI, defined as greater drifts following synchronous than asynchronous stimulation, was found in all cases. However, the distribution of the RHI across stimulated and non-stimulated fingers depended on the kind of stimulation. Localised proprioceptive drifts, specific to the stimulated finger, were found for tactile and passive stimulation. Conversely, during active movement of a single digit, the proprioceptive drifts were not localised to that digit, but were spread across the whole hand. Whereas a purely proprioceptive sense of body-ownership is local and fragmented, the motor sense of agency integrates distinct body-parts into a coherent, unified awareness of the body.

Adolescence is associated with genomically patterned consolidation of the hubs of the human brain connectome

Significance Adolescence is a period of human brain growth and high incidence of mental health disorders. Here, we show consistently in two MRI cohorts that human brain changes in adolescence were concentrated on the more densely connected hubs of the connectome (i.e., association cortical regions that mediated efficient connectivity throughout the human brain structural network). Hubs were less myelinated at 14 y but had faster rates of myelination and cortical shrinkage in the 14- to 24-y period. This topologically focused process of cortical consolidation was associated with expression of genes enriched for normal synaptic and myelin-related processes and risk of schizophrenia. Consolidation of anatomical network hubs could be important for normal and clinically disordered adolescent brain development. How does human brain structure mature during adolescence? We used MRI to measure cortical thickness and intracortical myelination in 297 population volunteers aged 14–24 y old. We found and replicated that association cortical areas were thicker and less myelinated than primary cortical areas at 14 y. However, association cortex had faster rates of shrinkage and myelination over the course of adolescence. Age-related increases in cortical myelination were maximized approximately at the internal layer of projection neurons. Adolescent cortical myelination and shrinkage were coupled and specifically associated with a dorsoventrally patterned gene expression profile enriched for synaptic, oligodendroglial- and schizophrenia-related genes. Topologically efficient and biologically expensive hubs of the brain anatomical network had greater rates of shrinkage/myelination and were associated with overexpression of the same transcriptional profile as cortical consolidation. We conclude that normative human brain maturation involves a genetically patterned process of consolidating anatomical network hubs. We argue that developmental variation of this consolidation process may be relevant both to normal cognitive and behavioral changes and the high incidence of schizophrenia during human brain adolescence.

Excitability of human motor cortex inputs prior to grasp

Transcranial magnetic stimulation (TMS) was used to investigate corticospinal excitability during the preparation period preceding visually guided self‐paced grasping. Previously we have shown that while subjects prepare to grasp a visible object, paired‐pulse TMS at a specific interval facilitates motor‐evoked potentials (MEPs) in hand muscles in a manner that varies with the role of the muscle in shaping the hand for the upcoming grasp. This anticipatory modulation may reflect transmission of inputs to human primary motor cortex (M1) for visuomotor guidance of hand shape. Conversely, single‐pulse TMS is known to suppress MEPs during movement preparation. Here we investigate the time course of single‐ and paired‐pulse MEP modulation. TMS was delivered over M1, at different time intervals after visual presentation of either a handle or a disc to healthy subjects. Participants were instructed to view the object, and later to grasp it when given a cue. During grasp there was a specific pattern of hand muscle activity according to the object grasped. MEPs were evoked in these muscles by TMS delivered prior to grasp. Paired‐pulse MEPs were facilitated, whilst single‐pulse MEPs were suppressed. The pattern of facilitation matched the object‐specific pattern of muscle activity for TMS pulses delivered 150 ms or more after object presentation. However, this effect was not present when TMS was delivered immediately after object presentation, or if the delivery of TMS was given separately from the cue to perform the grasp action. These results suggest that object‐related information for preparation of appropriate hand shapes reaches M1 only immediately preceding execution of the grasp.

Ventral Premotor-Motor Cortex Interactions in the Macaque Monkey during Grasp: Response of Single Neurons to Intracortical Microstimulation

Recent stimulation studies in monkeys and humans have shown strong interactions between ventral premotor cortex (area F5) and the hand area of primary motor cortex (M1). These short-latency interactions usually involve facilitation from F5 of M1 outputs to hand muscles, although suppression has also been reported. This study, performed in three awake macaque monkeys, sought evidence that these interactions could be mediated by short-latency excitatory and inhibitory responses of single M1 neurons active during grasping tasks. We recorded responses of these M1 neurons to single low-threshold (≤40 μA) intracortical microstimuli delivered to F5 sites at which grasp-related neurons were recorded. In 29 sessions, we tested 232 M1 neurons with stimuli delivered to between one and four sites in F5. Of the 415 responses recorded, 142 (34%) showed significant effects. The most common type of response was pure excitation (53% of responses), with short latency (1.8–3.0 ms) and brief duration (∼1 ms); purely inhibitory responses had slightly longer latencies (2–5 ms) and were of small amplitude and longer duration (5–7 ms). They accounted for 13% of responses, whereas mixed excitation then inhibition was seen in 34%. Remarkably, a rather similar set of findings applied to 280 responses of 138 F5 neurons to M1 stimulation; 109 (34%) responses showed significant effects. Thus, with low-intensity stimuli, the dominant interaction between these two cortical areas is one of short-latency, brief excitation, most likely mediated by reciprocal F5–M1 connections. Some neurons were tested with stimuli at both 20 and 40 μA; inhibition tended to dominate at the higher intensity.

On-line control of grasping actions: object-specific motor facilitation requires sustained visual input.

Dorsal stream visual processing is generally considered to underlie visually driven action, but when subjects grasp an object from memory, as visual information is not available, ventral stream characteristics emerge. In this study we use paired-pulse transcranial magnetic stimulation (TMS) to investigate the importance of the current visual input during visuomotor grasp. Previously, the amplitude of the paired-pulse motor evoked potentials (MEPs) in hand muscles before movement onset have been shown to predict the subsequent pattern of muscle activity during grasp. Specific facilitation of paired-pulse MEPs may reflect premotor–motor (PMC–M1) cortex connectivity. Here we investigate the paired-pulse MEPs evoked under memory-cued and visually driven conditions before grasping one of two possible target objects (a handle or a disc). All trials began with a delay period of 1200 ms. Then, a TMS pulse served as the cue to reach, grasp and hold the target object for 0.5 s. Total trial length was 5 s. Both objects were continually visible in both conditions, but the way in which the target object was designated differed between conditions. In the memory-cued condition, the target object was illuminated for the first 200 ms of the trial only. In the visually driven condition, the target object was illuminated throughout the 5 s trial. Thus, the conditions differed in whether or not the object to be grasped was designated at the time of movement initiation. We found that the pattern of paired-pulse MEP facilitation matched the pattern of object-specific muscle activity only for the visually driven condition. The results suggest that PMC–M1 connectivity contributes to action selection only when immediate sensory information specifies which action to make.

Association of neural and emotional impacts of reward prediction errors with major depression

Importance Major depressive disorder (MDD) is associated with deficits in representing reward prediction errors (RPEs), which are the difference between experienced and predicted reward. Reward prediction errors underlie learning of values in reinforcement learning models, are represented by phasic dopamine release, and are known to affect momentary mood. Objective To combine functional neuroimaging, computational modeling, and smartphone-based large-scale data collection to test, in the absence of learning-related concerns, the hypothesis that depression attenuates the impact of RPEs. Design, Setting, and Participants Functional magnetic resonance imaging (fMRI) data were collected on 32 individuals with moderate MDD and 20 control participants who performed a probabilistic reward task. A risky decision task with repeated happiness ratings as a measure of momentary mood was also tested in the laboratory in 74 participants and with a smartphone-based platform in 1833 participants. The study was conducted from November 20, 2012, to February 17, 2015. Main Outcomes and Measures Blood oxygen level–dependent activity was measured in ventral striatum, a dopamine target area known to represent RPEs. Momentary mood was measured during risky decision making. Results Of the 52 fMRI participants (mean [SD] age, 34.0 [9.1] years), 30 (58%) were women and 32 had MDD. Of the 74 participants in the laboratory risky decision task (mean age, 34.2 [10.3] years), 44 (59%) were women and 54 had MDD. Of the smartphone group, 543 (30%) had a depression history and 1290 (70%) had no depression history; 918 (50%) were women, and 593 (32%) were younger than 30 years. Contrary to previous results in reinforcement learning tasks, individuals with moderate depression showed intact RPE signals in ventral striatum (z = 3.16; P = .002) that did not differ significantly from controls (z = 0.91; P = .36). Symptom severity correlated with baseline mood parameters in laboratory (&rgr; = −0.54; P < 1 × 10−6) and smartphone (&rgr; = −0.30; P < 1 × 10−39) data. However, participants with depression showed an intact association between RPEs and happiness in a computational model of momentary mood dynamics (z = 4.55; P < .001) that was not attenuated compared with controls (z = −0.42; P = .67). Conclusions and Relevance The neural and emotional impact of RPEs is intact in major depression. These results suggest that depression does not affect the expression of dopaminergic RPEs and that attenuated RPEs in previous reports may reflect downstream effects more closely related to aberrant behavior. The correlation between symptom severity and baseline mood parameters supports an association between depression and momentary mood fluctuations during cognitive tasks. These results demonstrate a potential for smartphones in large-scale computational phenotyping, which is a goal for computational psychiatry.

Cohort Profile: The NSPN 2400 Cohort: a developmental sample supporting the Wellcome Trust NeuroScience in Psychiatry Network

Cohort Profile: The NSPN 2400 Cohort: a developmental sample supporting the Wellcome Trust NeuroScience in Psychiatry Network Beatrix Kiddle, Becky Inkster, Gita Prabhu, Michael Moutoussis, Kirstie J Whitaker, the NSPN Consortium, Edward T Bullmore, Raymond J Dolan, Peter Fonagy, Ian M Goodyer, and Peter B Jones* Department of Psychiatry, University of Cambridge, United Kingdom, Wellcome Trust Centre for Neuroimaging, University College London, United Kingdom, Cambridgeshire and Peterborough National Health Service Foundation Trust, Cambridge, United Kingdom, Research Department of Clinical, Educational and Health Psychology, University College London, United Kingdom, Max Planck University College London Centre for Computational Psychiatry and Ageing Research, University College London, United Kingdom, Medical Research Council/Wellcome Trust Behavioural and Clinical Neuroscience Institute, University of Cambridge, United Kingdom, ImmunoPsychiatry, GlaxoSmithKline Research and Development, Stevenage, United Kingdom

Vigour in active avoidance

It would be maladaptive to learn about catastrophes by trial and error alone. Investment in planning and effort are necessary. Devoting too many resources to averting disaster, however, can impair quality of life, as in anxiety and paranoia. Here, we developed a novel task to explore how people adjust effort expenditure (vigor) so as to avoid negative consequences. Our novel paradigm is immersive, enabling us to measure vigor in the context of (simulated) disaster. We found that participants (N = 118) exerted effort to avoid disaster-associated states, adjusting their effort expenditure according to the baseline probability of catastrophe, in agreement with theoretical predictions. Furthermore, negative subjective emotional states were associated both with threat level and with increasing vigor in the face of disaster. We describe for the first time effort expenditure in the context of irreversible losses, with important implications for disorders marked by excessive avoidance.

Neural activity and fundamental learning, motivated by monetary loss and reward, are intact in mild to moderate major depressive disorder

Introduction Reduced motivation is an important symptom of major depression, thought to impair recovery by reducing opportunities for rewarding experiences. We characterized motivation for monetary outcomes in depressed outpatients (N = 39, 22 female) and controls (N = 22, 11 female) in terms of their effectiveness in seeking rewards and avoiding losses. We assessed motivational function during learning of associations between stimuli and actions, as well as when learning was complete. We compared the activity within neural circuits underpinning these behaviors between depressed patients and controls. Methods We used a Go/No-Go task that assessed subjects’ abilities in learning to emit or withhold actions to obtain monetary rewards or avoid losses. We derived motivation-relevant parameters of behavior (learning rate, Pavlovian bias, and motivational influence of gains and losses). After learning, participants performed the task during functional magnetic resonance imaging (fMRI). We compared neural activation during anticipation of action emission vs. action inhibition, and for actions performed to obtain rewards compared to actions that avoid losses. Results Depressed patients showed a similar Pavlovian bias to controls and were equivalent in terms of withholding action to gain rewards and emitting action to avoid losses, behaviors that conflict with well-described Pavlovian tendencies to approach rewards and avoid losses. Patients were not impaired in overall performance or learning and showed no abnormal neural responses, for example in bilateral midbrain or striatum. We conclude that basic mechanisms subserving motivated learning are thus intact in moderate depression. Implications Therapeutically, the intact mechanisms identified here suggest that learning-based interventions may be particularly effective in encouraging recovery. Etiologically, our results suggest that the severe motivational deficits clinically observed in depression are likely to have complex origins, possibly related to an impairment in the representation of future states necessary for long-term planning.

Data supporting NSPN publication "The NSPN 2400 Cohort: a developmental sample supporting the Wellcome Trust NeuroScience in Psychiatry Network"

Data supporting this publication can be found in the Kiddle_dataset.csv file. A brief description of the variables can be found in Kiddle_dataset_dictionary.txt.