A Bayesian account of the sensory-motor interactions underlying symptoms in Tourette syndrome

Tourette syndrome is a hyperkinetic movement disorder. Characteristic features include tics, recurrent movements that are experienced as compulsive and “unwilled”; uncomfortable premonitory sensations that resolve through tic release; and often, the ability to suppress tics temporarily. We demonstrate how these symptoms and features can be understood in terms of aberrant predictive (Bayesian) processing in hierarchical neural systems, explaining specifically: why tics arise, their “unvoluntary” nature, how premonitory sensations emerge, and why tic suppression works—sometimes. In our model, premonitory sensations and tics are generated through over-precise priors for sensation and action within somatomotor regions of the striatum. Abnormally high precision of priors arises through the dysfunctional synaptic integration of cortical inputs. These priors for sensation and action are projected into primary sensory and motor areas, triggering premonitory sensations and tics, which in turn elicit prediction errors for unexpected feelings and movements. We propose experimental paradigms to validate this Bayesian account of tics. Our model integrates behavioural, neuroimaging, and computational approaches to provide mechanistic insight into the pathophysiological basis of Tourette syndrome

The prefrontal cortex achieves inhibitory control by facilitating subcortical motor pathway connectivity

Communication between the prefrontal cortex and subcortical nuclei underpins the control and inhibition of behavior. However, the interactions in such pathways remain controversial. Using a stop-signal response inhibition task and functional imaging with analysis of effective connectivity, we show that the lateral prefrontal cortex influences the strength of communication between regions in the frontostriatal motor system. We compared 20 generative models that represented alternative interactions between the inferior frontal gyrus, presupplementary motor area (preSMA), subthalamic nucleus (STN), and primary motor cortex during response inhibition. Bayesian model selection revealed that during successful response inhibition, the inferior frontal gyrus modulates an excitatory influence of the preSMA on the STN, thereby amplifying the downstream polysynaptic inhibition from the STN to the motor cortex. Critically, the strength of the interaction between preSMA and STN, and the degree of modulation by the inferior frontal gyrus, predicted individual differences in participants’ stopping performance (stop-signal reaction time). We then used diffusion-weighted imaging with tractography to assess white matter structure in the pathways connecting these three regions. The mean diffusivity in tracts between preSMA and the STN, and between the inferior frontal gyrus and STN, also predicted individual differences in stopping efficiency. Finally, we found that white matter structure in the tract between preSMA and STN correlated with effective connectivity of the same pathway, providing important cross-modal validation of the effective connectivity measures. Together, the results demonstrate the network dynamics and modulatory role of the prefrontal cortex that underpin individual differences in inhibitory control

Impairment of perceptual metacognitive accuracy and reduced prefrontal grey matter volume in first-episode psychosis

Introduction: Metacognition, or “thinking about thinking”, is a higher-order thought process that allows for the evaluation of perceptual processes for accuracy. Metacognitive accuracy is associated with the grey matter volume (GMV) in the prefrontal cortex (PFC), an area also impacted in schizophrenia. The present study set out to investigate whether deficits in metacognitive accuracy are present in the early stages of psychosis. Methods: Metacognitive accuracy in first-episode psychosis (FEP) was assessed on a perceptual decision making task and their performance compared to matched healthy control participants (N = 18). A novel signal detection theory approach was used to model metacognitive sensitivity independently from objective perceptual performance. A voxel-based morphometry investigation was also conducted on GMV. Results: We found that the FEP group demonstrated significantly worse metacognitive accuracy compared to controls (p = .039). Importantly, GMV deficits were also observed in the superior frontal gyrus. The findings suggest a specific deficit in this processing domain to exist at first episode; however, no relationship was found between GMV and metacognitive accuracy. Conclusions: Our findings support the notion that an inability to accurately scrutinise perception may underpin functional deficits observed in later schizophrenia; however, the exact neural basis of metacognitive deficits in FEP remains elusive

Network abnormalities in generalized anxiety pervade beyond the amygdala-prefrontal cortex circuit: insights from graph theory

Generalized anxiety (GAD) has excessive anxiety and uncontrollable worry as core symptoms. Abnormal cerebral functioning underpins the expression and perhaps pathogenesis of GAD: Studies implicate impaired communication between the amygdala and the pre-frontal cortex (PFC). Our aim was to longitudinally investigate whether such network abnormalities are spatially restricted to this circuit or if the integrity of functional brain networks is globally disrupted in GAD. We acquired resting-state functional magnetic resonance imaging data from 16 GAD patients and 16 matched controls at baseline and after 1 year. Using network modelling and graph-theory, whole-brain connectivity was characterized from local and global perspectives. Overall lower global efficiency, indicating sub-optimal brain-wide organization and integration, was present in patients with GAD compared to controls. The amygdala and midline cortices showed higher betweenness centrality, reflecting functional dominance of these brain structures. Third, lower betweenness centrality and lower degree emerged for PFC, suggesting weakened inhibitory control. Overall, network organization showed impairments consistent with neurobiological models of GAD (involving amygdala, PFC, and cingulate cortex) and further pointed to an involvement of temporal regions. Such impairments tended to progress over time and predict anxiety symptoms. A graph-analytic approach represents a powerful approach to deepen our understanding of GAD

Climate crisis and ecological emergency: why they concern (neuro)scientists, and what we can do

Our planet is experiencing severe and accelerating climate and ecological breakdown caused by human activity. As professional scientists, we are better placed than most to understand the data that evidence this fact. However, like most other people, we ignore this inconvenient truth and lead our daily lives, at home and at work, as if these facts weren’t true. In particular, we overlook that our own neuroscientific research practices, from our laboratory experiments to our often global travel, help drive climate change and ecosystem damage. We also hold privileged positions of authority in our societies but rarely speak out. Here, we argue that to help society create a survivable future, we neuroscientists can and must play our part. In April 2021, we delivered a symposium at the British Neuroscience Association meeting outlining what we think neuroscientists can and should do to help stop climate breakdown. Building on our talks (Box 1), we here outline what the climate and ecological emergencies mean for us as neuroscientists. We highlight the psychological mechanisms that block us from taking action, and then outline what practical steps we can take to overcome these blocks and work towards sustainability. In particular, we review environmental issues in neuroscience research, scientific computing, and conferences. We also highlight the key advocacy roles we can all play in our institutions and in society more broadly. The need for sustainable change has never been more urgent, and we call on all (neuro)scientists to act with the utmost urgency

Impact of cardiac interoception cues and confidence on voluntary decisions to make or withhold action in an intentional inhibition task

Interoceptive signals concerning the internal physiological state of the body influence motivational feelings and action decisions. Cardiovascular arousal may facilitate inhibition to mitigate risks of impulsive actions. Baroreceptor discharge at ventricular systole underpins afferent signalling of cardiovascular arousal. In a modified Go/NoGo task, decisions to make or withhold actions on ‘Choose’ trials were not influenced by cardiac phase, nor individual differences in heart rate variability. However, cardiac interoceptive awareness and insight predicted how frequently participants chose to act, and their speed of action: Participants with better awareness and insight tended to withhold actions and respond slower, while those with poorer awareness and insight tended to execute actions and respond faster. Moreover, self-reported trait urgency correlated negatively with intentional inhibition rates. These findings suggest that lower insight into bodily signals is linked to urges to move the body, putatively by engendering noisier sensory input into motor decision processes eliciting reactive behaviour

Regular fat and reduced fat dairy products show similar associations with markers of adolescent cardiometabolic health

Reduced fat dairy products are generally recommended for adults and children over the age of two years. However, emerging evidence suggests that dairy fat may not have detrimental health effects. We aimed to investigate prospective associations between consumption of regular versus reduced fat dairy products and cardiometabolic risk factors from early to late adolescence. In the West Australian Raine Study, dairy intake was assessed using semi-quantitative food frequency questionnaires in 860 adolescents at 14 and 17-year follow-ups; 582 of these also had blood biochemistry at both points. Using generalized estimating equations, we examined associations with cardiometabolic risk factors. Models incorporated reduced fat and regular fat dairy together (in serves/day) and were adjusted for a range of factors including overall dietary pattern. In boys, there was a mean reduction in diastolic blood pressure of 0.66 mmHg (95% CI 0.23–1.09) per serve of reduced fat dairy and an independent, additional reduction of 0.47 mmHg (95% CI 0.04–0.90) per serve of regular fat dairy. Each additional serve of reduced fat dairy was associated with a 2% reduction in HDL-cholesterol (95% CI 0.97–0.995) and a 2% increase in total: HDL-cholesterol ratio (95% CI 1.002–1.03); these associations were not observed with regular fat products. In girls, there were no significant independent associations observed in fully adjusted models. Although regular fat dairy was associated with a slightly better cholesterol profile in boys, overall, intakes of both regular fat and reduced fat dairy products were associated with similar cardiometabolic associations in adolescents

Predicting beneficial effects of atomoxetine and citalopram on response inhibition in Parkinson's disease with clinical and neuroimaging measures.

Recent studies indicate that selective noradrenergic (atomoxetine) and serotonergic (citalopram) reuptake inhibitors may improve response inhibition in selected patients with Parkinson's disease, restoring behavioral performance and brain activity. We reassessed the behavioral efficacy of these drugs in a larger cohort and developed predictive models to identify patient responders. We used a double-blind randomized three-way crossover design to investigate stopping efficiency in 34 patients with idiopathic Parkinson's disease after 40 mg atomoxetine, 30 mg citalopram, or placebo. Diffusion-weighted and functional imaging measured microstructural properties and regional brain activations, respectively. We confirmed that Parkinson's disease impairs response inhibition. Overall, drug effects on response inhibition varied substantially across patients at both behavioral and brain activity levels. We therefore built binary classifiers with leave-one-out cross-validation (LOOCV) to predict patients' responses in terms of improved stopping efficiency. We identified two optimal models: (1) a "clinical" model that predicted the response of an individual patient with 77-79% accuracy for atomoxetine and citalopram, using clinically available information including age, cognitive status, and levodopa equivalent dose, and a simple diffusion-weighted imaging scan; and (2) a "mechanistic" model that explained the behavioral response with 85% accuracy for each drug, using drug-induced changes of brain activations in the striatum and presupplementary motor area from functional imaging. These data support growing evidence for the role of noradrenaline and serotonin in inhibitory control. Although noradrenergic and serotonergic drugs have highly variable effects in patients with Parkinson's disease, the individual patient's response to each drug can be predicted using a pattern of clinical and neuroimaging features.The BCNI is supported by the Wellcome Trust and Medical Research Council. We are grateful to Dr Gordon Logan for advice on stop-signal reaction time estimation and to Dr Marta Correia for advice on diffusion-weighted imaging data analysis. Conflict of interest: Prof. Sahakian has received grants from Janssen/J&J, personal fees from Cambridge Cognition, personal fees from Lundbeck, and personal fees from Servier, outside the submitted work. Prof. Robbins has received personal fees and royalties from Cambridge Cognition, personal fees and grants from Eli Lilly Inc, personal fees and grants from Lundbeck, grants from GSK, personal fees from Teva Pharmaceuticals, personal fees from Shire Pharmaceuticals, grants from Medical Research Council, editorial honorarium from Springer Verlag Germany, and personal fees from Chempartners, outside the submitted work. Prof. Rowe has received grant funding from AZ-Medimmune unrelated to the current work. Dr Housden is an employee of Cambridge Cognition. Other authors reported no biomedical financial interests or potential conflict of interest.This is the final version of the article. It was first available from Wiley via http://dx.doi.org/10.1002/hbm.2308

Subjective embodiment during the rubber hand illusion predicts severity of premonitory sensations and tics in Tourette Syndrome

In Tourette Syndrome, the expression of tics and commonly preceding premonitory sensations is associated with perturbed subjective feelings of self-control and agency. We compared responses to the Rubber Hand Illusion in 23 adults with TS and 22 controls. Both TS and control participants reported equivalent subjective embodiment of the artificial hand: feelings of ownership, location, and agency were greater during synchronous visuo-tactile stimulation, compared to asynchronous. However, individuals with TS did not manifest greater proprioceptive drift, an objective marker of embodiment observed in controls. An 'embodiment prediction error' index of the difference between subjective embodiment and objective proprioceptive drift correlated with severity of premonitory sensations. Feelings of ownership also correlated with premonitory sensation severity, and feelings of agency with tic severity. These findings suggest that subjective bodily ownership, as measured by the rubber hand illusion, contributes to susceptibility to the premonitory sensations that may be a precipitating factor in tics