Dynamical and individualised approach of transcranial ultrasound neuromodulation effects in non-human primates

Low-frequency transcranial ultrasound stimulation (TUS) allows to alter brain functioning with a high spatial resolution and to reach deep targets. However, the time-course of TUS effects remains largely unknown. We applied TUS on three brain targets for three different monkeys: the anterior medial prefrontal cortex, the supplementary motor area and the perigenual anterior cingulate cortex. For each, one resting-state fMRI was acquired between 30 and 150 min after TUS as well as one without stimulation (control). We captured seed-based brain connectivity changes dynamically and on an individual basis. We also assessed between individuals and between targets homogeneity and brain features that predicted TUS changes. We found that TUS prompts heterogenous functional connectivity alterations yet retain certain consistent changes; we identified 6 time-courses of changes including transient and long duration alterations; with a notable degree of accuracy we found that brain alterations could partially be predicted. Altogether, our results highlight that TUS induces heterogeneous functional connectivity alterations. On a more technical point, we also emphasize the need to consider brain changes over-time rather than just observed during a snapshot; to consider inter-individual variability since changes could be highly different from one individual to another

Tourette syndrome research highlights from 2021

We summarize selected research reports from 2021 relevant to Tourette syndrome that the authors consider most important or interesting. The authors welcome article suggestions and thoughtful feedback from readers

The sooner the better: clinical and neural correlates of impulsive choice in Tourette disorder.

Reward sensitivity has been suggested as one of the central pathophysiological mechanisms in Tourette disorder. However, the subjective valuation of a reward by introduction of delay has received little attention in Tourette disorder, even though it has been suggested as a trans-diagnostic feature of numerous neuropsychiatric disorders. We aimed to assess delay discounting in Tourette disorder and to identify its brain functional correlates. We evaluated delayed discounting and its brain functional correlates in a large group of 54 Tourette disorder patients and 31 healthy controls using a data-driven approach. We identified a subgroup of 29 patients with steeper reward discounting, characterised by a higher burden of impulse-control disorders and a higher level of general impulsivity compared to patients with normal behavioural performance or to controls. Reward discounting was underpinned by resting-state activity of a network comprising the orbito-frontal, cingulate, pre-supplementary motor area, temporal and insular cortices, as well as ventral striatum and hippocampus. Within this network, (i) lower connectivity of pre-supplementary motor area with ventral striatum predicted a higher impulsivity and a steeper reward discounting and (ii) a greater connectivity of pre-supplementary motor area with anterior insular cortex predicted steeper reward discounting and more severe tics. Overall, our results highlight the heterogeneity of the delayed reward processing in Tourette disorder, with steeper reward discounting being a marker of burden in impulsivity and impulse control disorders, and the pre-supplementary motor area being a hub region for the delay discounting, impulsivity and tic severity

Impulsive prepotent actions and tics in Tourette disorder underpinned by a common neural network.

Tourette disorder (TD), which is characterized by motor and vocal tics, is not in general considered as a product of impulsivity, despite a frequent association with attention deficit hyperactivity disorder and impulse control disorders. It is unclear which type of impulsivity, if any, is intrinsically related to TD and specifically to the severity of tics. The waiting type of motor impulsivity, defined as the difficulty to withhold a specific action, shares some common features with tics. In a large group of adult TD patients compared to healthy controls, we assessed waiting motor impulsivity using a behavioral task, as well as structural and functional underpinnings of waiting impulsivity and tics using multi-modal neuroimaging protocol. We found that unmedicated TD patients showed increased waiting impulsivity compared to controls, which was independent of comorbid conditions, but correlated with the severity of tics. Tic severity did not account directly for waiting impulsivity, but this effect was mediated by connectivity between the right orbito-frontal cortex with caudate nucleus bilaterally. Waiting impulsivity in unmedicated patients with TD also correlated with a higher gray matter signal in deep limbic structures, as well as connectivity with cortical and with cerebellar regions on a functional level. Neither behavioral performance nor structural or functional correlates were related to a psychometric measure of impulsivity or impulsive behaviors in general. Overall, the results suggest that waiting impulsivity in TD was related to tic severity, to functional connectivity of orbito-frontal cortex with caudate nucleus and to structural changes within limbic areas

Traumatic brain injury in England and Wales: prospective audit of epidemiology, complications and standardised mortality.

OBJECTIVES: To provide a comprehensive assessment of the management of traumatic brain injury (TBI) relating to epidemiology, complications and standardised mortality across specialist units. DESIGN: The Trauma Audit and Research Network collects data prospectively on patients suffering trauma across England and Wales. We analysed all data collected on patients with TBI between April 2014 and June 2015. SETTING: Data were collected on patients presenting to emergency departments across 187 hospitals including 26 with specialist neurosurgical services, incorporating factors previously identified in the Ps14 multivariate logistic regression (Ps14n) model multivariate TBI outcome prediction model. The frequency and timing of secondary transfer to neurosurgical centres was assessed. RESULTS: We identified 15 820 patients with TBI presenting to neurosurgical centres directly (6258), transferred from a district hospital to a neurosurgical centre (3682) and remaining in a district general hospital (5880). The commonest mechanisms of injury were falls in the elderly and road traffic collisions in the young, which were more likely to present in coma. In severe TBI (Glasgow Coma Score (GCS) ≤8), the median time from admission to imaging with CT scan is 0.5 hours. Median time to craniotomy from admission is 2.6 hours and median time to intracranial pressure monitoring is 3 hours. The most frequently documented complication of severe TBI is bronchopneumonia in 5% of patients. Risk-adjusted W scores derived from the Ps14n model indicate that no neurosurgical unit fell outside the 3 SD limits on a funnel plot. CONCLUSIONS: We provide the first comprehensive report of the management of TBI in England and Wales, including data from all neurosurgical units. These data provide transparency and suggests equity of access to high-quality TBI management provided in England and Wales.AH is supported by the University of Cambridge, UK and Medical Research Council/Royal College of Surgeons of England Clinical Research Training Fellowship (Grant no. G0802251). P.J.H. is supported by National Institute for Health Research Professorship, Academy of Medical Sciences/Health Foundation Senior Surgical Scientist Fellowship and the National Institute for Health Research Biomedical Research Centre, Cambridge.This is the final version of the article. It first appeared from the BMJ Publishing Group. via https://doi.org/10.1136/bmjopen-2016- 01219

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements