Hypoactivation and Dysconnectivity of a Frontostriatal Circuit During Goal-Directed Planning as an Endophenotype for Obsessive-Compulsive Disorder

Background: The symptoms of Obsessive-Compulsive Disorder (OCD) have been postulated to result from impaired executive functioning and excessive habit formation at the expense of goal-directed control and have been objectively demonstrated using neuropsychological tests in such patients. This study tests whether there is functional hypoactivation as well as dysconnectivity of discrete frontostriatal pathways during goal-directed planning in OCD patients and in their unaffected first-degree relatives. Methods: Twenty-one comorbidity free OCD patients, 19 clinically asymptomatic first-degree relatives of these patients, and 20 control participants were tested on a functional magnetic resonance optimized version of the Tower of London task. Group differences in brain activation during goal-directed planning were measured together with associated frontostriatal functional connectivity. Results: OCD patients and their clinically asymptomatic relatives manifested hypoactivation of the right dorsolateral prefrontal cortex during goal-directed planning, coupled with reduced functional connectivity between this cortical region and the basal ganglia (putamen). Conclusions: Hypoactivation of cortical regions associated with goal-directed planning, and associated frontostriatal dysconnectivity, represent a candidate endophenotype for OCD. These findings accord with abnormalities in neural networks supporting the balance between goal-directed and habitual behavior, with implications for recent neuropsychological theories of OCD and the major neurobiological model for this disorder.This work was supported by a Wellcome Trust Senior Investigator Award (No. 104631/Z/14/Z) to TWR. Work was completed at the Behavioural and Clinical Neuroscience Institute, University of Cambridge, supported by a joint award from the Medical Research Council and Wellcome Trust (No. G00001354). MMV is supported by a Pinsent Darwin Scholarship in Mental Pathology and Angharad Dodds John Bursary in Mental Health and Neuropsychiatry. SRC’s involvement in this work was funded by a Wellcome Trust Clinical Fellowship (No. 110049/Z/15/Z)

Focusing the Neuroscience and Societal Implications of Cognitive Enhancers.

Cognitive enhancement can benefit the individual and society, but also has associated risks and ethical concerns. Cognitive-enhancing drugs are used in the treatment of neuropsychiatric disorders. Nonpharmacological strategies are also emerging, which have the potential to improve motivational deficits associated with neuropsychiatric symptoms and should be prioritized for development. The increasing lifestyle use of "smart" and other drugs indicates the desire for healthy people to improve themselves. Safety and ethical implications are discussed.Janssen/J&J, Wallitt FoundationThis is the author accepted manuscript. The final version is available from Wiley via http://dx.doi.org/10.1002/cpt.45

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Hypoactivation in right inferior frontal cortex is specifically associated with motor response inhibition in adult ADHD

Adult ADHD has been linked to impaired motor response inhibition and reduced associated activation in the right inferior frontal cortex (IFC). However, it is unclear whether abnormal inferior frontal activation in adult ADHD is specifically related to a response inhibition deficit or reflects a more general deficit in attentional processing. Using functional magnetic resonance imaging, we tested a group of 19 ADHD patients with no comorbidities and a group of 19 healthy control volunteers on a modified go/no-go task that has been shown previously to distinguish between cortical responses related to response inhibition and attentional shifting. Relative to the healthy controls, ADHD patients showed increased commission errors and reduced activation in inferior frontal cortex during response inhibition. Crucially, this reduced activation was observed when controlling for attentional processing, suggesting that hypoactivation in right IFC in ADHD is specifically related to impaired response inhibition. The results are consistent with the notion of a selective neurocognitive deficit in response inhibition in adult ADHD associated with abnormal functional activation in the prefrontal cortex, whilst ruling out likely group differences in attentional orienting, arousal and motivation