Sleep disturbances comparable with insomnia occur in up to 80% of people with schizophrenia, but very little is known about the contribution of circadian coordination to these prevalent disruptions.
...A systematic exploration of circadian time patterns in individuals with schizophrenia with recurrent sleep disruption.
We examined the relationship between sleep-wake activity, recorded actigraphically over 6 weeks, along with ambient light exposure and simultaneous circadian clock timing, by collecting weekly 48 h profiles of a urinary metabolite of melatonin in 20 out-patients with schizophrenia and 21 healthy control individuals matched for age, gender and being unemployed.
Significant sleep/circadian disruption occurred in all the participants with schizophrenia. Half these individuals showed severe circadian misalignment ranging from phase-advance/delay to non-24 h periods in sleep-wake and melatonin cycles, and the other half showed patterns from excessive sleep to highly irregular and fragmented sleep epochs but with normally timed melatonin production.
Severe circadian sleep/wake disruptions exist despite stability in mood, mental state and newer antipsychotic treatment. They cannot be explained by the individuals' level of everyday function.
Collective evidence has strongly suggested that deep brain stimulation (DBS) is a promising therapy for Tourette syndrome.
To assess the efficacy and safety of DBS in a multinational cohort of ...patients with Tourette syndrome.
The prospective International Deep Brain Stimulation Database and Registry included 185 patients with medically refractory Tourette syndrome who underwent DBS implantation from January 1, 2012, to December 31, 2016, at 31 institutions in 10 countries worldwide.
Patients with medically refractory symptoms received DBS implantation in the centromedian thalamic region (93 of 163 57.1%), the anterior globus pallidus internus (41 of 163 25.2%), the posterior globus pallidus internus (25 of 163 15.3%), and the anterior limb of the internal capsule (4 of 163 2.5%).
Scores on the Yale Global Tic Severity Scale and adverse events.
The International Deep Brain Stimulation Database and Registry enrolled 185 patients (of 171 with available data, 37 females and 134 males; mean SD age at surgery, 29.1 10.8 years range, 13-58 years). Symptoms of obsessive-compulsive disorder were present in 97 of 151 patients (64.2%) and 32 of 148 (21.6%) had a history of self-injurious behavior. The mean (SD) total Yale Global Tic Severity Scale score improved from 75.01 (18.36) at baseline to 41.19 (20.00) at 1 year after DBS implantation (P < .001). The mean (SD) motor tic subscore improved from 21.00 (3.72) at baseline to 12.91 (5.78) after 1 year (P < .001), and the mean (SD) phonic tic subscore improved from 16.82 (6.56) at baseline to 9.63 (6.99) at 1 year (P < .001). The overall adverse event rate was 35.4% (56 of 158 patients), with intracranial hemorrhage occurring in 2 patients (1.3%), infection in 4 patients with 5 events (3.2%), and lead explantation in 1 patient (0.6%). The most common stimulation-induced adverse effects were dysarthria (10 6.3%) and paresthesia (13 8.2%).
Deep brain stimulation was associated with symptomatic improvement in patients with Tourette syndrome but also with important adverse events. A publicly available website on outcomes of DBS in patients with Tourette syndrome has been provided.
The "aberrant salience" model proposes that psychotic symptoms first emerge when chaotic brain dopamine transmission leads to the attribution of significance to stimuli that would normally be ...considered irrelevant. This is thought to occur during the prodromal phase of psychotic disorders, but this prediction has not been tested previously. In the present study, we tested this model in 18 healthy volunteers and 18 unmedicated individuals at ultra-high risk of psychosis. Subjects performed the Salience Attribution Test, which provides behavioral measures of adaptive and aberrant motivational salience, during functional magnetic resonance imaging to assess neural responses to relevant and irrelevant stimulus features. On a separate occasion, the same subjects were also studied with (18)Ffluorodopa positron emission tomography to measure dopamine synthesis capacity. Individuals at ultra-high risk of psychosis were more likely to attribute motivational salience to irrelevant stimulus features (t(26.7) = 2.8, P = .008), and this bias was related to the severity of their delusion-like symptoms (r = .62, P = .008). Ventral striatal responses to irrelevant stimulus features were also correlated with delusion-like symptoms in the ultra-high risk group (r = .59, P = .017). Striatal dopamine synthesis capacity correlated negatively with hippocampal responses to irrelevant stimulus features in ultra-high risk individuals, but this relationship was positive in controls. These data are consistent with the hypothesis that aberrant salience processing underlies psychotic symptoms and involves functional alterations in the striatum, hippocampus, and the subcortical dopamine system.
Multiple deep brain stimulation (DBS) targets have been proposed for treating intractable obsessive-compulsive disorder (OCD). Here, we investigated whether stimulation effects of different target ...sites would be mediated by one common or several segregated functional brain networks.
First, seeding from active electrodes of 4 OCD patient cohorts (N = 50) receiving DBS to anterior limb of the internal capsule or subthalamic nucleus zones, optimal functional connectivity profiles for maximal Yale-Brown Obsessive Compulsive Scale improvements were calculated and cross-validated in leave-one-cohort-out and leave-one-patient-out designs. Second, we derived optimal target-specific connectivity patterns to determine brain regions mutually predictive of clinical outcome for both targets and others predictive for either target alone. Functional connectivity was defined using resting-state functional magnetic resonance imaging data acquired in 1000 healthy participants.
While optimal functional connectivity profiles showed both commonalities and differences between target sites, robust cross-predictions of clinical improvements across OCD cohorts and targets suggested a shared network. Connectivity to the anterior cingulate cortex, insula, and precuneus, among other regions, was predictive regardless of stimulation target. Regions with maximal connectivity to these commonly predictive areas included the insula, superior frontal gyrus, anterior cingulate cortex, and anterior thalamus, as well as the original stereotactic targets.
Pinpointing the network modulated by DBS for OCD from different target sites identified a set of brain regions to which DBS electrodes associated with optimal outcomes were functionally connected—regardless of target choice. On these grounds, we establish potential brain areas that could prospectively inform additional or alternative neuromodulation targets for obsessive-compulsive disorder.
Deep brain stimulation (DBS) is an emerging treatment for severe obsessive-compulsive disorder (OCD). We compared the efficacy of ventral capsule/ventral striatal (VC/VS) and anteromedial subthalamic ...nucleus (amSTN) DBS in the same patients and tested for mechanistic differences on mood and cognitive flexibility and associated neural circuitry. The possible synergistic benefit of DBS at both sites and cognitive behavioral therapy was explored.
Six patients with treatment-refractory OCD (5 men; Yale-Brown Obsessive Compulsive Scale score >32) entered double-blind counterbalanced phases of 12-week amSTN or VC/VS DBS, followed by 12-week open phases when amSTN and VC/VS were stimulated together, in which optimal stimulation parameters were achieved and adjunctive inpatient cognitive behavioral therapy was delivered. OCD and mood were assessed with standardized scales and cognitive flexibility with the Cambridge Neuropsychological Test Automated Battery Intra-Extra Dimensional Set-Shift task. Diffusion-weighted and intraoperative magnetic resonance imaging scans were performed for tractography from optimally activated electrode contacts.
DBS at each site significantly and equivalently reduced OCD symptoms with little additional gain following combined stimulation. amSTN but not VC/VS DBS significantly improved cognitive flexibility, whereas VC/VS DBS had a greater effect on mood. The VC/VS effective site was within the VC. VC DBS connected primarily to the medial orbitofrontal cortex, and amSTN DBS to the lateral orbitofrontal cortex, dorsal anterior cingulate cortex, and dorsolateral prefrontal cortex. No further improvement followed cognitive behavioral therapy, reflecting a floor effect of DBS on OCD.
Both the VC/VS and amSTN are effective targets for severe treatment-refractory OCD. Differential improvements in mood and cognitive flexibility and their associated connectivity suggest that DBS at these sites modulates distinct brain networks.
These updated guidelines from the British Association for Psychopharmacology replace the original version published in 2011. They address the scope and targets of pharmacological treatment for ...schizophrenia. A consensus meeting was held in 2017, involving experts in schizophrenia and its treatment. They were asked to review key areas and consider the strength of the evidence on the risk-benefit balance of pharmacological interventions and the clinical implications, with an emphasis on meta-analyses, systematic reviews and randomised controlled trials where available, plus updates on current clinical practice. The guidelines cover the pharmacological management and treatment of schizophrenia across the various stages of the illness, including first-episode, relapse prevention, and illness that has proved refractory to standard treatment. It is hoped that the practice recommendations presented will support clinical decision making for practitioners, serve as a source of information for patients and carers, and inform quality improvement.
It has been postulated that impulsive-compulsive spectrum behaviors (ICBs) in Parkinson's disease (PD) reflect overvaluation of rewards, resulting from excessive dopaminergic transmission in the ...ventral striatum. However, as the ventral striatum is also strongly implicated in delay discounting, an alternative explanation would be that, similar to stimulant-dependent individuals, PD patients with ICBs impulsively discount future rewards. To test these hypotheses, we investigated whether 36 medicated PD patients with and without ICBs differed from controls on measures of stimulus-reinforcement learning and delay discounting. There was a clear double dissociation between reward learning and impulsivity in PD patients with and without ICBs. Although PD patients without ICBs were impaired at learning stimulus-reward associations for high-probability stimuli, PD patients with ICBs were able to learn such associations equally as well as controls. By contrast, PD patients with ICBs showed highly elevated delay discounting, whereas PD patients without ICBs did not differ from controls on this measure. These results contradict the hypothesis that ICBs in PD result from overvaluation of rewards. Instead, our data are more consistent with a model in which excessive dopaminergic transmission induces a strong preference for immediate over future rewards, driving maladaptive behavior in PD patients with ICBs.
Multiple surgical targets for treating obsessive-compulsive disorder with deep brain stimulation (DBS) have been proposed. However, different targets may modulate the same neural network responsible ...for clinical improvement. We analyzed data from four cohorts of patients (N = 50) that underwent DBS to the anterior limb of the internal capsule (ALIC), the nucleus accumbens or the subthalamic nucleus (STN). The same fiber bundle was associated with optimal clinical response in cohorts targeting either structure. This bundle connected frontal regions to the STN. When informing the tract target based on the first cohort, clinical improvements in the second could be significantly predicted, and vice versa. To further confirm results, clinical improvements in eight patients from a third center and six patients from a fourth center were significantly predicted based on their stimulation overlap with this tract. Our results show that connectivity-derived models may inform clinical improvements across DBS targets, surgeons and centers. The identified tract target is openly available in atlas form.
Schizophrenia is characterised by generalised cognitive impairment that is both a risk factor and a predictor of outcome. Recent research into human intelligence supports the view that, in ...schizophrenia, poor performance on disparate cognitive tasks can be explained by dysfunction of a frontoparietal neural network thought to support fluid intelligence.
Gilles de la Tourette syndrome (GTS) is a neurological condition characterized by motor and vocal tics. Previous studies suggested that this syndrome is associated with abnormal sensorimotor cortex ...activity at rest, as well as during the execution of voluntary movements. It has been hypothesized that this abnormality might be interpreted as a form of increased tonic inhibition, probably to suppress tics; however, this hypothesis has not been tested so far. The present study was designed to formally test how voluntary tic suppression in GTS influences the activity of the sensorimotor cortex during the execution of a motor task. We used EEG to record neural activity over the contralateral sensorimotor cortex during a finger movement task in adult GTS patients, in both free ticcing and tic suppression conditions; these data were then compared with those collected during the same task in age‐matched healthy subjects. We focused on the levels of activity in the beta frequency band, which is typically associated with the activation of the motor system, during three different phases: a pre‐movement, a movement, and a post‐movement phase. GTS patients showed decreased levels of beta modulation with respect to the healthy controls, during the execution of the task; however, this abnormal pattern returned to be normal when they were explicitly asked to suppress their tics while moving. This is the first demonstration that voluntary tic suppression in GTS operates through the normalization of the EEG rhythm in the beta frequency range during the execution of a voluntary finger movement.
We measured EEG in Gilles de la Tourette patients (GTS) and healthy controls. We tested whether tic inhibition influences the activity of the sensorimotor cortex during a motor task. GTS showed lower levels of beta modulation over the sensorimotor cortex during the execution of the task. This abnormal pattern returned to be normal during tic voluntary inhibition. We demonstrated that voluntary tic inhibition normalized the beta EEG rhythm of the sensorimotor cortex.
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