Preliminary examination of the validity of the NIH toolbox cognition battery in treatment-resistant psychosis.

Objective: Prior research has suggested that treatment-resistant psychosis (TRP) may be a categorically distinct subtype from treatment-responsive psychotic disorders. However, relatively few studies have investigated the cognitive profile of individuals with TRP. Moreover, no prior studies have investigated the effectiveness of using the NIH Toolbox Cognition Battery (NTCB) for assessing cognition among psychiatric inpatients despite its promising efficiency and practicality in such settings. The current study aimed to investigate the validity of the NTCB and the associated cognitive profile of inpatients with TRP.Methods: Participants (N = 38) were administered the NTCB and a neuropsychological test battery. The Positive and Negative Syndrome Scale and the Routine Assessment of Patient Progress measured psychosis symptomatology and daily functioning, respectively.Results: Results showed deficits relative to normative values in fluid cognitive abilities using the NTCB, as predicted. There was strong convergent validity and adequate divergent validity between the NTCB subtests and corresponding neuropsychological measures, though no NTCB subtest correlated with performance on the Wisconsin Card Sorting Task. NTCB performance correlated with positive and disorganized symptoms of psychosis as well as daily functioning.Conclusions: Taken together, the NTCB appears to be a relatively strong tool for cognitive screening among psychiatric inpatients and may be used to identify which patients might benefit from further neuropsychological evaluation.

Characterization of mental health in cannabis dispensary users, using structured clinical interviews and standardized assessment instruments.

BACKGROUND: Cannabis is commonly used for its medical properties. In particular, cannabis is purported to have beneficial effects on a wide range of neuropsychiatric conditions. Studies assessing mental health in cannabis dispensary users typically evaluate symptoms using self-report check lists, which provide limited information about symptom severity, and whether subjects meet criteria for a psychiatric diagnosis. There is, therefore, a need for studies which assess mental health in dispensary users with standardized and well validated scientific instruments, such as those used in clinical drug trials. METHODS: One hundred medical cannabis users were recruited from a community dispensary. All subjects completed a structured clinical interview with the Mini-International Neuropsychiatric Interview (MINI). Subjects also completed the Perceived Stress Scale-10, PROMIS Fatigue Scale, PROMIS Sleep Disturbance Scale, Beck Depression Inventory, the Patient Health Questionnaire-15 and the Brief Pain Inventory. Details about cannabis use were also recorded. RESULTS: Lifetime prevalence of mental illness in this cohort was high, and a large proportion of subjects endorsed psychological symptoms. The proportion of subjects who met criteria for classification of a current psychiatric disorder was low for mood disorders, but high for anxiety disorders and substance abuse/dependence. Cannabis use differed between the main psychiatric conditions. CONCLUSIONS: The present results indicate that rates of mental illness may be high in medical cannabis dispensary users. Use of structured clinical assessments combined with standardized symptom severity questionnaires provide a feasible way to provide a more rigorous and detailed evaluation of conditions and symptoms in this population.

Working memory load improves diagnostic performance of smooth pursuit eye movement in mild traumatic brain injury patients with protracted recovery.

Smooth pursuit eye movements have been investigated as a diagnostic tool for mild traumatic brain injury (mTBI). However, the degree to which smooth pursuit differentiates mTBI patients from healthy controls (i.e. its diagnostic performance) is only moderate. Our goal was to establish if simultaneous performance of smooth pursuit and a working memory task increased the diagnostic performance of pursuit metrics following mTBI. We integrated an n-back task with two levels of working memory load into a pursuit target, and tested single- and dual-task pursuit in mTBI patients and healthy controls. We assessed pursuit using measures of velocity accuracy, positional accuracy and positional variability. The mTBI group had higher pursuit variability than the control group in all conditions. Performing a concurrent 1-back task decreased pursuit variability for both the mTBI and control groups. Performing a concurrent 2-back task produced differential effects between the groups: Pursuit variability was significantly decreased in the control group, but not in the mTBI group. Diagnostic indices were improved when pursuit was combined with the 2-back task, and increased by 20% for the most sensitive variable. Smooth pursuit with simultaneous working memory load may be a superior diagnostic tool for mTBI than measuring smooth pursuit alone.

Prenatal domoic acid exposure disrupts mouse pro-social behavior and functional connectivity MRI.

Domoic acid (DA) is a toxin produced by marine algae and known primarily for its role in isolated outbreaks of Amnestic Shellfish Poisoning and for the damage it inflicts on marine mammals, particularly California sea lions. Lethal effects of DA are often preceded by seizures and coma. Exposure to DA during development can result in subtle and highly persistent effects on brain development and include behavioral changes that resemble diagnostic features of schizophrenia and anomalies in social behavior we believe are relevant to autism spectrum disorder (ASD). To more fully examine this hypothesis, we chose to examine adolescent mice exposed in utero to DA for endpoints relevant to ASD, specifically changes in social behavior and network structure, the latter measured by resting state functional connectivity (rs-fcMRI). We found that male offspring exposed in utero to DA expressed reproducible declines in social interaction and atypical patterns of functional connectivity in the anterior cingulate, a region of the default mode network that is critical for social functioning. We also found disruptions in global topology in regions involved in the processing of reward, social, and sensory experiences. Finally, we found that DA exposed males expressed a pattern of local over-connectivity. These anomalies in brain connectivity bear resemblance to connectivity patterns in ASD and help validate DA-exposed mice as a model of this mental disability.

Prefrontal cortex and hippocampus in behavioural flexibility and posttraumatic functional recovery: reversal learning and set-shifting in rats.

Within one experiment and one T-maze, we examined the consequences of (i) bilateral lesions of the anteromedial prefrontal cortex (PFC), (ii) bilateral transections of the fimbria-fornix (FF), or (iii) combined lesions of both PFC and FF (COMB) on rats' ability to perform reversal or set-shifting. Postoperatively, the animals were trained to perform a spatial discrimination go-right task. This was followed by (1) a spatial reversal go-left task (reversal learning), or (2) a visual pattern discrimination task (set-shift). Neither single (PFC or FF) lesion nor combined (COMB) lesions affected the animals' ability to acquire the original spatial discrimination task. Regarding the reversal learning, the performance of the PFC and the FF groups was not significantly different from that of the sham operated control animals (Sham). In contrast, animals with combined lesion of both structures were impaired on both error rate and acquisition speed relative to all other groups. Regarding the set-shifting, all lesioned groups were impaired relative to the Sham group both regarding the error rate and the acquisition speed. There was, however, no difference in the degree of impairment between the lesioned groups. We conclude that both the PFC and the hippocampus contributed to the mediation of the reversal learning and set-shifting. During functional recovery of reversal learning, these two structures exhibited a mutual dependency, whilst the functional recovery of set-shifting was mediated by a substrate outside these two structures.

Delayed intensive acquisition training alleviates the lesion-induced place learning deficits after fimbria-fornix transection in the rat.

This study evaluates the effects of two learning paradigms, intensive vs. baseline, on the posttraumatic acquisition of a water maze based place learning task. Rats were subjected either to a control operation (Sham) or to a fimbria-fornix (FF) transection, which renders the hippocampus dysfunctional and disrupts the acquisition of allocentric place learning. All animals were administered 30 post-lesion acquisition sessions, which spanned either 10 or 30days. The acquisition period was followed by a 7day pause after which a retention probe was administered. The lesioned animals were divided into 3 groups: i) Baseline Acquisition Paradigm (BAP) once daily for 30days starting 1week post-surgery; ii) Early Intensive Acquisition Paradigm (EIAP) 3 times daily for 10days starting 1week post-surgery; and iii) Late Intensive Acquisition Paradigm (LIAP) 3 times daily for 10days starting 3weeks post-surgery. Within the control animals, one group followed the schedule of BAP, and one group followed the schedule of Intensive Acquisition Paradigm (IAP). All lesioned animals showed an impaired task acquisition. LIAP was beneficial in FF animals, in that it led to a better acquisition of the place learning task than the two other acquisition paradigms. The FF/EIAP group did not show improved acquisition compared to the FF/BAP group. The control animals were not differentially affected by the two learning schedules. The findings have implications for cognitive rehabilitation after brain injury and support the assumption that intensive treatment can lead to an improved learning, even when the neural structures underlying such a process are compromised. However, the timing of intensive treatment needs to be considered further.