This study examined the validity of the four standard psychological paradigms that have been operationally defined within the CogState brief computerized cognitive assessment battery. Construct validity was determined in a large group of healthy adults. CogState measures of processing speed, attention, working memory, and learning showed strong correlations with conventional neuropsychological measures of these same constructs (r's = .49 to .83). Criterion validity was determined by examining patterns of performance on the CogState tasks in groups of individuals with mild head injury, schizophrenia, and AIDS dementia complex. Each of these groups was impaired on the CogState performance measures (Cohen's d's = -.60 to -1.80) and the magnitude and nature of this impairment was qualitatively and quantitatively similar in each group. Taken together, the results suggest that the cognitive paradigms operationally defined in the CogState brief battery have acceptable construct and criterion validity in a neuropsychological context.

Our goal was to apply a statistical approach to allow the identification of atypical language patterns and to differentiate patients with epilepsy from healthy subjects, based on their cerebral activity, as assessed by functional MRI (fMRI). Patients with focal epilepsy show reorganization or plasticity of brain networks involved in cognitive functions, inducing ‘atypical’ (compared to ‘typical’ in healthy people) brain profiles. Moreover, some of these patients suffer from drug-resistant epilepsy, and they undergo surgery to stop seizures. The neurosurgeon should only remove the zone generating seizures and must preserve cognitive functions to avoid deficits. To preserve functions, one should know how they are represented in the patient’s brain, which is in general different from that of healthy subjects. For this purpose, in the pre-surgical stage, robust and efficient methods are required to identify atypical from typical representations. Given the frequent location of regions generating seizures in the vicinity of language networks, one important function to be considered is language. The risk of language impairment after surgery is determined pre-surgically by mapping language networks. In clinical settings, cognitive mapping is classically performed with fMRI. The fMRI analyses allowing the identification of atypical patterns of language networks in patients are not sufficiently robust and require additional statistic approaches. In this study, we report the use of a statistical nonlinear machine learning classification, the Extreme Gradient Boosting (XGBoost) algorithm, to identify atypical patterns and classify 55 participants as healthy subjects or patients with epilepsy. XGBoost analyses were based on neurophysiological features in five language regions (three frontal and two temporal) in both hemispheres and activated with fMRI for a phonological (PHONO) and a semantic (SEM) language task. These features were combined into 135 cognitively plausible subsets and further submitted to selection and binary classification. Classification performance was scored with the Area Under the receiver operating characteristic curve (AUC). Our results showed that the subset SEM_LH BA_47-21 (left fronto-temporal activation induced by the SEM task) provided the best discrimination between the two groups (AUC of 91 ± 5%). The results are discussed in the framework of the current debates of language reorganization in focal epilepsy.Electronic supplementary materialThe online version of this article (doi:10.1007/s40708-017-0065-7) contains supplementary material, which is available to authorized users.

Background: Psychosocial responses to infectious disease outbreaks have the potential to inflict acute and longstanding mental health consequences. Early research across the globe has found wide ranging psychological responses to the current COVID-19 pandemic. Understanding how different coping styles can be effective in mitigating mental ill health would enable better tailored psychological support. Aims: The aim of this study was to gain an understanding of psychosocial responses to the COVID-19 pandemic, including depression, anxiety and distress, as well as effective coping styles in an Australian sample. Method: A sample of 1,495 adults, residing in Australia between April 3rd and May 3rd 2020, completed an online survey which measured psychological distress (Impact of Events Scale-Revised), depression, anxiety, stress (DASS-21), as well as coping strategies (Brief COPE). Results: 47% of the respondents were experiencing some degree of psychological distress. Females experienced higher levels of depression, anxiety and stress than males. Coping strategies associated with better mental health were positive reframing, acceptance and humour. Conversely, self-blame, venting, behavioural disengagement and self-distraction were associated with poorer mental health. Conclusion: Rates of psychological symptoms amongst the Australian population are similar to those reported in other countries. Findings add to the growing literature demonstrating a gender disparity in the mental health impacts of COVID-19. Positive emotion focused coping strategies may be effective for reducing psychological symptoms. Understanding psychosocial responses including beneficial coping strategies are crucial to manage the current COVID-19 situation optimally, as well as to develop mental health response plans for future pandemics.

In order to investigate the physiological properties of the melanin-concentrating hormone (MCH) we have generated and used mice from which the MCH receptor 1 gene was deleted (MCHR1(Neo/Neo) mice). Complementary experimental approaches were used to investigate alterations in the learning and memory processes of our transgenic model. The ability of the knockout strain to carry out the inhibitory passive avoidance test was found to be considerably impaired although no significant differences were observed in anxiety levels. This impaired cognitive property prompted us to explore modifications in N-methyl D-aspartate (NMDA) responses in the hippocampus. Intracellular recordings of CA1 pyramidal neurons in hippocampal slices from the MCHR1(Neo/Neo) mice revealed significantly decreased NMDA responses. Finally, using in situ hybridization we found a 15% reduction in NMDAR1 subunit in the CA1 region. These results show for the first time a possible role for MCH in the control of the function of the NMDA receptor.

A vast body of experimental in vitro work and modelling studies suggests that the firing pattern and/or rate of a majority of midbrain dopaminergic neurons may be controlled in part by Ca2+-activated K+ channels of the SK type. However, due to the lack of suitable tools, in vivo evidence is lacking. We have taken advantage of the development of the water-soluble, medium potency SK blocker N-methyl-laudanosine (CH3-L) to test this hypothesis in anaesthetized rats. In the lateral ventral tegmental area, CH3-L iontophoresis onto dopaminergic neurons significantly increased the coefficient of variation of their interspike intervals and the percentage of spikes generated in bursts as compared to the control condition. The effect of CH3-L persisted in the presence of a specific GABA(A) antagonist, suggesting a direct effect. It was robust and reversible, and was also observed in the substantia nigra. Control experiments demonstrated that the effect of CH3-L could be entirely ascribed to its blockade of SK channels. On the other hand, the firing pattern of noradrenergic neurons was much less affected by CH3-L. We provide here the first demonstration of a major role of SK channels in the control of the switch between tonic and burst firing of dopaminergic neurons in physiological conditions. This study also suggests a new strategy to develop modulators of the dopaminergic (DA) system, which could be of interest in the treatment of Parkinson's disease, and perhaps other diseases in which DA pathways are dysfunctional.

Introduction: Theta burst pattern repetitive transcranial magnetic stimulation (TBS) is increasingly applied to treat depression. TBS's brevity is well-suited to application in accelerated schedules. Sizeable trials of accelerated TBS are lacking; and optimal TBS parameters such as stimulation intensity are not established. Methods: We conducted a three arm, single blind, randomised, controlled, multi-site trial comparing accelerated bilateral TBS applied at 80 % or 120 % of the resting motor threshold and left unilateral 10 Hz rTMS. 300 patients with treatment-resistant depression (TRD) were recruited. TBS arms applied 20 bilateral prefrontal TBS sessions over 10 days, while the rTMS arm applied 20 daily sessions of 10 Hz rTMS to the left prefrontal cortex over 4 weeks. Primary outcome was depression treatment response at week 4. Results: The overall treatment response rate was 43.7 % and the remission rate was 28.2 %. There were no significant differences for response (p ¼ 0.180) or remission (p ¼ 0.316) across the three groups. Response rates between accelerated bilateral TBS applied at sub-and supra-threshold intensities were not significantly different (p ¼ 0.319). Linear mixed model analysis showed a significant effect of time (p < 0.01), but not rTMS type (p ¼ 0.680). Conclusion: This is the largest accelerated bilateral TBS study to date and provides evidence that it is effective and safe in treating TRD. The accelerated application of TBS was not associated with more rapid antidepressant effects. Bilateral sequential TBS did not have superior antidepressant effect to unilateral 10 Hz rTMS. There was no significant difference in antidepressant efficacy between sub-and suprathreshold accelerated bilateral TBS.

Drug induced cognitive change is generally investigated using small sample sizes. In terms of null hypothesis significance testing (NHST) this can render a meaningful change non-significant, as a result of insufficient power in the statistical model. NHST leads to 'all or none' thinking, where a non-significant result is interpreted as an absence of change. An effect size calculation indicates the magnitude of change which has occurred post-intervention, and therefore whether a significant result is meaningful. We used a scopolamine challenge to demonstrate the usefulness of effect sizes. The aim of the study was to determine how effect sizes could describe the cognitive changes that occur following administration of subcutaneous scopolamine (s.c. scopolamine). Twenty four healthy young males (M = 32.6, sd = 4.5 years) were administered placebo and 0.2 mg, 0.4 mg & 0.6 mg of s.c. scopolamine using a 4-way crossover design. Memory, learning, psychomotor function, attention and executive function were assessed. Scopolamine significantly impaired performance on all tasks in a dose and time related manner. These results demonstrate the functionality of change scores to draw comparisons between different times and doses. This methodology overcomes the limitations of comparisons between studies using different tasks, doses and time at which cognitive functions are measured.

1 We have recently shown that the alkaloid methyl-laudanosine blocks SK channel-mediated afterhyperpolarizations (AHPs) in midbrain dopaminergic neurones. However, the relative potency of the compound on the SK channel subtypes and its ability to block AHPs of other neurones were unknown. 2 Using whole-cell patch-clamp experiments in transfected cell lines, we found that the compound blocks SK1, SK2 and SK3 currents with equal potency: its mean IC 50 s were 1.2, 0.8 and 1.8 mM, respectively. IK currents were unaffected. In rat brain slices, methyl-laudanosine blocked apaminsensitive AHPs in serotonergic neurones of the dorsal raphe and noradrenergic neurones of the locus coeruleus with IC 50 s of 21 and 19 mM, as compared to 15 mM in dopaminergic neurones. However, at 100 mM, methyl-laudanosine elicited a constant hyperpolarization of serotonergic neurones of about 9 mV, which was inconsistently (i.e. not in a reproducible manner) antagonized by atropine and hence partly due to the activation of muscarinic receptors. 3 While exploring the pharmacology of related compounds, we found that methyl-noscapine also blocked SK channels. In cell lines, methyl-noscapine blocked SK1, SK2 and SK3 currents with mean IC 50 s of 5.9, 5.6 and 3.9 mM, respectively. It also did not block IK currents. Methyl-noscapine was slightly less potent than methyl-laudanosine in blocking AHPs in brain slices, its IC 50 s being 42, 37 and 29 mM in dopaminergic, serotonergic and noradrenergic neurones, respectively. Interestingly, no significant non-SK effects were observed with methyl-noscapine in slices. At a concentration of 300 mM, methyl-noscapine elicited the same changes in excitability in the three neuronal types than did a supramaximal concentration of apamin (300 nM). 4 Methyl-laudanosine and methyl-noscapine produced a rapidly reversible blockade of SK channels as compared with apamin. The difference between the IC 50 s of apamin (0.45 nM) and methyllaudanosine (1.8 mM) in SK3 cells was essentially due to a major difference in their k À1 (0.028 s À1 for apamin and X20 s À1 for methyl-laudanosine). 5 These experiments demonstrate that both methyl-laudanosine and methyl-noscapine are medium potency, quickly dissociating, SK channel blockers with a similar potency on the three SK subtypes. Methyl-noscapine may be superior in terms of specificity for the SK channels.