Sidse Marie Arnfred

Gating of the vertex somatosensory and auditory evoked potential P50 and the correlation to skin conductance orienting response in healthy men

A defect in auditory evoked potential (AEP) P50 gating supports the theory of information-processing deficits in schizophrenia. The relationship between gating of the mid-latency evoked potentials (EP) in the somatosensory and the auditory modalities has not been studied together before. In schizophrenia, we might expect the processing deficits to act on multiple modalities. We have examined the gating of median nerve somatosensory EP (SEP) following paired stimulation identical to the AEP P50 gating paradigm using interstimulus intervals (ISI) of 500, 750 and 1000 ms and the correlation of gating to the skin conductance orienting response (SCOR) in 20 healthy men. We measured mid-latency vertex components (SEP: P50, N65, P85 and N100; AEP: P30, N45, P50 and N80). The gating was most pronounced at ISI 500 ms where the SEP P50 and N100 gating were 0.59 and 0.37, respectively, as compared to a gating of 0.61 in P30, 0.33 in P50 and 0.45 in N80 in the AEP. Repetition effects in the two modalities were not correlated. AEP P50 gating was correlated to skin conductance level (SCL). The combination of recording repetition effects on the mid-latency EP in two modalities could provide a method for investigating if deficits of information processing in schizophrenia are cross-modal.

Behavioral response to novelty correlates with dopamine receptor availability in striatum of Göttingen minipigs

Behavioral response to novelty in rats has been linked both to dopamine transmission in the ventral striatum, and to propensity to self-administer psychostimulant drugs. In order to probe the relationship between behavioral response to novelty and dopamine systems we have developed a behavioral model for correlation with positron emission tomography (PET) of dopamine transmission in brain of Göttingen minipigs. In the present study, we measured exploration of a novel object by recording the number of contacts, and duration of contact with a novel object, in groups of six male and six female adult minipigs. We hypothesized that these novelty scores would correlate with the amphetamine-evoked dopamine release in ventral striatum, measured 2 weeks later in a PET study of the availability of binding sites for the dopamine D2/3 antagonist [11C]raclopride. There were significant correlations between duration of contact with a novel object and the amphetamine-evoked reductions in binding potential (DeltapB) in the left ventral striatum of the 12 animals; Comparison of results by gender revealed that the correlation was driven mainly by the male group, and was not present in the female group. We interpret these results to show that propensity to explore an unfamiliar object is relatively elevated in pigs with low basal occupancy of dopamine D2/3 receptors by endogenous dopamine, and with high amphetamine-induced occupancy of released dopamine in the male pigs.

Mapping the amphetamine-evoked dopamine release in the brain of the Göttingen minipig

The availability of dopamine D(2/3) binding sites in brain of six male and six female Göttingen minipigs was measured in a baseline condition and after challenge with amphetamine sulfate (1mg/kg, i.v.) in PET studies with [(11)C]raclopride. Maps of the binding potential (pB; B(max)/K(d)) of [(11)C]raclopride were spatially normalized and co-registered to a common stereotaxic coordinate system for pig brain. The pB maps were then analyzed by volume of interest and voxel-wise comparisons of gender and condition. The mean baseline pB tended to be 10-20% higher in striatum of the female group, but this gender difference was not significant. Variance of the mean baseline pB was higher in the males (44%) than in females (30%), but there was no correlation between pB and individual plasma cortisol or testosterone concentrations. Using statistical parametric mapping, we detected a focus in the right posterior putamen where the magnitude of the amphetamine-evoked decrease in pB was greater in the male than in the female group. Thus, the spatial pattern of reactivity of dopamine D(2/3) receptor availability to amphetamine challenge is not identical in male and female pigs. Within the entire population, the decline in pB evoked by amphetamine (Delta pB) was greater in the ventral striatum (-28%) than in the caudate nucleus (-17%), consistent with earlier reports in monkeys and humans. The magnitude of Delta pB correlated highly with the baseline pB values in all divisions of the striatum. Based upon the principles of competitive binding, the slope of this empirical relationship, f(i), is equal to the fraction of [(11)C]raclopride binding sites sensitive to endogenous dopamine; the magnitude of this fraction ranged from 0.29 in the caudate to 0.36 in the ventral striatum.

Discriminations, reversals, and extra-dimensional shifts in the Göttingen minipig

Göttingen minipigs were trained on a set-shifting procedure involving discriminations, reversals, and extra-dimensional shifts. The discriminations used were black-white discriminations and right-left discriminations. The initial visual and spatial discrimination seemed equally difficult, and only for the visual modality was reversal found to be more difficult than the initial discrimination. Visual reversal was more difficult than spatial reversal, and a larger number of perseverative sessions were found for visual reversal compared to spatial reversal. The acquisition of the extra-dimensional shift from the visual to the spatial dimension was not inferior to the learning of spatial reversal. Neither was the acquisition of the extra-dimensional shift from the spatial to the visual dimension inferior to the learning of visual reversal. Thus, no evidence was found for attention to stimulus dimensions in discrimination learning of the pigs.

A mixed modality paradigm for recording somatosensory and auditory P50 gating

Significant somatosensory evoked potential (SEP) P50 gating has previously been found in young healthy men by the use of identical paired stimuli. In this study, the exploration of the gating paradigm was extended with the addition of a mixed modality paradigm where three different pairs of identical stimuli (clicks, right median nerve electric stimulations and proprioceptive stimuli of changing load on a handheld weight) were presented over a 12-s cycle. In both modalities repeated measures analyses of variance demonstrated no effect of paradigm. This mixed-modality recording paradigm could be used in further experiments to examine gating deficits across modalities.

Acquisition of visually guided conditional associative tasks in Göttingen minipigs

Fourteen Göttingen minipigs were trained on two different visually guided conditional associative tasks. In a spatial conditional task, a black stimulus signalled that a response to the left was correct, and a white stimulus signalled that a response to the right was correct. In a conditional go/no-go task, a blue stimulus signalled go, and a red stimulus signalled no-go. The pigs were trained until a behavioural criterion of 90% correct for each of two consecutive sessions. For the spatial conditional task, all pigs reached this criterion in 520 trials or less. For the conditional go/no-go task, all pigs, except three, reached this criterion in 1600 trials or less. Sows and boars learned equally fast. The tasks can be useful for the testing of cognitive function in pig models of human brain disorders.

Recovery-Oriented Practice in Mental Health Inpatient Settings: A Literature Review

OBJECTIVE Implementation of recovery-oriented practice has proven to be challenging, and little is known about the extent to which recovery-oriented principles are integrated into mental health inpatient settings. This review of the literature examined the extent to which a recovery-oriented approach is an integrated part of mental health inpatient settings. METHODS A systematic search (2000-2014) identified quantitative and qualitative studies that made explicit reference to the concept of recovery and that were conducted in adult mental health inpatient settings or that used informants from such settings. The quality and relevance of the studies were assessed with the Critical Appraisal Skills Program, and a text-driven content analysis identified three organizing themes: definitions and understandings, current practice, and challenges. RESULTS Eight studies from Canada, the United Kingdom, the United States, Australia, and Ireland were included. The results highlight the limited number of studies of recovery-oriented practice in mental health inpatient settings and the limited extent to which such an approach is integrated into these settings. Findings raise the question of whether recovery-oriented practice can or should be an approach used in these settings, which are primarily aimed at stabilization and symptom relief. CONCLUSIONS Research is needed to clarify the concept of recovery and how it applies to mental health inpatient settings. The challenges to recovery-oriented practice posed by the current organization of such settings should be examined.

Prevalence of delirium among patients at a cancer ward: Clinical risk factors and prediction by bedside cognitive tests

ABSTRACT Background Delirium is a frequent psychiatric complication to cancer, but rarely recognized by oncologists. Aims 1. To estimate the prevalence of delirium among inpatients admitted at an oncological cancer ward 2. To investigate whether simple clinical factors predict delirium 3. To examine the value of cognitive testing in the assessment of delirium. Methods On five different days, we interviewed and assessed patients admitted to a Danish cancer ward. The World Health Organization International Classification of Diseases Version 10, WHO ICD-10 Diagnostic System and the Confusion Assessment Method (CAM) were used for diagnostic categorization. Clinical information was gathered from medical records and all patients were tested with Mini Cognitive Test, The Clock Drawing Test, and the Digit Span Test. Results 81 cancer patients were assessed and 33% were diagnosed with delirium. All delirious participants were CAM positive. Poor performance on the cognitive tests was associated with delirium. Medical records describing CNS metastases, benzodiazepine or morphine treatment were associated with delirium. Conclusions Delirium is prevalent among cancer inpatients. The Mini Cognitive Test, The Clock Drawing Test, and the Digit Span Test can be used as screening tools for delirium among inpatients with cancer, but even in synergy, they lack specificity. Combining cognitive testing and attention to nurses’ records might improve detection, yet further studies are needed to create a more detailed patient profile for the detection of delirium.

Minipig negative slow wave demonstrates target/nontarget differences in P300 paradigm.

The negative slow wave (NSW) is a late component of the event-related potential (ERP) in man modulated like the P300 by the stimulus, the task, and the response demand. Aiming at the development of a minipig model of schizophrenia, we investigated scalp ERPs in an auditory P300 paradigm in six Göttingen minipigs. Before training, we observed no difference between target and nontarget NSW. After training, target NSW amplitude was increased 50% compared to nontarget. A P350 was recognized, but the finding of a lack of target/nontarget difference is not conclusive.

Transdiagnostic group CBT for anxiety disorders: the unified protocol in mental health services

Abstract Comorbidity among the anxiety disorders is common and may negatively impact treatment outcome. Potentially, transdiagnostic cognitive-behavioral treatments (CBT) deal more effectively with comorbidity than standard CBT. The present study tested the effectiveness of The Unified Protocol (UP) applied to Mental Health Services. Pre-post-treatment effects were examined for psychiatric outpatients with anxiety disorders receiving UP treatment in groups. Forty-seven patients (mean-age = 34.1 (SD = 9.92), 77% females) with a principal diagnosis of anxiety were included. We found significant and clinically meaningful changes in the primary outcomes Clinical Global Impression Severity Scale (CGI-S; d = 1.36), Hamilton Anxiety Scale (HARS; d = .71), and WHO-5 Well-being Index (WHO-5; d = .54). Also, comorbid depressive symptoms and levels of positive and negative affect changed significantly after treatment. Patients with high levels of comorbidity profited as much as patients with less comorbidity; however, these patients had higher scores after treatment due to higher symptom burden at onset. Patients with comorbid depression profited more from treatment than patients without comorbid depression. The treatment effects found in the present study correspond to treatment effects of other TCBT studies, other UP group studies, and effectiveness studies on standard CBT for outpatients. The results indicate that the UP can be successfully applied to a MHS group setting, demonstrating positive effects on anxiety and depressive symptoms for even highly comorbid cases.