The phytocannabinoid Δ9-tetrahydrocannabivarin modulates inhibitory neurotransmission in the cerebellum

Background and purpose: The phytocannabinoid Delta(9)-tetrahydrocannabivarin (Delta(9)-THCV) has been reported to exhibit a diverse pharmacology; here, we investigate functional effects of Delta(9)-THCV, extracted from Cannabis sativa, using electrophysiological techniques to define its mechanism of action in the CNS. Experimental approach: Effects of Delta(9)-THCV and synthetic cannabinoid agents on inhibitory neurotransmission at interneurone-Purkinje cell (IN-PC) synapses were correlated with effects on spontaneous PC output using single-cell and multi-electrode array (MEA) electrophysiological recordings respectively, in mouse cerebellar brain slices in vitro. Key results: The cannabinoid receptor agonist WIN 55,212-2 (WIN55) decreased miniature inhibitory postsynaptic current (mIPSC) frequency at IN-PC synapses. WIN55-induced inhibition was reversed by Delta(9)-THCV, and also by the CB1 receptor antagonist AM251; Delta(9)-THCV or AM251 acted to increase mIPSC frequency beyond basal values. When applied alone, Delta(9)-THCV, AM251 or rimonabant increased mIPSC frequency. Pre-incubation with Delta(9)-THCV blocked WIN55-induced inhibition. In MEA recordings, WIN55 increased PC spike firing rate; Delta(9)-THCV and AM251 acted in the opposite direction to decrease spike firing. The effects of Delta(9)-THCV and WIN55 were attenuated by the GABA(A) receptor antagonist bicuculline methiodide. Conclusions and implications: We show for the first time that Delta(9)-THCV acts as a functional CB1 receptor antagonist in the CNS to modulate inhibitory neurotransmission at IN-PC synapses and spontaneous PC output. Delta(9)-THCV- and AM251-induced increases in mIPSC frequency beyond basal levels were consistent with basal CB1 receptor activity. WIN55-induced increases in PC spike firing rate were consistent with synaptic disinhibition; whilst Delta(9)-THCV-and AM251-induced decreases in spike firing suggest a mechanism of PC inhibition.

The multidimensional measurement of the positive symptoms of psychosis

The measures most frequently used to assess psychotic symptoms fail to reflect important dimensions. The Psychotic Symptom Rating Scale (PSYRATS) aims to capture the multidimensional nature of auditory hallucinations and delusions. Individuals (N = 276) who had recently relapsed with positive symptoms completed the auditory hallucinations and delusions PSYRATS scales. These scores were compared with the relevant items from the SAPS and PANSS, and with measures of current mood. Total scores and distribution of items of the PSYRATS scales are presented and correlated with other measures. Positive symptom items from the SAPS and PANSS reflected the more objective aspects of PSYRATS ratings of auditory hallucinations and delusions (frequency and conviction) but were relatively poor at measuring distress. A major strength of the PSYRATS scales is the specific measurement of the distress dimension of symptoms, which is a key target of psychological intervention. It is advised that the PSYRATS should not be used as a total score alone, whilst further research is needed to clarify the best use of potential subscales. Copyright (c) 2007 John Wiley & Sons, Ltd.

Family interventions in psychosis: a scale to measure therapist adherence

The efficacy of family interventions in psychosis is well documented. UK and USA schizophrenia treatment guidelines advocate the practice of family interventions within routine clinical services. However, less attention has been paid to the study of treatment fidelity and the tools used in its assessment. This study reports the inter-rater reliability of a new scale: Family Intervention in Psychosis-Adherence Scale (FIPAS). This measure is designed to assess therapist adherence to the Kuipers et al. (2002) family intervention in psychosis treatment manual. Reliability ratings were based on a sample of thirteen audiotapes drawn from a randomized controlled trial of family intervention. The results indicated that the majority of items of the FIPAS had acceptable levels of inter-rater reliability. The findings are discussed in terms of their implications for the training and monitoring of the effectiveness of practitioners for family interventions in psychosis.

Deficient acquisition and consolidation: intertrial free recall performance in Alzheimer's disease and mild cognitive impairment

Previous research demonstrates that dementia of the Alzheimer type (DAT) is characterised by deficits of episodic memory, especially in the acquisition of new material. As well as this deficit in acquisition, some researchers have also argued for a deficit in consolidation in DAT. We examined acquisition and consolidation by measuring the intertrial gained and lost access in DAT, Mild Cognitive Impairment (MCI) and controls. We report findings from a study of clinical data based on assessment of patients using three free recall trials of a word list. We found that both DAT and MCI groups showed a deficit in acquisition and consolidation of items between trials relative to controls. Moreover, the DAT group was significantly impaired relative to the MCI group for both acquisition and consolidation. Correlations within each group showed that there were strong relationships between intertrial measures and standard measures of memory function. Importantly in no group was there a significant correlation between our measures of acquisition and consolidation: we argue that these measures reflect different underlying processes, and the failure to consolidate in DAT and MCI is not related to the deficit in acquisition. Finally, we showed strong correlations between our measure and dementia severity, suggesting that acquisition and consolidation both get worse as the dementia progresses.

The intention-superiority effect for naturally occurring activities: the role of intention accessibility in everyday prospective remembering in young and older adults

This study examined age differences in the accessibility of a single pool of naturally occurring intentions both before and after completion. Following Maylor, Darby, and Della Sala (2000), accessibility was measured in terms of the number of activities generated in a 4-minute activity fluency task. Each participant undertook two such tasks. A prospective task in which they generated activities intended for completion during the following week and a retrospective task, I week later, in which they generated activities carried out over the previous week. In a partial replication of Maylor et al.'s findings, young, but not healthy older, adults generated more to-be-completed intentions than completed ones, demonstrating an intention-superiority effect (ISE) for everyday activities. The absence of an ISE for older adults appeared to reflect the reduced accessibility of intentions prior to completion, rather than the impaired inhibition of fulfilled intentions. Moreover, both groups showed greater inaccessibility of completed than intended activities, thus demonstrating an intentioncompletion effect for naturally occurring intentions that is preserved in healthy ageing (cf. Marsh, Hicks, & Bink, 1998). Despite showing a reduced accessibility of intended activities, older adults reported having completed a greater proportion of their intentions during the week than young adults. Moreover, there was a correlation between the ability to access intentions and the proportion of intentions completed only for young adults. These observations suggest that older adults' everyday prospective memory performance may be relatively less dependent on intention accessibility and more dependent on other factors. While there was no age difference in the reported use and effectiveness of external retrieval aids, older adults demonstrated a greater level of temporal organization in the production of their intentions in the fluency task. This is consistent with the possibility that older adults may have more structured daily lives and may be able to use information about the sequence of ongoing events to support superior everyday prospective remembering.

The representation of delayed intentions: a prospective subject-performed task?

To-be-enacted material is more accessible in tests of recognition and lexical decision than material not intended for action (T. Goschke J. Kuhl, 1993; R. L. Marsh, J. L. Hicks, & M. L. Bink, 1998). This finding has been attributed to the superior status of intention-related information. The current article explores an alternative (action-superiority) account that draws parallels between the intended enactment effect (IEE) and the subject-performed task effect. Using 2 paradigms, the authors observed faster recognition latencies for both enacted and to-be-enacted material. It is crucial to note that there was no evidence of an IEE for items that had already been executed during encoding. The IEE was also eliminated when motor processing was prevented after verbal encoding. These findings suggest an overlap between overt and intended enactment and indicate that motor information may be activated for verbal material in preparation for subsequent execution.

Aging and the accessibility of performed and to-be-performed actions

In young adults information designated for future enactment is more readily accessible from memory than information not intended for enactment (e.g. Goschke & Kuhl, 1993). We examined whether this advantage for to-be-enacted material is reduced in older adults and thus whether attenuated action accessibility could underlie age-associated declines in prospective remembering. Young and older adults showed an equivalent increase in accessibility (faster recognition latencies) for to-be-enacted items over items intended for verbal report. Both age groups also showed increased accessibility for actions performed at encoding compared with verbally encoded items. Moreover, these effects were non-additive, suggesting similarities in the representation of completed and to-be-completed actions.

Motor brain regions are involved in the encoding of delayed intentions: a fMRI study

In studies of prospective memory, recall of the content of delayed intentions is normally excellent, probably because they contain actions that have to be enacted at a later time. Action words encoded for later enactment are more accessible from memory than those encoded for later verbal report [Freeman, J.E., and Ellis, J.A. 2003a. The representation of delayed intentions: A prospective subject-performed task? Journal of Experimental Psychology: Learning, Memory, and Cognition, 29, 976-992.]. As this higher assessibility is lost when the intended actions have to be enacted during encoding, or when a motor interference task is introduced concurrent to intention encoding, Freeman and Ellis suggested that the advantage of to-be-enacted actions is due to additional preparatory motor operations during encoding. Accordingly, in a fMRI study with 10 healthy young participants, we investigated whether motor brain regions are differentially activated during verbal encoding of actions for later enactment with the right hand in contrast to verbal encoding of actions for later verbal report. We included an additional condition of verbal encoding of abstract verbs for later verbal report to investigate whether the semantic motor information inherent in action verbs in contrast to abstract verbs activates motor brain regions different from those involved in the verbal encoding of actions for later enactment. Differential activation for the verbal encoding of to-be-enacted actions in contrast to to-be-reported actions was found in brain regions known to be involved in covert motor preparation for hand movements, i.e. the postcentral gyrus, the precuneus, the dorsal and ventral premotor cortex, the posterior middle temporal gyrus and the inferior parietal lobule. There was no overlap between these brain regions and those differentially activated during the verbal encoding of actions in contrast to abstract verbs for later verbal report. Consequently, the results of this fMRI study suggest the presence of preparatory motor operations during the encoding of delayed intentions requiring a future motor response, which cannot be attributed to semantic information inherent to action verbs. (c) 2006 Elsevier B.V. All rights reserved.

Modelling bi-directional research: a fresh approach to stakeholder theory

Purpose – While Freeman's stakeholder management approach has attracted much attention from both scholars and practitioners, little empirical work has considered the interconnectedness of organisational perspectives and stakeholder perspectives. The purpose of this paper is to respond to this gap by developing and empirically testing a bi-directional model of organisation/stakeholder relationships. Design/methodology/approach – A conceptual framework is developed that integrates how stakeholders are affected by organisations with how they affect organisations. Quantitative data relating to both sides of the relationship are obtained from 700 customers of a European service organisation and analysed using partial least squares structural equation modelling technique. Findings – The findings provide empirical support for the notion of mutual dependency between organisations and stakeholders as advocated by stakeholder theorists. The results suggest that the way stakeholders relate to organisations is dependent on how organisations relate to stakeholders. Originality/value – The study is original on two fronts: first, it provides a framework and process that can be used by researchers to model bi-directional research with other stakeholder groups and in different contexts. Second, the study presents an example application of bi-directional research by empirically linking organisational and stakeholder expectations in the case of customers of a UK service organisation.