Addressing the needs of international postgraduate students: the role of social capital

Self-evidently, international students are likely to have considerable informational and social needs when coming to study in the UK. This paper reports the findings of a small study of such needs among international postgraduate students in the School of Health Sciences. It was an interview study, with twelve students participating. Though the study was designed to support the creation of an online resource, the findings suggest that meeting those needs satisfactorily requires a multi-faceted approach. Both face-to-face and online processes are needed to help students to develop the social capital necessary to success in undertaking the course, getting to know the university, and adjusting to life in England

Cognition-Enhancing Doses of Methylphenidate Preferentially Increase Prefrontal Cortex Neuronal Responsiveness

Background Despite widespread use of low-dose psychostimulants for the treatment of attention deficit hyperactivity disorder (ADHD), the neural basis for the therapeutic actions of these drugs are not well-understood. We recently demonstrated that low-dose methylphenidate (MPH) increases catecholamine efflux preferentially within the prefrontal cortex (PFC), suggesting the PFC is a principal site of action in the behavioral-calming and cognition-enhancing effects of low-dose psychostimulants. To better understand the neural mechanisms involved in the behavioral actions of low-dose stimulants, the current study examined the effects of low-dose MPH on the discharge properties of individual and ensembles of PFC neurons. Methods Extracellular activity of multiple individual PFC neurons was recorded in freely moving rats using multi-channel recording techniques. Behavioral studies identified optimal, working memory-enhancing doses of intraperitoneal MPH. The effects of these low-doses of MPH on PFC neuronal discharge properties were compared to: 1) the effects of high-dose MPH on PFC neuronal discharge; 2) the effects of low-dose MPH on neuronal discharge within the somatosensory cortex. Results Only working memory-enhancing doses of MPH increased the responsivity of individual PFC neurons and altered neuronal ensemble responses within the PFC. These effects were not observed outside the PFC (i.e. within somatosensory cortex). In contrast, high-dose MPH profoundly suppressed evoked discharge of PFC neurons. Conclusions These observations suggest that preferential enhancement of signal processing within the PFC, including alterations in the discharge properties of individual PFC neurons and PFC neuronal ensembles, underlie the behavioral/cognitive actions of low-dose psychostimulants

Psychostimulants as Cognitive Enhancers: The Prefrontal Cortex, Catecholamines and Attention Deficit Hyperactivity Disorder

Psychostimulants exert behavioral-calming and cognition-enhancing actions in the treatment of attention deficit hyperactivity disorder (ADHD). Contrary to early views, extensive research demonstrates that these actions are not unique to ADHD. Specifically, when administered at low and clinically-relevant doses, psychostimulants improve a variety of behavioral and cognitive processes dependent on the prefrontal cortex (PFC) in subjects with and without ADHD. Despite the longstanding clinical use of these drugs, the neural mechanisms underlying their cognition-enhancing/therapeutic actions have only recently begun to be examined. At behaviorally-activating doses, psychostimulants produce large and widespread increases in extracellular levels of brain catecholamines. In contrast, cognition-enhancing doses of psychostimulants exert regionally-restricted actions, elevating extracellular catecholamine levels and enhancing neuronal signal processing preferentially within the PFC. Additional evidence suggests a prominent role of PFC α2- and D1 receptors in the behavioral and electrophysiological actions of low-dose psychostimulants. These and other observations indicate a pivotal role of PFC catecholamines in the cognition-enhancing and therapeutic actions of psychostimulants as well as other drugs used in the treatment of ADHD. This information may be particularly relevant for the development of novel pharmacological treatments for ADHD and other conditions associated with PFC dysregulation

Stress-Induced Impairment of a Working Memory Task: Role of Spiking Rate and Spiking History Predicted Discharge

Stress, pervasive in society, contributes to over half of all work place accidents a year and over time can contribute to a variety of psychiatric disorders including depression, schizophrenia, and post-traumatic stress disorder. Stress impairs higher cognitive processes, dependent on the prefrontal cortex (PFC) and that involve maintenance and integration of information over extended periods, including working memory and attention. Substantial evidence has demonstrated a relationship between patterns of PFC neuron spiking activity (action-potential discharge) and components of delayed-response tasks used to probe PFC-dependent cognitive function in rats and monkeys. During delay periods of these tasks, persistent spiking activity is posited to be essential for the maintenance of information for working memory and attention. However, the degree to which stress-induced impairment in PFC-dependent cognition involves changes in task-related spiking rates or the ability for PFC neurons to retain information over time remains unknown. In the current study, spiking activity was recorded from the medial PFC of rats performing a delayed-response task of working memory during acute noise stress (93 db). Spike history-predicted discharge (SHPD) for PFC neurons was quantified as a measure of the degree to which ongoing neuronal discharge can be predicted by past spiking activity and reflects the degree to which past information is retained by these neurons over time. We found that PFC neuron discharge is predicted by their past spiking patterns for nearly one second. Acute stress impaired SHPD, selectively during delay intervals of the task, and simultaneously impaired task performance. Despite the reduction in delay-related SHPD, stress increased delay-related spiking rates. These findings suggest that neural codes utilizing SHPD within PFC networks likely reflects an additional important neurophysiological mechanism for maintenance of past information over time. Stress-related impairment of this mechanism is posited to contribute to the cognition-impairing actions of stress

Differential Sensitivity to Psychostimulants Across Prefrontal Cognitive Tasks: Differential Involvement of Noradrenergic α1- and α2-Receptors

BACKGROUND: Psychostimulants improve a variety of cognitive and behavioral processes in patients with attention-deficit/hyperactivity disorder (ADHD). Limited observations suggest a potentially different dose-sensitivity of prefrontal cortex (PFC)-dependent function (narrow inverted-U-shaped dose-response curves) versus classroom/overt behavior (broad inverted U) in children with ADHD. Recent work in rodents demonstrates that methylphenidate (MPH; Ritalin) elicits a narrow inverted-U-shaped improvement in performance in PFC-dependent tests of working memory. The current studies first tested the hypothesis that PFC-dependent tasks, in general, display narrow dose sensitivity to the beneficial actions of MPH. METHODS: The effects of varying doses of MPH were examined on performance of rats in two tests of PFC-dependent cognition, sustained attention and attentional set shifting. Additionally, the effect of pretreatment with the α₁-antagonist prazosin (.5 mg/kg) on MPH-induced improvement in sustained attention was examined. RESULTS: MPH produced a broad inverted-U-shaped facilitation of sustained attention and attentional set shifting. Prior research indicates α₁-receptors impair, whereas α₂-receptors improve, working memory. In contrast, attentional set shifting is improved with α₁-receptor activation, whereas α₂-receptors exert minimal effects in this task. Given the similar dose sensitivity of sustained attention and attentional set-shifting tasks, additional studies examined whether α₁-receptors promote sustained attention, similar to attentional set shifting. In these studies, MPH-induced improvement in sustained attention was abolished by α₁-receptor blockade. CONCLUSIONS: PFC-dependent processes display differential sensitivity to the cognition-enhancing actions of psychostimulants that are linked to the differential involvement of α₁- versus α₂-receptors in these processes. These observations have significant preclinical and clinical implications

Orbitofrontal cortex mediates pain inhibition by monetary reward

Pleasurable stimuli, including reward, inhibit pain, but the level of the neuraxis at which they do so and the cerebral processes involved are unknown. Here, we characterized a brain circuitry mediating pain inhibition by reward. Twenty-four healthy participants underwent functional magnetic resonance imaging while playing a wheel of fortune game with simultaneous thermal pain stimuli and monetary wins or losses. As expected, winning decreased pain perception compared to losing. Inter-individual differences in pain modulation by monetary wins relative to losses correlated with activation in the medial orbitofrontal cortex (mOFC). When pain and reward occured simultaneously, mOFCs functional connectivity changed: the signal time course in the mOFC condition-dependent correlated negatively with the signal time courses in the rostral anterior insula, anterior-dorsal cingulate cortex and primary somatosensory cortex, which might signify momentto-moment down-regulation of these regions by the mOFC. Monetary wins and losses did not change the magnitude of pain-related activation, including in regions that code perceived pain intensity when nociceptive input varies and/or receive direct nociceptive input. Pain inhibition by reward appears to involve brain regions not typically involved in nociceptive intensity coding but likely mediate changes in the significance and/or value of pain

Prefrontal Corticotropin-Releasing Factor (CRF) Neurons Act Locally to Modulate Frontostriatal Cognition and Circuit Function.

The PFC and extended frontostriatal circuitry support higher cognitive processes that guide goal-directed behavior. PFC-dependent cognitive dysfunction is a core feature of multiple psychiatric disorders. Unfortunately, a major limiting factor in the development of treatments for PFC cognitive dysfunction is our limited understanding of the neural mechanisms underlying PFC-dependent cognition. We recently demonstrated that activation of corticotropin-releasing factor (CRF) receptors in the caudal dorsomedial PFC (dmPFC) impairs higher cognitive function, as measured in a working memory task. Currently, there remains much unknown about CRF-dependent regulation of cognition, including the source of CRF for cognition-modulating receptors and the output pathways modulated by these receptors. To address these issues, the current studies used a viral vector-based approach to chemogenetically activate or inhibit PFC CRF neurons in working memory-tested male rats. Chemogenetic activation of caudal, but not rostral, dmPFC CRF neurons potently impaired working memory, whereas inhibition of these neurons improved working memory. Importantly, the cognition-impairing actions of PFC CRF neurons were dependent on local CRF receptors coupled to protein kinase A. Additional electrophysiological recordings demonstrated that chemogenetic activation of caudal dmPFC CRF neurons elicits a robust degradation of task-related coding properties of dmPFC pyramidal neurons and, to a lesser extent, medium spiny neurons in the dorsomedial striatum. Collectively, these results demonstrate that local CRF release within the caudal dmPFC impairs frontostriatal cognitive and circuit function and suggest that CRF may represent a potential target for treating frontostriatal cognitive dysfunction

The experience of long-term opiate maintenance treatment and reported barriers to recovery: A qualitative systematic review

Background/Aim: To inform understanding of the experience of long-term opiate maintenance and identify barriers to recovery. Methods: A qualitative systematic review. Results: 14 studies in 17 papers, mainly from the USA (65%), met inclusion criteria, involving 1,088 participants. Studies focused on methadone prescribing. Participants reported stability; however, many disliked methadone. Barriers to full recovery were primarily ‘inward focused'. Conclusion: This is the first review of qualitative literature on long-term maintenance, finding that universal service improvements could be made to address reported barriers to recovery, including involving ex-users as positive role models, and increasing access to psychological support. Treatment policies combining harm minimisation and abstinence-orientated approaches may best support individualised recovery

A common neural scale for the subjective pleasantness of different primary rewards.

When an economic decision is taken, it is between goals with different values, and the values must be on the same scale. Here, we used functional MRI to search for a brain region that represents the subjective pleasantness of two different rewards on the same neural scale. We found activity in the ventral prefrontal cortex that correlated with the subjective pleasantness of two fundamentally different rewards, taste in the mouth and warmth on the hand. The evidence came from two different investigations, a between-group comparison of two independent fMRI studies, and from a within-subject study. In the latter, we showed that neural activity in the same voxels in the ventral prefrontal cortex correlated with the subjective pleasantness of the different rewards. Moreover, the slope and intercept for the regression lines describing the relationship between activations and subjective pleasantness were highly similar for the different rewards. We also provide evidence that the activations did not simply represent multisensory integration or the salience of the rewards. The findings demonstrate the existence of a specific region in the human brain where neural activity scales with the subjective pleasantness of qualitatively different primary rewards. This suggests a principle of brain processing of importance in reward valuation and decision-making