Impulsive choice in hippocampal but not orbitofrontal cortex-lesioned rats on a nonspatial decision-making maze task

Orbitofrontal cortical (OFC) and hippocampal (HPC) lesions in primates and rodents have been associated with impulsive behaviour. We showed previously that OFC- or HPC-lesioned rats chose the immediate low-reward (LR) option in preference to the delayed high-reward (HR) option, where LR and HR were associated with different spatial responses in a uniform grey T-maze. We now report that on a novel nonspatial T-maze task in which the HR and LR options are associated with patterned goal arms (black-and-white stripes vs. gray), OFC-lesioned rats did not show impulsive behaviour, choosing the delayed HR option, and were indistinguishable from controls. In contrast, HPC-lesioned rats exhibited impulsive choice in the nonspatial decision-making task, although they chose the HR option on the majority of trials when there was a 10-s delay associated with both goal arms. The previously reported impairment in OFC-lesioned rats on the spatial version of the intertemporal choice task is unlikely to reflect a general problem with spatial learning, because OFC lesions were without effect on acquisition of the standard reference memory water-maze task and spatial working memory performance (nonmatching-to-place) on the T-maze. The differential effect of OFC lesions on the two versions of the intertemporal choice task may be explained instead in terms of the putative role of OFC in using associative information to represent expected outcomes and generate predictions. The impulsivity in HPC-lesioned rats may reflect impaired temporal information processing, and emphasizes a role for the hippocampus beyond the spatial domain

Inferring brain-wide interactions using data-constrained recurrent neural network models

Behavior arises from the coordinated activity of numerous anatomically and functionally distinct brain regions. Modern experimental tools allow unprecedented access to large neural populations spanning many interacting regions brain-wide. Yet, understanding such large-scale datasets necessitates both scalable computational models to extract meaningful features of inter-region communication and principled theories to interpret those features. Here, we introduce Current-Based Decomposition (CURBD), an approach for inferring brain-wide interactions using data-constrained recurrent neural network models that directly reproduce experimentally-obtained neural data. CURBD leverages the functional interactions inferred by such models to reveal directional currents between multiple brain regions. We first show that CURBD accurately isolates inter-region currents in simulated networks with known dynamics. We then apply CURBD to multi-region neural recordings obtained from mice during running, macaques during Pavlovian conditioning, and humans during memory retrieval to demonstrate the widespread applicability of CURBD to untangle brain-wide interactions underlying behavior from a variety of neural datasets

Satisfaction is not all – patients' perceptions of outcome of general practice consultations, a qualitative study

BACKGROUND: Evaluation of outcome in general practice can be seen from different viewpoints. In this study we focus on the concepts patients use to describe the outcome of a consultation with a GP. METHOD: Patients were interviewed within a week after a consultation with a GP. The interviews were made with 20 patients in 5 focus groups and 8 individually. They were analysed with a phenomenographic research approach. RESULTS: From the patient's perspective, the outcome of a consultation is about cure or symptom relief, understanding, confirmation, reassurance, change in self-perception and satisfaction. CONCLUSION: General practice consultations are often more important for patients than generally supposed. Understanding is the most basic concept

"I did not intend to stop. I just could not stand cigarettes any more." A qualitative interview study of smoking cessation among the elderly

<p>Abstract</p> <p>Background</p> <p>Every year, more than 650,000 Europeans die because they smoke. Smoking is considered to be the single most preventable factor influencing health. General practitioners (GP) are encouraged to advise on smoking cessation at all suitable consultations. Unsolicited advice from GPs results in one of 40-60 smokers stopping smoking. Smoking cessation advice has traditionally been given on an individual basis. Our aim was to gain insights that may help general practitioners understand why people smoke, and why smokers stop and then remain quitting and, from this, to find fruitful approaches to the dialogue about stopping smoking.</p> <p>Methods</p> <p>Interviews with 18 elderly smokers and ex-smokers about their smoking and decisions to smoke or quit were analysed with qualitative content analysis across narratives. A narrative perspective was applied.</p> <p>Results</p> <p>Six stages in the smoking story emerged, from the start of smoking, where friends had a huge influence, until maintenance of the possible cessation. The informants were influenced by "all the others" at all stages. Spouses had vital influence in stopping, relapses and continued smoking. The majority of quitters had stopped by themselves without medication, and had kept the tobacco handy for 3-6 months. Often smoking cessation seemed to happen unplanned, though sometimes it was planned. With an increasingly negative social attitude towards smoking, the informants became more aware of the risks of smoking.</p> <p>Conclusion</p> <p>"All the others" is a clue in the smoking story. For smoking cessation, it is essential to be aware of the influence of friends and family members, especially a spouse. People may stop smoking unplanned, even when motivation is not obvious. Information from the community and from doctors on the negative aspects of smoking should continue. Eliciting life-long smoking narratives may open up for a fruitful dialogue, as well as prompting reflection about smoking and adding to the motivation to stop.</p

Structural and functional papez circuit integrity in amyotrophic lateral sclerosis

Cognitive impairment in amyotrophic lateral sclerosis (ALS) is heterogeneous but now recognized as a feature in non-demented patients and no longer exclusively attributed to executive dysfunction. However, despite common reports of temporal lobe changes and memory deficits in ALS, episodic memory has been less explored. In the current study, we examined how the Papez circuit—a circuit known to participate in memory processes—is structurally and functionally affected in ALS patients (n = 20) compared with healthy controls (n = 15), and whether these changes correlated with a commonly used clinical measure of episodic memory. Our multimodal MRI approach (cortical volume, voxel-based morphometry, diffusion tensor imaging and resting state functional magnetic resonance) showed reduced gray matter in left hippocampus, left entorhinal cortex and right posterior cingulate as well as increased white matter fractional anisotropy and decreased mean diffusivity in the left cingulum bundle (hippocampal part) of ALS patients compared with controls. Interestingly, thalamus, mammillary bodies and fornix were preserved. Finally, we report a decreased functional connectivity in ALS patients in bilateral hippocampus, bilateral anterior and posterior parahippocampal gyrus and posterior cingulate. The results revealed that ALS patients showed statistically significant structural changes, but more important, widespread prominent functional connectivity abnormalities across the regions comprising the Papez circuit. The decreased functional connectivity found in the Papez network may suggest these changes could be used to assess risk or assist early detection or development of memory symptoms in ALS patients even before structural changes are established

Abnormal Frontostriatal Activity During Unexpected Reward Receipt in Depression and Schizophrenia: Relationship to Anhedonia.

Alterations in reward processes may underlie motivational and anhedonic symptoms in depression and schizophrenia. However it remains unclear whether these alterations are disorder-specific or shared, and whether they clearly relate to symptom generation or not. We studied brain responses to unexpected rewards during a simulated slot-machine game in 24 patients with depression, 21 patients with schizophrenia, and 21 healthy controls using functional magnetic resonance imaging. We investigated relationships between brain activation, task-related motivation, and questionnaire rated anhedonia. There was reduced activation in the orbitofrontal cortex, ventral striatum, inferior temporal gyrus, and occipital cortex in both depression and schizophrenia in comparison with healthy participants during receipt of unexpected reward. In the medial prefrontal cortex both patient groups showed reduced activation, with activation significantly more abnormal in schizophrenia than depression. Anterior cingulate and medial frontal cortical activation predicted task-related motivation, which in turn predicted anhedonia severity in schizophrenia. Our findings provide evidence for overlapping hypofunction in ventral striatal and orbitofrontal regions in depression and schizophrenia during unexpected reward receipt, and for a relationship between unexpected reward processing in the medial prefrontal cortex and the generation of motivational states.Supported by a MRC Clinician Scientist award (G0701911), a Brain and Behaviour Research Foundation Young Investigator, and an Isaac Newton Trust award to Dr Murray; an award to Dr Segarra from the Secretary for Universities and Research of the Ministry of Economy and Knowledge of the Government of Catalonia and the European Union; by the University of Cambridge Behavioural and Clinical Neuroscience Institute, funded by a joint award from the Medical Research Council and Wellcome Trust (G1000183 and 093875/Z/10Z respectively); by awards from the Wellcome Trust (095692) and the Bernard Wolfe Health Neuroscience Fund to Professor Fletcher, and by awards from the Wellcome Trust Institutional Strategic Support Fund (097814/Z/11) and Cambridge NIHR Biomedical Research Centre. The authors are grateful for the help of clinical staff in CAMEO, in the Cambridge Rehabilitation and Recovery service and Pathways, and in the Cambridge IAPT service, for help with participant recruitment.This is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/npp.2015.37

Global reward state affects learning and activity in raphe nucleus and anterior insula in monkeys

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Emplotment as Epic in Archaeological Writing: The Site Monograph as Narrative

To emplot a narrative as epic is to present a story of vast scope and multiple plots as a legitimate member of a tradition of other such stories. This article argues that emplotment as epic is the broadest of three levels of plot in archaeological writings. At that level, the site monograph emerges as a characteristically archaeological form of narrative, fundamental to archaeology as a discipline and a source of chronic anxiety for archaeologists. The ‘stories’ told in site monographs are epic in length, diversity of materials covered and multiplicity of themes, plots and authors. Indeed, the more complexities of that sort the better, since those are features that help to emplot the work as good archaeology

Spatial Learning and Action Planning in a Prefrontal Cortical Network Model

The interplay between hippocampus and prefrontal cortex (PFC) is fundamental to spatial cognition. Complementing hippocampal place coding, prefrontal representations provide more abstract and hierarchically organized memories suitable for decision making. We model a prefrontal network mediating distributed information processing for spatial learning and action planning. Specific connectivity and synaptic adaptation principles shape the recurrent dynamics of the network arranged in cortical minicolumns. We show how the PFC columnar organization is suitable for learning sparse topological-metrical representations from redundant hippocampal inputs. The recurrent nature of the network supports multilevel spatial processing, allowing structural features of the environment to be encoded. An activation diffusion mechanism spreads the neural activity through the column population leading to trajectory planning. The model provides a functional framework for interpreting the activity of PFC neurons recorded during navigation tasks. We illustrate the link from single unit activity to behavioral responses. The results suggest plausible neural mechanisms subserving the cognitive “insight” capability originally attributed to rodents by Tolman & Honzik. Our time course analysis of neural responses shows how the interaction between hippocampus and PFC can yield the encoding of manifold information pertinent to spatial planning, including prospective coding and distance-to-goal correlates