Anterior Hippocampus and Goal-Directed Spatial Decision Making

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The hippocampus and spatial constraints on mental imagery

We review a model of imagery and memory retrieval based on allocentric spatial representation by place cells and boundary vector cells (BVCs) in the medial temporal lobe, and their translation into egocentric images in retrosplenial and parietal areas. In this model, the activity of place cells constrain the contents of imagery and retrieval to be coherent and consistent with the subject occupying a single location, while the activity of head-direction cells along Papez's circuit determine the viewpoint direction for which the egocentric image is generated. An extension of this model is discussed in which a role for grid cells in dynamic updating of representations (mental navigation) is included. We also discuss the extension of this model to implement a version of the dual representation theory of post-traumatic stress disorder (PTSD) in which PTSD arises from an imbalance between weak allocentric hippocampal-mediated contextual representations and strong affective/sensory representations. The implications of these models for behavioral, neuropsychological, and neuroimaging data in humans are explored

Establishing the boundaries: the hippocampal contribution to imagining scenes

When we visualize scenes, either from our own past or invented, we impose a viewpoint for our “mind's eye” and we experience the resulting image as spatially coherent from that viewpoint. The hippocampus has been implicated in this process, but its precise contribution is unknown. We tested a specific hypothesis based on the spatial firing properties of neurons in the hippocampal formation of rats, that this region supports the construction of spatially coherent mental images by representing the locations of the environmental boundaries surrounding our viewpoint. Using functional magnetic resonance imaging, we show that hippocampal activation increases parametrically with the number of enclosing boundaries in the imagined scene. In contrast, hippocampal activity is not modulated by a nonspatial manipulation of scene complexity nor to increasing difficulty of imagining the scenes in general. Our findings identify a specific computational role for the hippocampus in mental imagery and episodic recollection

Consolidation of complex events via reinstatement in posterior cingulate cortex

It is well-established that active rehearsal increases the efficacy of memory consolidation. It is also known that complex events are interpreted with reference to prior knowledge. However, comparatively little attention has been given to the neural underpinnings of these effects. In healthy adult humans, we investigated the impact of effortful, active rehearsal on memory for events by showing people several short video clips and then asking them to recall these clips, either aloud (Experiment 1) or silently while in an MRI scanner (Experiment 2). In both experiments, actively rehearsed clips were remembered in far greater detail than unrehearsed clips when tested a week later. In Experiment 1, highly similar descriptions of events were produced across retrieval trials, suggesting a degree of semanticization of the memories had taken place. In Experiment 2, spatial patterns of BOLD signal in medial temporal and posterior midline regions were correlated when encoding and rehearsing the same video. Moreover, the strength of this correlation in the posterior cingulate predicted the amount of information subsequently recalled. This is likely to reflect a strengthening of the representation of the video's content. We argue that these representations combine both new episodic information and stored semantic knowledge (or "schemas"). We therefore suggest that posterior midline structures aid consolidation by reinstating and strengthening the associations between episodic details and more generic schematic information. This leads to the creation of coherent memory representations of lifelike, complex events that are resistant to forgetting, but somewhat inflexible and semantic-like in nature

Minocycline differentially modulates human spatial memory systems

Microglia play a critical role in many processes fundamental to learning and memory in health and are implicated in Alzheimer’s pathogenesis. Minocycline, a centrally-penetrant tetracycline antibiotic, inhibits microglial activation and enhances long-term potentiation, synaptic plasticity, neurogenesis and hippocampal-dependent spatial memory in rodents, leading to clinical trials in human neurodegenerative diseases. However, the effects of minocycline on human memory have not previously been investigated. Utilising a double-blind, randomised crossover study design, we recruited 20 healthy male participants (mean 24.6 ± 5.0 years) who were each tested in two experimental sessions: once after 3 days of Minocycline 150 mg (twice daily), and once 3 days of placebo (identical administration). During each session, all completed an fMRI task designed to tap boundary- and landmark-based navigation (thought to rely on hippocampal and striatal learning mechanisms respectively). Given the rodent literature, we hypothesised that minocycline would selectively modulate hippocampal learning. In line with this, minocycline biased use of boundary- compared to landmark-based information (t980 = 3.140, p = 0.002). However, though this marginally improved performance for boundary-based objects (t980 = 1.972, p = 0.049), it was outweighed by impaired landmark-based navigation (t980 = 6.374, p < 0.001) resulting in an overall performance decrease (t980 = 3.295, p = 0.001). Furthermore, against expectations, minocycline significantly reduced activity during memory encoding in the right caudate (t977 = 2.992, p = 0.003) and five other cortical regions, with no significant effect in the hippocampus. In summary, minocycline impaired human spatial memory performance, likely through disruption of striatal processing resulting in greater biasing towards reliance on boundary-based navigation

The importance of dry woodlands and forests in rural livelihoods and poverty alleviation in South Africa

Indigenous forests and savannas, along with plantation forests, offer numerous benefits to rural communities and society at large. Yet, the role of forests and forestry in contributing to sustainable livelihoods and poverty alleviation are widely debated. However, much of the debate pertains to lessons from the humid tropics, with little consideration of the widespread dry forests and savannas. This paper considers the role of dry forest types, including savannas, using South Africa as a case example. It concludes that a large proportion of the population makes use of forests and the resources from them. These are vital components of local livelihoods, which probably prevent people from slipping into deeper poverty. Moreover, for a measurable proportion, engagement in informal forest activities, as well as the formal forestry sector, has resulted in them being able to move out of poverty. Additionally, the generally dry nature of forests in South Africa, coupled with the high unemployment rate, limit the extent of alternative locally based livelihood options, thereby magnifying the contributions from forests and forest products. The depressing effects of widespread HIV/AIDS on labour availability, economic activities and livelihoods has exacerbated peoples' dependence on forest products

Recovery practice in community mental health teams: national survey

Background There is consensus about the importance of ‘recovery’ in mental health services, but the link between recovery orientation of mental health teams and personal recovery of individuals has been underresearched. Aims To investigate differences in team leader, clinician and service user perspectives of recovery orientation of community adult mental health teams in England. Method In six English mental health National Health Service (NHS) trusts, randomly chosen community adult mental health teams were surveyed. A random sample of ten patients, one team leader and a convenience sample of five clinicians were surveyed from each team. All respondents rated the recovery orientation of their team using parallel versions of the Recovery Self Assessment (RSA). In addition, service users also rated their own personal recovery using the Questionnaire about Processes of Recovery (QPR). Results Team leaders (n = 22) rated recovery orientation higher than clinicians (n = 109) or patients (n = 120) (Wald(2) = 7.0, P = 0.03), and both NHS trust and team type influenced RSA ratings. Patient-rated recovery orientation was a predictor of personal recovery (b = 0.58, 95% CI 0.31–0.85, P50.001). Team leaders and clinicians with experience of mental illness (39%) or supporting a family member or friend with mental illness (76%) did not differ in their RSA ratings from other team leaders or clinicians. Conclusions Compared with team leaders, frontline clinicians and service users have less positive views on recovery orientation. Increasing recovery orientation may support personal recovery

Human hippocampal theta power indicates movement onset and distance travelled

Theta frequency oscillations in the 6- to 10-Hz range dominate the rodent hippocampal local field potential during translational movement, suggesting that theta encodes self-motion. Increases in theta power have also been identified in the human hippocampus during both real and virtual movement but appear as transient bursts in distinct high- and low-frequency bands, and it is not yet clear how these bursts relate to the sustained oscillation observed in rodents. Here, we examine depth electrode recordings from the temporal lobe of 13 presurgical epilepsy patients performing a selfpaced spatial memory task in a virtual environment. In contrast to previous studies, we focus on movement-onset periods that incorporate both initial acceleration and an immediately preceding stationary interval associated with prominent theta oscillations in the rodent hippocampal formation. We demonstrate that movementonset periods are associated with a significant increase in both low (2–5 Hz)- and high (6–9 Hz)-frequency theta power in the human hippocampus. Similar increases in low- and high-frequency theta power are seen across lateral temporal lobe recording sites and persist throughout the remainder of movement in both regions. In addition, we show that movement-related theta power is greater both before and during longer paths, directly implicating human hippocampal theta in the encoding of translational movement. These findings strengthen the connection between studies of theta-band activity in rodents and humans and offer additional insight into the neural mechanisms of spatial navigation

CAG expansion affects the expression of mutant huntingtin in the Huntington's disease brain

AbstractA trinucleotide repeat (CAG) expansion in the huntingtin gene causes Huntington's disease (HD). In brain tissue from HD heterozygotes with adult onset and more clinically severe juvenile onset, where the largest expansions occur, a mutant protein of equivalent intensity to wild-type huntingtin was detected in cortical synaptosomes, indicating that a mutant species is synthesized and transported with the normal protein to nerve endings. The increased size of mutant huntingtin relative to the wild type was highly correlated with CAG repeat expansion, thereby linking an altered electrophoretic mobility of the mutant protein to its abnormal function. Mutant huntingtin appeared in gray and white matter with no difference in expression in affected regions. The mutant protein was broader than the wild type and in 6 of 11 juvenile cases resolved as a complex of bands, consistent with evidence at the DNA level for somatic mosaicism. Thus, HD pathogenesis results from a gain of function by an aberrant protein that is widely expressed in brain and is harmful only to some neurons