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  • The forgotten APOE allele: A review of the evidence and suggested mechanisms for the protective effect of APOE e2

    24 October 2018

    Ongoing efforts to improve survival, and enhance quality of life have led biomedical research to focus on disease and the mechanisms that increase risk for disease. The other side of that coin may be as important, i.e. examining the protective factors that allow some individuals to enjoy long, healthy lives. One of the best examples of a gene that positively influences cognitive health is the apolipoprotein (APOE) e2 allele. The APOE e4 allele is a well-established risk factor for Alzheimer's disease (AD) and has thus dominated the APOE literature, with the putative protective role of e2 receiving little attention. This review describes the effects of APOE e2 on the structure and function of the brain. With a focus on neurodegeneration, we discuss evidence for APOE e2's protective effects, explore some key mechanisms through which this protection may be conferred, and address a few inconsistencies in the literature. Understanding the mechanisms that underlie the association between APOE e2, cognition and longevity may provide new targets for research on promoting life-long health. © 2013 Elsevier Ltd.

  • 12. Prefrontal cortical activation during word-associative, face-associative, and word-face-associative encoding

    24 October 2018

    We report a fMRI study of associative encoding. Subjects studied blocks of word pairs, face pairs, and word-face pairs under two encoding instructions, which either involved judgments about the individual items comprising the pairs or required subjects to associate the items. Comparisons between these two encoding conditions revealed the following. First, consistent with HERA, for both face pairs and word pairs there was a large overlapping region of activation which was left lateralized, with little evidence of material specificity. Second, this activation involved principally Brodmann areas 8 and 9, a region more dorsal than those previously reported. Third, the activation pattern for encoding associations between different kinds of items, word-face pairs, was different from the first pattern and involved bilateral anterior portions of area 47. © 2001 Academic Press.

  • The neural basis of flashback formation: The impact of viewing trauma

    24 October 2018

    Background Psychological traumatic events, such as war or road traffic accidents, are widespread. A small but significant proportion of survivors develop post-traumatic stress disorder (PTSD). Distressing, sensory-based involuntary memories of trauma (henceforth 'flashbacks') are the hallmark symptom of PTSD. Understanding the development of flashbacks may aid their prevention. This work is the first to combine the trauma film paradigm (as an experimental analogue for flashback development) with neuroimaging to investigate the neural basis of flashback aetiology. We investigated the hypothesis that involuntary recall of trauma (flashback) is determined during the original event encoding. Method A total of 22 healthy volunteers viewed a traumatic film whilst undergoing functional magnetic resonance imaging (fMRI). They kept a 1-week diary to record flashbacks to specific film scenes. Using a novel prospective fMRI design, we compared brain activation for those film scenes that subsequently induced flashbacks with both non-traumatic control scenes and scenes with traumatic content that did not elicit flashbacks ('potentials'). Results Encoding of scenes that later caused flashbacks was associated with widespread increases in activation, including in the amygdala, striatum, rostral anterior cingulate cortex, thalamus and ventral occipital cortex. The left inferior frontal gyrus and bilateral middle temporal gyrus also exhibited increased activation but only relative to 'potentials'. Thus, these latter regions appeared to distinguish between traumatic content that subsequently flashed back and comparable content that did not. Conclusions Results provide the first prospective evidence that the brain behaves differently whilst experiencing emotional events that will subsequently become involuntary memories-flashbacks. Understanding the neural basis of analogue flashback memory formation may aid the development of treatment interventions for this PTSD feature. © 2012 Cambridge University Press.

  • Corpus callosum damage in heavy marijuana use: preliminary evidence from diffusion tensor tractography and tract-based spatial statistics.

    24 October 2018

    Heavy marijuana use has well established long term consequences for cognition and mental health, but the effect on brain structure is less well understood. We used an MRI technique that is sensitive to the structural integrity of brain tissue combined with a white matter mapping tractography technique to investigate structural changes in the corpus callosum (CC). Diffusion tensor imaging (DTI) was obtained in eleven heavy marijuana users who started using marijuana in early adolescence and eleven age matched controls. Mean diffusivity (MD) and fractional anisotropy (FA) (which measure structural integrity and tract coherence, respectively) were analysed within the corpus callosum which was spatially defined using tractography and tract-based spatial statistics (TBSS). MD was significantly increased in marijuana users relative to controls in the region of the CC where white matter passes between the prefrontal lobes. This observation suggests impaired structural integrity affecting the fibre tracts of the CC and is in keeping with previous reports of altered and diversified activation patterns in marijuana users. There was a trend towards a positive correlation between MD and length of use suggesting the possibility of a cumulative effect of marijuana over time and that a younger age at onset of use may predispose individuals to structural white matter damage. Structural abnormalities revealed in the CC may underlie cognitive and behavioural consequences of long term heavy marijuana use.