Age-related alterations in human neocortical plasticity.

Age-related changes in neuroplasticity may be central to the cognitive decline associated with healthy ageing. Modulated Long-Term Potentiation (LTP) and Long-Term Depression (LTD) have been repeatedly demonstrated in aged rodents, however the translation to human research has been limited by a scarcity of non-invasive methods for doing so. We have previously demonstrated that, following a block of high frequency presentations of a visual stimulus (referred to as a "visual tetanus"), there is a LTP-like enhancement of the N1b component of the visually evoked potential (VEP) to subsequent low frequency presentations of the same stimulus. The aims of the current study were, firstly, to use this electroencephalography (EEG) paradigm to assess age group differences in neocortical plasticity in humans, and secondly, to expand on the visual LTP paradigm by examining plasticity in another component of the VEP; the P2a. While a young participant group (N=29, age range=19-35) demonstrated the expected LTP-like enhancement of the N1b immediately following the visual tetanus, an older participant group (N=19, age range=68-91) did not. However, both age groups demonstrated a positive shift of the P2a component after repeated presentations of low frequency baseline blocks, which is hypothesized to be an LTD-like shift in the VEP. These results support the rodent literature indicating an age-related shift in threshold for LTP, but a relative preservation of the threshold for LTD. This study not only provides valuable insight into healthy age-related alterations in neocortical plasticity, but is also the first to identify an LTD-like modulation of the VEP in humans.

No change in progenitor cell proliferation in the hippocampus in Huntington's disease.

Increases in cell proliferation in the hippocampus have been robustly demonstrated in animal models of neurodegenerative diseases like Huntington's disease (HD). However, in the subventricular zone, animal models of HD have demonstrated no change in cell proliferation compared to wild types, while in humans there is a distinct increase in cell proliferation in HD cases. Interestingly, there have been no reports on cell proliferation in the human subgranular zone (SGZ) of the hippocampus in HD, despite numerous transgenic mouse models of HD showing decreased proliferation in the SGZ. Furthermore, HD can be divided into those with mainly mood and mainly motor symptomatology. We hypothesized that HD cases with mainly mood symptomatology would show a greater change in hippocampal proliferation, which has previously been implicated in mood disorders such as depression. Therefore, in the current study we examined and compared proliferation in the SGZ in normal vs. HD, HD mood, and HD motor affected cases. However, our results revealed no significant differences in SGZ proliferation between normal and HD cases, and no differences when divided into groups based on mood and motor symptomatology. Our results were confirmed using a range of cell-cycle protein markers and, overall, were comparable with previous studies of the human hippocampus, where very little proliferation was detected in the adult SGZ. These results demonstrate that in humans the SGZ is far less proliferative than the SVZ, and suggests that hippocampal plasticity in humans does not primarily involve cell proliferation.

Prosopamnesia: a selective impairment in face learning.

The structures required for new learning, and those required for the representation of what has been learned, are believed to be distinct. This counterintuitive division of labour when considered alongside the localised nature of knowledge representation for at least some stimulus domains, implies that circumscribed new learning impairments should occasionally be found as a result of disconnection between learning mechanisms and domain-specific representations. We describe the most narrowly circumscribed new learning deficit so far reported, consisting of a selective new learning impairment for faces, which we term "prosopamnesia." Logically, a diagnosis of prosopamnesia requires preserved face perception, preserved memory for material other than faces (including visual material), and preserved recognition of faces known premorbidly. We describe a patient who meets these criteria, thus supporting the division of labour between neural systems for learning and neural systems for knowledge representation, as well as providing further support for segregated face representation in cortex.

Effects of focal brain lesions on visual problem-solving.

In this study, the relative contributions of different brain regions to visual problem-solving were explored using a new test of divergent thinking. Seventy-three patients with focal brain lesions and 20 normal control subjects performed a set of matchstick problems, similar to those described by Guilford [15] as a measure of adaptive flexibility. For each problem, subjects were to demonstrate as many ways as possible of removing a particular number of sticks from a two-dimensional geometric design to achieve a specified resultant shape. Patients with left temporal-occipital, right temporal-occipital, or left frontal lesions displayed no significant difficulty. Evidence of general deficiencies in the ability to manipulate this visual material was seen in patients with parietal and/or central-area lesions (right worse than left). In contrast, patients with right frontal-lobe damage demonstrated a selective impairment in the ability to shift strategy. The results confirm the importance of the right suprasylvian region in the ability to process and act on visual information. They also provide evidence of the specific role played by the right frontal lobe, and particularly the ventral region, in permitting a flexible approach to visual problem-solving.

The semantic memory impairment of Alzheimer's disease: category-specific?

We addressed the question of whether Alzheimer's Disease (AD) causes a selective impairment for knowledge of living things. Although we replicated a previous finding that AD subjects name pictures of living things less accurately than pictures of nonliving things, we also failed to observe this selective impairment when we used two new stimulus sets, which more tightly controlled the overall naming difficulty of the living and nonliving items. We conclude that, whereas some individuals may have bona fide selective impairments in semantic memory as a result of herpes simplex encephalitis or head injury, AD does not generally give rise to selective impairments in knowledge of living things.

A category-specific naming impairment after temporal lobectomy.

Unilateral temporal lobectomy patients and normal control subjects were tested in a speeded naming task with pictures of living and nonliving things that were equated for name frequency, familiarity, and visual complexity. Although right temporal lobectomy patients and normal subjects performed equally well with the living relative to nonliving things, left temporal lobectomy patients were disproportionately impaired at naming nonliving things. This result has several implications: First, it supports the existence of category-specific naming impairments. In particular, it undermines the proposal that living-nonliving dissociations are artifactual, resulting from the greater difficulty of living things. Second, it demonstrates an asymmetry in the neural representation of nonliving things, in favor of the left hemisphere. Third, it casts doubt on the hypothesis that the anterior temporal cortices are convergence zones that are particularly necessary for the naming of living things.

Preservation of categorical knowledge in Alzheimer's disease: a computational account.

The distinction between knowledge of specific exemplars and knowledge of their general categories is central to much theorising on the nature of semantic memory. The dissociation between exemplar and category knowledge observed in Alzheimer's Disease (AD) would appear to support this distinction, and to suggest that different neural systems are involved in the representation of exemplar and category knowledge. We review the evidence for preserved category knowledge in the semantic memory impairment of AD, and propose an alternative interpretation, according to which category and exemplar knowledge are both represented in the same distributed neural substrate. The relative preservation of category knowledge is a consequence of the greater frequency, and hence greater robustness, of the representation of attributes shared by all or most members of a category, compared to exemplar-unique attributes. We test and confirm the computational adequacy of this hypothesis in two computer simulations.

The generation of visual images: a review of neuropsychological research and theory.

Since the advent of the view that mental imagery is a subdividable process, claims have been made that the generation of images is the domain of the left posterior hemisphere. This article examines theory and data about the neuropsychology of image generation by focusing on the main contributors to the debate. An attempt is made to make the theory and beliefs associated with each of the key figures explicit, because these have influenced the structure of research and the development of new theories. Support is found for the involvement of the left hemisphere, although many researchers claim that the posterior regions of both hemispheres contribute to image generation but that they do so in different ways. The nature of this difference remains the subject of ongoing research.