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Antemortem behavioural and anatomic abnormalities have largely been associated with right hemisphere disease in behavioural-variant frontotemporal dementia, but post-mortem neuropathological examination of bilateral hemispheres remains to be defined. Here we measured the severity of post-mortem pathology in both grey and white matter using a validated digital image analysis method in four cortical regions sampled from each hemisphere in 26 patients with behavioural-variant frontotemporal dementia, including those with frontotemporal degeneration (i.e. tau = 9, TDP-43 = 14, or FUS = 1 proteinopathy) or Alzheimer's pathology (n = 2). We calculated an asymmetry index based on the difference in measured pathology from each left-right sample pair. Analysis of the absolute value of the asymmetry index (i.e. degree of asymmetry independent of direction) revealed asymmetric pathology for both grey and white matter in all four regions sampled in frontototemporal degeneration patients with tau or TDP-43 pathology (P ≤ 0.01). Direct interhemispheric comparisons of regional pathology measurements within-subjects in the combined tauopathy and TDP-43 proteinopathy group found higher pathology in the right orbitofrontal grey matter compared to the left (P < 0.01) and increased pathology in ventrolateral temporal lobe grey matter of the left hemisphere compared to the right (P < 0.02). Preliminary group-wise comparisons between tauopathy and TDP-43 proteinopathy groups found differences in patterns of interhemispheric burden of grey and white matter regional pathology, with greater relative white matter pathology in tauopathies. To test the association of pathology measurement with ante-mortem observations, we performed exploratory analyses in the subset of patients with imaging data (n = 15) and found a direct association for increasing pathologic burden with decreasing cortical thickness in frontotemporal regions on ante-mortem imaging in tauopathy (P = 0.001) and a trend for TDP-43 proteinopathy (P = 0.06). Exploratory clinicopathological correlations demonstrated an association of socially-inappropriate behaviours with asymmetric right orbitofrontal grey matter pathology, and reduced semantically-guided category naming fluency was associated asymmetric white matter pathology in the left ventrolateral temporal region. We conclude that pathologic disease burden is distributed asymmetrically in behavioural-variant frontotemporal dementia, although not universally in the right hemisphere, and this asymmetry contributes to the clinical heterogeneity of the disorder. The basis for this asymmetric profile is enigmatic but may reflect distinct species or strains of tau and TDP-43 pathologies with propensities to spread by distinct cell- and region-specific mechanisms. Patterns of region-specific pathology in the right hemisphere as well as the left hemisphere may play a role in antemortem clinical observations, and these observations may contribute to antemortem identification of molecular pathology in frontotemporal degeneration., (© The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

We investigated the relationship between stimulus similarity for a set of parameterized shapes and the spatial scale of neural representation within subregions of the lateral occipital complex (LOC) using a carryover functional magnetic resonance imaging design. In ventral but not lateral LOC, a linear recovery from adaptation proportional to shape dissimilarity was seen. In contrast, a strong correspondence of the distributed neural pattern and stimulus similarity was observed in lateral LOC but not ventral LOC. Further, ventral LOC voxels were found to be broadly tuned and represent all aspects of stimulus similarity, whereas lateral LOC voxels were narrowly tuned and preferentially represented the shape of small features rather than their orientation within the shape. The results, indicating a coarse spatial coding of shape features in lateral LOC and a more focused coding of the entire shape space within ventral LOC, may be related to hierarchical models of object processing.

The Philadelphia Face Perception Battery (PFPB) tests four aspects of face perception: discrimination of facial similarity, attractiveness, gender, and age. Calibration with 116 neurologically intact subjects yielded average performance of approximately 90%. Across subjects, there was a low correlation (<0.22) in performance between the tests (with the exception of the attractiveness and age discrimination tests) suggesting that the tests measure independent aspects of face perception. There were modest effects of subject demographic factors upon performance, and test-retest reliability scores (between 0.37 and 0.75) were comparable to other neuropsychological batteries. Modification of the stimuli to obscure internal facial features lowered performance on the age, gender, and attractiveness discrimination tests between 2 and 4 standard deviations. The clinical sensitivity of the battery was demonstrated by testing a patient with acquired prosopagnosia. She showed performance impairments of between 2 and 4 standard deviations on all sub-tests. The PFPB is freely available for non-commercial use.

Over the last century, several dozen case reports have presented 'topographically disoriented' patients who, in some cases, appear to have selectively lost their ability to find their way within large-scale, locomotor environments. A review is offered here that has as its aim the creation of a taxonomy that accurately reflects the behavioural impairments and neuroanatomical findings of this literature. This effort is guided by an appreciation of the models of normative way-finding offered by environmental psychology and recent neuroscience research. It is proposed that several varieties of topographical disorientation exist, resulting from damage to distinct neuroanatomical areas. The particular pattern of impairments that patients evidence is argued to be consonant with the known functions of these cortical regions and with recent neuroimaging results. The conflicting claims of previous reviews of this area are also considered and addressed.

The hippocampus has been proposed as the site of neural representation of large-scale environmental space, based upon the identification of place cells (neurons with receptive fields for current position in the environment) within the rat hippocampus and the demonstration that hippocampal lesions impair place learning in the rat. The inability to identify place cells within the monkey hippocampus and the observation that unilateral hippocampal lesions do not selectively impair topographic behavior in humans suggest that alternate regions may subserve this function in man. To examine the contribution of the hippocampus and adjacent medial-temporal lobe structures to topographic learning in the human, a 'virtual' maze was used as a task environment during functional magnetic resonance imaging studies. During the learning and recall of topographic information, medial-temporal activity was confined to the para- hippocampal gyri. This activity accords well with the lesion site known to produce topographical disorientation in humans. Activity was also observed in cortical areas known to project to the parahippocampus and previously proposed to contribute to a network subserving spatially guided behavior.