Longitudinal neuroanatomical and cognitive progression of posterior cortical atrophy.

Posterior cortical atrophy is a clinico-radiological syndrome characterized by progressive decline in visual processing and atrophy of posterior brain regions. With the majority of cases attributable to Alzheimer's disease and recent evidence for genetic risk factors specifically related to posterior cortical atrophy, the syndrome can provide important insights into selective vulnerability and phenotypic diversity. The present study describes the first major longitudinal investigation of posterior cortical atrophy disease progression. Three hundred and sixty-one individuals (117 posterior cortical atrophy, 106 typical Alzheimer's disease, 138 controls) fulfilling consensus criteria for posterior cortical atrophy-pure and typical Alzheimer's disease were recruited from three centres in the UK, Spain and USA. Participants underwent up to six annual assessments involving MRI scans and neuropsychological testing. We constructed longitudinal trajectories of regional brain volumes within posterior cortical atrophy and typical Alzheimer's disease using differential equation models. We compared and contrasted the order in which regional brain volumes become abnormal within posterior cortical atrophy and typical Alzheimer's disease using event-based models. We also examined trajectories of cognitive decline and the order in which different cognitive tests show abnormality using the same models. Temporally aligned trajectories for eight regions of interest revealed distinct (P < 0.002) patterns of progression in posterior cortical atrophy and typical Alzheimer's disease. Patients with posterior cortical atrophy showed early occipital and parietal atrophy, with subsequent higher rates of temporal atrophy and ventricular expansion leading to tissue loss of comparable extent later. Hippocampal, entorhinal and frontal regions underwent a lower rate of change and never approached the extent of posterior cortical involvement. Patients with typical Alzheimer's disease showed early hippocampal atrophy, with subsequent higher rates of temporal atrophy and ventricular expansion. Cognitive models showed tests sensitive to visuospatial dysfunction declined earlier in posterior cortical atrophy than typical Alzheimer's disease whilst tests sensitive to working memory impairment declined earlier in typical Alzheimer's disease than posterior cortical atrophy. These findings indicate that posterior cortical atrophy and typical Alzheimer's disease have distinct sites of onset and different profiles of spatial and temporal progression. The ordering of disease events both motivates investigation of biological factors underpinning phenotypic heterogeneity, and informs the selection of measures for clinical trials in posterior cortical atrophy.

Verbal adynamia in parkinsonian syndromes: behavioral correlates and neuroanatomical substrate.

Verbal adynamia (impaired language generation, as during conversation) has not been assessed systematically in parkinsonian disorders. We addressed this in patients with Parkinson's dementia, progressive supranuclear palsy and corticobasal degeneration. All disease groups showed impaired verbal fluency and sentence generation versus healthy age-matched controls, after adjusting for general linguistic and executive factors. Dopaminergic stimulation in the Parkinson's group selectively improved verbal generation versus other cognitive functions. Voxel-based morphometry identified left inferior frontal and posterior superior temporal cortical correlates of verbal generation performance. Verbal adynamia warrants further evaluation as an index of language network dysfunction and dopaminergic state in parkinsonian disorders.

A double-blind placebo-controlled cross-over clinical trial of DONepezil In Posterior cortical atrophy due to underlying Alzheimer's Disease: DONIPAD study.

BACKGROUND: The study investigated whether donepezil exerts symptomatic benefit in patients with posterior cortical atrophy (PCA), an atypical variant of Alzheimer's disease. METHODS: A single-centre, double-blind, placebo-controlled, cross-over clinical trial was performed to assess the efficacy of donepezil in patients with PCA. Each patient received either donepezil (5 mg once daily in the first 6 weeks and 10 mg once daily in the second 6 weeks) or placebo for 12 weeks. After a 2-week washout period, each patient received the other treatment arm during the following 12 weeks followed by another 2-week washout period. The primary outcome was the Mini-Mental State Examination (MMSE) at 12 weeks. Secondary outcome measures were five neuropsychological tests reflecting parieto-occipital function. Intention-to-treat analysis was used. For each outcome measure, carry-over effects were first assessed. If present, then analysis was restricted to the first 12-week period. Otherwise, the standard approach to the analysis of a 2 × 2 cross-over trial was used. RESULTS: Eighteen patients (13 females) were recruited (mean age 61.6 years). There was a protocol violation in one patient, who subsequently withdrew from the study due to gastrointestinal side effects. There was statistically significant (p < 0.05) evidence of a carry-over effect on MMSE. Therefore, the analysis of treatment effect on MMSE was restricted to the first 12-week period. Treatment effect at 6 weeks was statistically significant (difference = 2.5 in favour of donepezil, 95% CI 0.1 to 5.0, p < 0.05). Treatment effect at 12 weeks was close, but not statistically significant (difference = 2.0 in favour of donepezil, 95% CI -0.1 to 4.5, p > 0.05). There were no statistically significant treatment effects on any of the five neuropsychological tests, except for digit span at 12 weeks (higher by 0.5 digits in favour of placebo, 95% CI 0.1 to 0.9). Gastrointestinal side effects occurred most frequently, affecting 13/18 subjects (72%), and were the cause of study discontinuation in one subject. Nightmares and vivid dreams occurred in 8/18 subjects (44%), and were statistically more frequent during treatment with donepezil. CONCLUSIONS: In this small study, there was no statistically significant treatment effect of donepezil on the primary outcome measure (MMSE score at 12 weeks) in PCA patients, who appear to be particularly susceptible to the development of nightmares and vivid dreams when treated. TRIAL REGISTRATION: Trial registration: Current Controlled Trials ISRCTN22636071 . Retrospectively registered 19 May 2010.

Agnosia for bird calls.

The cognitive organisation of nonverbal auditory knowledge remains poorly defined. Deficits of environmental sound as well as word and visual object knowledge are well-recognised in semantic dementia. However, it is unclear how auditory cognition breaks down in this disorder and how this relates to deficits in other knowledge modalities. We had the opportunity to study a patient with a typical syndrome of semantic dementia who had extensive premorbid knowledge of birds, allowing us to assess the impact of the disease on the processing of auditory in relation to visual and verbal attributes of this specific knowledge category. We designed a novel neuropsychological test to probe knowledge of particular avian characteristics (size, behaviour [migratory or nonmigratory], habitat [whether or not primarily water-dwelling]) in the nonverbal auditory, visual and verbal modalities, based on a uniform two-alternative-forced-choice procedure. The patient's performance was compared to healthy older individuals of similar birding experience. We further compared his performance on this test of bird knowledge with his knowledge of familiar human voices and faces. Relative to healthy birder controls, the patient showed marked deficits of bird call and bird name knowledge but relatively preserved knowledge of avian visual attributes and retained knowledge of human voices and faces. In both the auditory and visual modalities, his knowledge of the avian characteristics of size and behaviour was intact whereas his knowledge of the associated characteristic of habitat was deficient. This case provides further evidence that nonverbal auditory knowledge has a fractionated organisation that can be differentially targeted in semantic dementia.

The Language Profile of Behavioral Variant Frontotemporal Dementia.

BACKGROUND: The language profile of behavioral variant frontotemporal dementia (bvFTD) remains to be fully defined. OBJECTIVE: We aimed to quantify the extent of language deficits in this patient group. METHODS: We assessed a cohort of patients with bvFTD (n = 24) in relation to patients with semantic variant primary progressive aphasia (svPPA; n = 14), nonfluent variant primary progressive aphasia (nfvPPA; n = 18), and healthy age-matched individuals (n = 24) cross-sectionally and longitudinally using a comprehensive battery of language and general neuropsychological tests. Neuroanatomical associations of language performance were assessed using voxel-based morphometry of patients' brain magnetic resonance images. RESULTS: Relative to healthy controls, and after accounting for nonverbal executive performance, patients with bvFTD showed deficits of noun and verb naming and single word comprehension, diminished spontaneous propositional speech, and deterioration in naming performance over time. Within the bvFTD group, patients with MAPT mutations had more severe impairments of noun naming and single word comprehension than patients with C9orf72 mutations. Overall the bvFTD group had less severe language deficits than patients with PPA, but showed a language profile that was qualitatively similar to svPPA. Neuroanatomical correlates of naming and word comprehension performance in bvFTD were identified predominantly in inferior frontal and antero-inferior temporal cortices within the dominant hemispheric language network. CONCLUSIONS: bvFTD is associated with a language profile including verbal semantic impairment that warrants further evaluation as a novel biomarker.

Past, present, and prospects: Reflections 40 years on from the selective impairment of semantic memory (Warrington, 1975).

We summarize the main findings and conclusions of Warrington's (1975) paper, The Selective Impairment of Semantic memory, a neuropsychological paper that described three cases with degenerative neurological conditions [Warrington, E. K. (1975). The selective impairment of semantic memory. The Quarterly Journal of Experimental Psychology, 27, 635-657]. We consider the developments that have followed from its publication and give a selective overview of the field in 2014. The initial impact of the paper was on neuropsychological investigations of semantic loss followed some 14 years later by the identification of Semantic Dementia (the condition shown by the original cases) as a distinctive form of degenerative disease with unique clinical and pathological characteristics. We discuss the distinction between disorders of semantic storage and refractory semantic access, the evidence for category- and modality-specific impairments of semantics, and the light that has been shed on the structure and organization of semantic memory. Finally we consider the relationship between semantic memory and the skills of reading and writing, phonological processing, and autobiographical memory.

Prominent effects and neural correlates of visual crowding in a neurodegenerative disease population.

Crowding is a breakdown in the ability to identify objects in clutter, and is a major constraint on object recognition. Crowding particularly impairs object perception in peripheral, amblyopic and possibly developing vision. Here we argue that crowding is also a critical factor limiting object perception in central vision of individuals with neurodegeneration of the occipital cortices. In the current study, individuals with posterior cortical atrophy (n=26), typical Alzheimer's disease (n=17) and healthy control subjects (n=14) completed centrally-presented tests of letter identification under six different flanking conditions (unflanked, and with letter, shape, number, same polarity and reverse polarity flankers) with two different target-flanker spacings (condensed, spaced). Patients with posterior cortical atrophy were significantly less accurate and slower to identify targets in the condensed than spaced condition even when the target letters were surrounded by flankers of a different category. Importantly, this spacing effect was observed for same, but not reverse, polarity flankers. The difference in accuracy between spaced and condensed stimuli was significantly associated with lower grey matter volume in the right collateral sulcus, in a region lying between the fusiform and lingual gyri. Detailed error analysis also revealed that similarity between the error response and the averaged target and flanker stimuli (but not individual target or flanker stimuli) was a significant predictor of error rate, more consistent with averaging than substitution accounts of crowding. Our findings suggest that crowding in posterior cortical atrophy can be regarded as a pre-attentive process that uses averaging to regularize the pathologically noisy representation of letter feature position in central vision. These results also help to clarify the cortical localization of feature integration components of crowding. More broadly, we suggest that posterior cortical atrophy provides a neurodegenerative disease model for exploring the basis of crowding. These data have significant implications for patients with, or who will go on to develop, dementia-related visual impairment, in whom acquired excessive crowding likely contributes to deficits in word, object, face and scene perception.

Scene perception in posterior cortical atrophy: categorization, description and fixation patterns.

Partial or complete Balint's syndrome is a core feature of the clinico-radiological syndrome of posterior cortical atrophy (PCA), in which individuals experience a progressive deterioration of cortical vision. Although multi-object arrays are frequently used to detect simultanagnosia in the clinical assessment and diagnosis of PCA, to date there have been no group studies of scene perception in patients with the syndrome. The current study involved three linked experiments conducted in PCA patients and healthy controls. Experiment 1 evaluated the accuracy and latency of complex scene perception relative to individual faces and objects (color and grayscale) using a categorization paradigm. PCA patients were both less accurate (faces < scenes < objects) and slower (scenes < objects < faces) than controls on all categories, with performance strongly associated with their level of basic visual processing impairment; patients also showed a small advantage for color over grayscale stimuli. Experiment 2 involved free description of real world scenes. PCA patients generated fewer features and more misperceptions than controls, though perceptual errors were always consistent with the patient's global understanding of the scene (whether correct or not). Experiment 3 used eye tracking measures to compare patient and control eye movements over initial and subsequent fixations of scenes. Patients' fixation patterns were significantly different to those of young and age-matched controls, with comparable group differences for both initial and subsequent fixations. Overall, these findings describe the variability in everyday scene perception exhibited by individuals with PCA, and indicate the importance of exposure duration in the perception of complex scenes.

Agnosia for accents in primary progressive aphasia.

As an example of complex auditory signal processing, the analysis of accented speech is potentially vulnerable in the progressive aphasias. However, the brain basis of accent processing and the effects of neurodegenerative disease on this processing are not well understood. Here we undertook a detailed neuropsychological study of a patient, AA with progressive nonfluent aphasia, in whom agnosia for accents was a prominent clinical feature. We designed a battery to assess AA's ability to process accents in relation to other complex auditory signals. AA's performance was compared with a cohort of 12 healthy age and gender matched control participants and with a second patient, PA, who had semantic dementia with phonagnosia and prosopagnosia but no reported difficulties with accent processing. Relative to healthy controls, the patients showed distinct profiles of accent agnosia. AA showed markedly impaired ability to distinguish change in an individual's accent despite being able to discriminate phonemes and voices (apperceptive accent agnosia); and in addition, a severe deficit of accent identification. In contrast, PA was able to perceive changes in accents, phonemes and voices normally, but showed a relatively mild deficit of accent identification (associative accent agnosia). Both patients showed deficits of voice and environmental sound identification, however PA showed an additional deficit of face identification whereas AA was able to identify (though not name) faces normally. These profiles suggest that AA has conjoint (or interacting) deficits involving both apperceptive and semantic processing of accents, while PA has a primary semantic (associative) deficit affecting accents along with other kinds of auditory objects and extending beyond the auditory modality. Brain MRI revealed left peri-Sylvian atrophy in case AA and relatively focal asymmetric (predominantly right sided) temporal lobe atrophy in case PA. These cases provide further evidence for the fractionation of brain mechanisms for complex sound analysis, and for the stratification of progressive aphasia syndromes according to the signature of nonverbal auditory deficits they produce.

Intact reading in patients with profound early visual dysfunction.

Despite substantial neuroscientific evidence for a region of visual cortex dedicated to the processing of written words, many studies continue to reject explanations of letter-by-letter (LBL) reading in terms of impaired word form representations or parallel letter processing in favour of more general deficits of visual function. In the current paper, we demonstrate that whilst LBL reading is often associated with general visual deficits, these deficits are not necessarily sufficient to cause reading impairment and have led to accounts of LBL reading which are based largely on evidence of association rather than causation. We describe two patients with posterior cortical atrophy (PCA) who exhibit remarkably preserved whole word and letter reading despite profound visual dysfunction. Relative to controls, both patients demonstrated impaired performance on tests of early visual, visuoperceptual and visuospatial processing; visual acuity was the only skill preserved in both individuals. By contrast, both patients were able to read aloud words with perfect to near-perfect accuracy. Reading performance was also rapid with no overall significant difference in response latencies relative to age- and education-matched controls. Furthermore, the patients violated a key prediction of general visual accounts of LBL reading - that pre-lexical impairments should result in prominent word length effects; in the two reported patients, evidence for abnormal word length effects was equivocal or absent, and certainly an order of magnitude different to that reported for LBL readers. We argue that general visual accounts cannot explain the pattern of reading data reported, and attribute the preserved reading performance to preserved direct access to intact word form representations and/or parallel letter processing mechanisms. The current data emphasise the need for much clearer evidence of causality when attempting to draw connections between specific aspects of visual processing and different types of acquired peripheral dyslexia.

Frontotemporal dementia with the C9ORF72 hexanucleotide repeat expansion: clinical, neuroanatomical and neuropathological features.

An expanded hexanucleotide repeat in the C9ORF72 gene has recently been identified as a major cause of familial frontotemporal lobar degeneration and motor neuron disease, including cases previously identified as linked to chromosome 9. Here we present a detailed retrospective clinical, neuroimaging and histopathological analysis of a C9ORF72 mutation case series in relation to other forms of genetically determined frontotemporal lobar degeneration ascertained at a specialist centre. Eighteen probands (19 cases in total) were identified, representing 35% of frontotemporal lobar degeneration cases with identified mutations, 36% of cases with clinical evidence of motor neuron disease and 7% of the entire cohort. Thirty-three per cent of these C9ORF72 cases had no identified relevant family history. Families showed wide variation in clinical onset (43-68 years) and duration (1.7-22 years). The most common presenting syndrome (comprising a half of cases) was behavioural variant frontotemporal dementia, however, there was substantial clinical heterogeneity across the C9ORF72 mutation cohort. Sixty per cent of cases developed clinical features consistent with motor neuron disease during the period of follow-up. Anxiety and agitation and memory impairment were prominent features (between a half to two-thirds of cases), and dominant parietal dysfunction was also frequent. Affected individuals showed variable magnetic resonance imaging findings; however, relative to healthy controls, the group as a whole showed extensive thinning of frontal, temporal and parietal cortices, subcortical grey matter atrophy including thalamus and cerebellum and involvement of long intrahemispheric, commissural and corticospinal tracts. The neuroimaging profile of the C9ORF72 expansion was significantly more symmetrical than progranulin mutations with significantly less temporal lobe involvement than microtubule-associated protein tau mutations. Neuropathological examination in six cases with C9ORF72 mutation from the frontotemporal lobar degeneration series identified histomorphological features consistent with either type A or B TAR DNA-binding protein-43 deposition; however, p62-positive (in excess of TAR DNA-binding protein-43 positive) neuronal cytoplasmic inclusions in hippocampus and cerebellum were a consistent feature of these cases, in contrast to the similar frequency of p62 and TAR DNA-binding protein-43 deposition in 53 control cases with frontotemporal lobar degeneration-TAR DNA-binding protein. These findings corroborate the clinical importance of the C9ORF72 mutation in frontotemporal lobar degeneration, delineate phenotypic and neuropathological features that could help to guide genetic testing, and suggest hypotheses for elucidating the neurobiology of a culprit subcortical network.

Global gray matter changes in posterior cortical atrophy: a serial imaging study.

BACKGROUND: Posterior cortical atrophy (PCA) is a neurodegenerative condition predominantly associated with Alzheimer's disease (AD) pathology. Cross-sectional imaging studies have shown different atrophy patterns in PCA patients compared with typical amnestic Alzheimer's disease (tAD) patients, with greatest atrophy commonly found in posterior regions in the PCA group, whereas in the tAD group, atrophy is most prominent in medial temporal lobe regions. However, differential longitudinal atrophy patterns are not well understood. METHODS: This study assessed longitudinal changes in brain and gray matter volumes in 17 PCA patients, 16 tAD patients, and 18 healthy control subjects. Both patient groups had symptom durations of approximately 5 years. RESULTS: Progressive gray matter losses in both PCA and tAD patients were relatively widespread throughout the cortex, compared with control subjects, and were not confined to areas related to initial symptomatology. A multivariate classification analysis revealed a statistically significant group separation between PCA and tAD patients, with 72.7% accuracy (P < .01). CONCLUSION: Progression from an initially focal presentation to a more global pattern suggests that these different clinical presentations of AD might converge pathologically over time.

Visualizing the emergence of posterior cortical atrophy.

Posterior cortical atrophy (PCA) is a neurodegenerative condition characterized by a progressive loss of visual processing skills and other posterior functions. Diagnosis is often delayed in PCA as symptoms can be difficult for the patient to articulate and for the clinician to detect. Diagnosis is particularly challenging in the earliest stages of the disease since visual symptoms are often mistaken as being related to ocular rather than cortical dysfunction. This report describes a 61-year-old man who volunteered as a healthy control participant in a longitudinal research study and was followed up for 5 years. During that time he showed a gradual decline in posterior cortical functions including visuoperceptual, visuospatial, and literacy impairments in the context of intact verbal episodic memory. Structural image analysis revealed atrophy which was initially most marked in inferior temporal and posterior parietal cortices before spreading to occipital cortices and subsequently to more anterior regions. Based on the clinical, neuropsychological and neuroimaging features, a diagnosis of PCA was made. The present case represents a unique opportunity to study and visualize the evolution of PCA from the very earliest symptomatic stages.

Taxonomic and thematic organisation of proper name conceptual knowledge.

We report the investigation of the organisation of proper names in two aphasic patients (NBC and FBI). The performance of both patients on spoken word to written word matching tasks was inconsistent, affected by presentation rate and semantic relatedness of the competing responses, all hallmarks of a refractory semantic access dysphasia. In a series of experiments we explored the semantic relatedness effects within their proper name vocabulary, including brand names and person names. First we demonstrated the interaction between very fine grain organisation and personal experience, with one patient with a special interest in the cinema demonstrating higher error rates when identifying the names of actors working in a similar film genre (e.g., action movies: Arnold Schwarzenegger, Bruce Willis, Sylvester Stallone, Mel Gibson) than those working in different genres (e.g., Arnold Schwarzenegger, Gregory Peck, Robin Williams, Gene Kelly). Second we compared directly two potential principles of semantic organisation - taxonomic and thematic. Furthermore we considered these principles of organisation in the context of the individuals' personal knowledge base. We selected topics matching the interests and experience of each patient, namely cinema and literature (NBC) and naval history (FBI). The stimulus items were arranged in taxonomic arrays (e.g., Jane Austen, Emily Bronte, Agatha Christie), thematic arrays (e.g., Jane Austen, Pride and Prejudice, Mr Darcy), and unrelated arrays (e.g., Jane Austen, Wuthering Heights, Hercule Poirot). We documented that different patterns of taxonomic and thematic organisation were constrained by whether the individual has limited knowledge, moderate knowledge or detailed knowledge of a particular vocabulary. It is suggested that moderate proper name knowledge is primarily organised by taxonomy whereas extensive experience results in a more detailed knowledge base in which theme is a powerful organising principle.

Basic visual function and cortical thickness patterns in posterior cortical atrophy.

Posterior cortical atrophy (PCA) is characterized by a progressive decline in higher-visual object and space processing, but the extent to which these deficits are underpinned by basic visual impairments is unknown. This study aimed to assess basic and higher-order visual deficits in 21 PCA patients. Basic visual skills including form detection and discrimination, color discrimination, motion coherence, and point localization were measured, and associations and dissociations between specific basic visual functions and measures of higher-order object and space perception were identified. All participants showed impairment in at least one aspect of basic visual processing. However, a number of dissociations between basic visual skills indicated a heterogeneous pattern of visual impairment among the PCA patients. Furthermore, basic visual impairments were associated with particular higher-order object and space perception deficits, but not with nonvisual parietal tasks, suggesting the specific involvement of visual networks in PCA. Cortical thickness analysis revealed trends toward lower cortical thickness in occipitotemporal (ventral) and occipitoparietal (dorsal) regions in patients with visuoperceptual and visuospatial deficits, respectively. However, there was also a lot of overlap in their patterns of cortical thinning. These findings suggest that different presentations of PCA represent points in a continuum of phenotypical variation.

Cortical thickness and voxel-based morphometry in posterior cortical atrophy and typical Alzheimer's disease.

A significant minority of Alzheimer's disease patients present with posterior cortical atrophy (PCA). PCA is characterized by visuospatial and visuoperceptual deficits, and relatively preserved memory, whereas patients with typical Alzheimer's disease (tAD) mostly present with early episodic memory deficits. We used two unbiased image analysis techniques to assess atrophy patterns in 48 PCA, 30 tAD, and 50 healthy controls. FreeSurfer was used to measure cortical thickness, and volumetric grey matter differences were assessed using voxel-based morphometry (VBM). Both PCA and tAD showed widespread reductions compared with controls using both techniques. Direct comparison of PCA and tAD revealed thinner cortex predominantly in the right superior parietal lobe in the PCA group compared with tAD, whereas the tAD group showed thinning in the left entorhinal cortex compared with PCA. Similar results were obtained in the VBM analysis. These distinct patterns of atrophy may have diagnostic utility. In a clinical context, a relatively spared medial temporal lobe in the presence of posterior parietal atrophy may imply PCA, and should not discount AD.

Abnormal visual phenomena in posterior cortical atrophy.

Individuals with posterior cortical atrophy (PCA) report a host of unusual and poorly explained visual disturbances. This preliminary report describes a single patient (CRO), and documents and investigates abnormally prolonged colour afterimages (concurrent and prolonged perception of colours complimentary to the colour of an observed stimulus), perceived motion of static stimuli, and better reading of small than large letters. We also evaluate CRO's visual and vestibular functions in an effort to understand the origin of her experience of room tilt illusion, a disturbing phenomenon not previously observed in individuals with cortical degenerative disease. These visual symptoms are set in the context of a 4-year longitudinal neuropsychological and neuroimaging investigation of CRO's visual and other cognitive skills. We hypothesise that prolonged colour after-images are attributable to relative sparing of V1 inhibitory interneurons; perceived motion of static stimuli reflects weak magnocellular function; better reading of small than large letters indicates a reduced effective field of vision; and room tilt illusion effects are caused by disordered integration of visual and vestibular information. This study contributes to the growing characterisation of PCA whose atypical early visual symptoms are often heterogeneous and frequently under-recognised.

Different patterns of spoken and written word comprehension deficit in aphasic stroke patients.

This study presents neuropsychological evidence for differences in the semantic representations underpinning spoken and written word comprehension. Potential modality-based discrepancies in the semantic system were examined by testing whether spoken word (auditory-verbal input) and written word (visual-verbal input) comprehension exhibited the same effect profile on variables typically used to distinguish so-called access and storage disorders (e.g., response consistency, sensitivity to item frequency). The study was based on the premise that damage to a common set of semantic representations should have an equivalent impact upon comprehension performance irrespective of input modality, whereas damage to partially dissociable semantic representations may give rise to different qualities of deficit (access/storage) in the comprehension of stimuli presented in different input modalities (spoken/written). The study involved two patients with global aphasia following left middle cerebral artery stroke (F.B.I. and H.O.P.). The two patients showed matched performance on conventional tests of single word comprehension with clear evidence of semantic impairment for stimuli presented in both the spoken and written input modalities. However, in H.O.P., spoken and written word comprehension was affected in the same way by variations in stimulus category, frequency, and multiple stimulus presentations, whilst in F.B.I., there were clear differences between input modalities with all three variables. More specifically, F.B.I.'s written word comprehension was significantly affected by category (living > nonliving) and frequency (high > low) but not multiple presentations (single = multiple), more consistent with degradation of stored representations (storage deficit). By contrast, his spoken word comprehension was unaffected by category (living = nonliving) and frequency (high = low) but was affected by multiple presentations (single > multiple; serial position effects), more consistent with impaired access to stored representations (access deficit). These spoken/written input modality differences were observed on tasks matched closely for output modality, stimulus identity, and executive control requirements. It is argued that subtle differences in comprehension performance for stimuli presented in different input modalities may reflect damage to multimodal representations, which are intermediate between unimodal and amodal representations on a continuum of convergence within the semantic system. These ideas are discussed in the context of existing "distributed-only", "distributed-plus-convergence", or "distributed-plus-hub" models of conceptual knowledge.

The differential dependence of abstract and concrete words upon associative and similarity-based information: Complementary semantic interference and facilitation effects.

We report mirror-image effects of interference and facilitation in the semantic processing of identical sets of abstract and concrete words in a patient F.B.I. with global aphasia following a large left middle cerebral artery stroke. Interference was elicited when the tasks involved comprehending the spoken form of each word, but facilitation was found when the patient read aloud the written forms of the same words. More importantly, irrespective of whether the dynamic effect was one of facilitation or interference, effects of semantic association were observed for abstract words, whilst effects primarily of semantic similarity were observed for concrete words. These results offer further neuropsychological evidence that the more abstract a word, the greater its dependence upon associative information and the smaller its dependence upon similarity-based information. The investigations also contribute to a converging body of evidence that suggests that this theory generalizes across different experimental paradigms, stimuli, and participants and also across different cognitive processes within individual patients. The data support a graded rather than binary or ungraded model of the relationships between concreteness, association, and similarity, and the basis for concrete words' greater dependence upon similarity-based information is discussed in terms of the development of taxonomic structures and categorical thought in young children.