Cognitive and social cognitive functioning in spinocerebellar ataxia : a preliminary characterization.

INTRODUCTION: The spinocerebellar ataxias (SCAs), are rare neurodegenerative disorders caused by distinct genetic mutations. Clinically, the SCAs are characterised by progressive ataxia and a variety of other features, including cognitive dysfunction. The latter is consistent with a growing body of evidence supporting a cognitive as well as motor role for the cerebellum. Recent suggestions of cerebellar involvement in social cognition have not been extensively explored in these conditions. The availability of definitive molecular diagnosis allows genetically defined subgroups of SCA patients, with distinct patterns of cerebellar and extracerebellar involvement, to be tested comparatively using a common battery of tests of general, social and emotional cognition. METHODS: : Nine patients with SCA6, and 6 with SCA3 were assessed using a comprehensive battery of neuropsychological instruments, encompassing domains of memory, language, visuo-spatial skills, calculation, attention and executive function, emotional processing and theory of mind (ToM). RESULTS: There were no deficits in visuo-spatial processing or calculation in either group, while individuals with naming and attentional difficulties were seen in both. Deficits in memory and executive function were present in both conditions, albeit more pronounced in SCA3. By contrast, both groups demonstrated consistently poor performance on ToM tests, and normal attribution of social and emotional responses. CONCLUSION: The data support the hypothesis that the cerebellum is important for cognitive as well as motor activity. The pattern of overlap of domain impairments provides tentative preliminary evidence that there is a cerebellar contribution to aspects of memory and executive function and ToM, and that other domains depend more on neural system outside the cerebellum. The findings relating to ToM are relevant to the possibility of cerebellar involvement in autism.

A presenilin 1 R278I mutation presenting with language impairment.

Presenilin (PSEN)1 mutations are responsible for many cases of autosomal dominant Alzheimer disease (AD), although the clinical spectrum has not been fully defined. The authors describe two members of a kindred with a novel PSEN1 mutation (R278I) presenting with language impairment and relative preservation of memory. Screening for PSEN1 mutations may be appropriate in cases of familial dementia even where the clinical phenotype is not typical of AD.

Dissociation of lexical syntax and semantics: evidence from focal cortical degeneration.

The question of whether information relevant to meaning (semantics) and structure (syntax) relies on a common language processor or on separate subsystems has proved difficult to address definitively because of the confounds involved in comparing the two types of information. At the sentence level syntactic and semantic judgments make different cognitive demands, while at the single word level, the most commonly used syntactic distinction (between nouns and verbs) is confounded with a fundamental semantic difference (between objects and actions). The present study employs a different syntactic contrast (between count nouns and mass nouns), which is crossed with a semantic difference (between naturally occurring and man-made substances) applying to words within a circumscribed semantic field (foodstuffs). We show, first, that grammaticality judgments of a patient with semantic dementia are indistinguishable from those of a group of age-matched controls, and are similar regardless of the status of his semantic knowledge about the item. In a second experiment we use the triadic task in a group of age-matched controls to show that similarity judgments are influenced not only by meaning (natural vs. manmade), but also implicitly by syntactic information (count vs. mass). Using the same task in a patient with semantic dementia we show that the semantic influences on the syntactic dimension are unlikely to account for this pattern in normals. These data are discussed in relation to modular vs. nonmodular models of language processing, and in particular to the semantic-syntactic distinction.

Cognitive dysfunction after isolated brain stem insult. An underdiagnosed cause of long term morbidity.

Cognitive dysfunction adversely influences long term outcome after cerebral insult, but the potential for brain stem lesions to produce cognitive as well as physical impairments is not widely recognised. This report describes a series of seven consecutive patients referred to a neurological rehabilitation unit with lesions limited to brain stem structures, all of whom were shown to exhibit deficits in at least one domain of cognition. The practical importance of recognising cognitive dysfunction in this group of patients, and the theoretical significance of the disruption of specific cognitive domains by lesions to distributed neural circuits, are discussed.

Longitudinal profiles of semantic impairment for living and nonliving concepts in dementia of Alzheimer's type.

Two types of theoretical account have been proposed to explain the phenomenon of category-specific impairment in tests of semantic memory: One stresses the importance of different cortical regions to the representation of living and nonliving categories, while the other emphasize the importance of statistical relationships among features of concepts belonging to these two broad semantic domains. Theories of the latter kind predict that the direction of a domain advantage will be determined in large part by the overall damage to the semantic system, and that the profiles of patients with progressive impairments of semantic memory are likely to include a point at which an advantage for one domain changes to an advantage for the other. The present series of three studies employed semantic test data from two separate cohorts of patients with probable dementia of Alzheimer's type (DAT) to look for evidence of such a crossover. In the first study, longitudinal test scores from a cohort of 58 patients were examined to confirm the presence of progressive semantic deterioration in this group. In the second study, Kaplan-Meier survival curves based on serial naming responses and plotted separately for items belonging to living and nonliving domains indicated that the representations of living concepts (as measured by naming) deteriorated at a consistently and significantly faster rate than those of nonliving concepts. A third study, carried out to look in detail at the performance of mildly affected patients, employed an additional cross-sectional cohort of 20 patients with mild DAT and utilized a graded naming assessment. This study also revealed no evidence for a crossover in the advantage of one domain over the other as a function of disease severity. Taken together with the model of anatomical progression in DAT based on the work of Braak and Braak (1991), these findings are interpreted as evidence for the importance of regional cerebral anatomy to the genesis of semantic domain effects in DAT.

Semantic memory is impaired in both dementia with Lewy bodies and dementia of Alzheimer's type: a comparative neuropsychological study and literature review.

OBJECTIVE: To test the hypothesis that semantic impairment is present in both patients with dementia with Lewy bodies (DLB) and those with dementia of Alzheimer's type (DAT). METHODS: A comprehensive battery of neuropsychological tasks designed to assess semantic memory, visuoperceptual function, verbal fluency, and recognition memory was given to groups of patients with DLB (n=10), DAT (n=10) matched pairwise for age and mini mental state examination (MMSE), and age matched normal controls (n=15). RESULTS: Both DLB and DAT groups exhibited impaired performance across the range of tasks designed to assess semantic memory. Whereas patients with DAT showed equivalent comprehension of written words and picture stimuli, patients with DLB demonstrated more severe semantic deficits for pictures than words. As in previous studies, patients with DLB but not those with DAT were found to have impaired visuoperceptual functioning. Letter and category fluency were equally reduced for the patients with DLB whereas performance on letter fluency was significantly better in the DAT group. Recognition memory for faces and words was impaired in both groups. CONCLUSIONS: Semantic impairment is not limited to patients with DAT. Patients with DLB exhibit particular problems when required to access meaning from pictures that is most likely to arise from a combination of semantic and visuoperceptual impairments.

Prototypicality, distinctiveness, and intercorrelation: Analyses of the semantic attributes of living and nonliving concepts.

Many cognitive psychological, computational, and neuropsychological approaches to the organisation of semantic memory have incorporated the idea that concepts are, at least partly, represented in terms of their fine-grained features. We asked 20 normal volunteers to provide properties of 64 concrete items, drawn from living and nonliving categories, by completing simple sentence stems (e.g., an owl is __, has __, can__). At a later date, the same participants rated the same concepts for prototypicality and familiarity. The features generated were classified as to type of knowledge (sensory, functional, or encyclopaedic), and also quantified with regard to both dominance (the number of participants specifying that property for that concept) and distinctiveness (the proportion of exemplars within a conceptual category of which that feature was considered characteristic). The results demonstrate that rated prototypicality is related to both the familiarity of the concept and its distance from the average of the exemplars within the same category (the category centroid). The feature database was also used to replicate, resolve, and extend a variety of previous observations on the structure of semantic representations. Specifically, the results of our analyses (1) resolve two conflicting claims regarding the relative ratio of sensory to other kinds of attributes in living vs. nonliving concepts; (2) offer new information regarding the types of features-across different domains-that distinguish concepts from their category coordinates; and (3) corroborate some previous claims of higher intercorrelations between features of living things than those of artefacts.

Semantic dementia: clinical, radiological and pathological perspectives.

Semantic dementia (SD) is a recently described clinical syndrome characterised by an acquired progressive inability to name or comprehend common concepts, with little or no distortion of the phonological and syntactic aspects of language, and relative sparing of other aspects of cognition, such as episodic memory, nonverbal problem-solving, and perceptual and visuo-spatial skills. The cognitive locus of this syndrome appears to lie in the permanent store of long-term memory representing general world knowledge-semantic memory. The anatomical distribution of atrophy is less well-defined, and the contribution of various imaging modalities is discussed in the context of a body of 45 published and unpublished cases. We conclude that involvement of the left infero-lateral temporal cortex is the critical area in the genesis of SD. SD probably always represents a non-Alzheimer neurodegenerative process; a variety of pathological lesions may be present, and possible causes, together with debates about their correct classification, are discussed.

Non-verbal semantic impairment in semantic dementia.

The clinical presentation of patients with semantic dementia is dominated by anomia and poor verbal comprehension. Although a number of researchers have argued that these patients have impaired comprehension of non-verbal as well as verbal stimuli, the evidence for semantic deterioration is mainly derived from tasks that include some form of verbal input or output. Few studies have investigated semantic impairment using entirely non-verbal assessments and the few exceptions have been based on results from single cases ([3]: Breedin SD, Saffran EM, Coslett HB. Reversal of the concreteness effect in a patient with semantic dementia. Cognitive Neuropsychology 1994;11:617-660, [12]: Graham KS, Becker JT, Patterson K, Hodges JR. Lost for words: a case of primary progressive aphasia? In: Parkin A, editor. Case studies in the neuropsychology of memory, East Sussex: Lawrence Erlbaum, 1997. pp. 83-110, [21]: Lambon Ralph MA, Howard D. Gogi aphasia or semantic dementia? Simulating and assessing poor verbal comprehension in a case of progressive fluent aphasia. Cognitive Neuropsychology, (in-press). This study employed sound recognition and semantic association tasks to investigate the nature of the verbal and non-verbal comprehension deficit in 10 patients with semantic dementia. The patients were impaired on both verbal and non-verbal conditions of the assessments, and their accuracy on these tasks was directly related to their scores on a range of other tests requiring access to semantic memory. Further analyses revealed that performance was graded by concept and sound familiarity and, in addition, identified significant item consistency across the different conditions of the tasks. These results support the notion that the patients' deficits across all modalities were due to degradation within a single, central network of conceptual knowledge. There were also reliable differences between conditions. The sound-picture matching task proved to be more sensitive to semantic impairment than the word-picture matching equivalent, and the patients performed significantly better on the picture than word version of a semantic association test. We propose that these differences arise directly from the nature of the mapping between input modality and semantic memory. Words and sounds have an arbitrary relationship with meaning while pictures benefit from a degree of systematicity with conceptual knowledge about the object.

The differentiation of semantic dementia and frontal lobe dementia (temporal and frontal variants of frontotemporal dementia) from early Alzheimer's disease: a comparative neuropsychological study.

The authors compared age-matched groups of patients with the frontal and temporal lobe variants of frontotemporal dementia (FTD; dementia of frontal type [DFT] and semantic dementia), early Alzheimer's disease (AD), and normal controls (n = 9 per group) on a comprehensive neuropsychological battery. A distinct profile emerged for each group: Those with AD showed a severe deficit in episodic memory with more subtle, but significant, impairments in semantic memory and visuospatial skills; patients with semantic dementia showed the previously documented picture of isolated, but profound, semantic memory breakdown with anomia and surface dyslexia but were indistinguishable from the AD group on a test of story recall; and the DFT group were the least impaired and showed mild deficits in episodic memory and verbal fluency but normal semantic memory. The frontal and temporal presentations of FTD are clearly separable from each other and from early AD.

Category specific semantic loss in dementia of Alzheimer's type. Functional-anatomical correlations from cross-sectional analyses.

In the context of focal brain injury, selective loss of semantic knowledge in the domain of either natural kinds or artefacts is usually considered to reflect the differential importance of temporal and frontoparietal regions to the representations of perceptual and functional attributes, respectively. It is harder to account far as a feature of a more diffuse process, and previous cross-sectional analyses of patients with dementia of Alzheimer's type (DAT) have differed over whether category effects occur. In our series of 58 patients with probable DAT, we demonstrated a significant group advantage for artefacts, and explored possible reasons for the inconsistency of this finding in other studies. A multiple single-case strategy revealed not only individuals with consistent advantages for artefacts but also individuals with consistent advantages for natural kinds. By ranking the individuals according to measures of naming performance and global intellectual ability, we showed that the strength of the group advantage for artefacts was dependent on the former but not the latter variable. The findings are discussed in the context of two competing theories of semantic breakdown in DAT. One differentiates between domains of knowledge in terms of the structure of semantic representations within a single distributed network; the other emphasizes the importance of different brain regions in the category distinction. We conclude that our findings are in keeping with the predictions of the latter hypothesis.

The unit structure of the locust compound eye.

1. The ommatidium or functional unit of the locust compound eye comprises a compound corneal lens, 4 cone cells, 2 primary pigment cells, 16 secondary pigment cells and 8 retinula cells. 2. All retinula cells run the entire length from the cone to the basal lamina, although two, called the proximal cells, only contribute to the lowest third of the rhabdom, and one of either cell 6 or cell 7 on our arbitrary numbering system forms its axon one third the way up the ommatidium. 3. 84% of the 417 ommatidia examined had five cone cell processes. The position of three cone cell processes (cone threads) is almost invariable with respect to numbered retinula cells but the remaining threads can take any of three intercellular locations. 4. The position of these threads correlates with the number of the cell distally displaced from the rhabdom. We suggest that cone thread position in the developing ommatidium determines some features of retinula cells and we propose a simple model to account for this.