Evidence for degraded low frequency verbal concepts in left resected temporal lobe epilepsy patients.

According to a large neuropsychological and neuroimaging literature, the bilateral anterior temporal lobe (ATL) is a core region for semantic processing. It seems therefore surprising that semantic memory appears to be preserved in temporal lobe epilepsy (TLE) patients with unilateral ATL resection. However, recent work suggests that the bilateral semantic system is relatively robust against unilateral damage and semantic impairments under these circumstances only become apparent with low frequency specific concepts. In addition, neuroimaging studies have shown that the function of the left and right ATLs differ and therefore left or right ATL resection should lead to a different pattern of impairment. The current study investigated hemispheric differences in the bilateral semantic system by comparing left and right resected TLE patients during verbal semantic processing of low frequency concepts. Picture naming and semantic comprehension tasks with varying word frequencies were included to investigate the pattern of impairment. Left but not right TLE patients showed impaired semantic processing, which was particularly apparent on low frequency items. This indicates that, for verbal information, the bilateral semantic system is more sensitive to damage in the left compared to the right ATL, which is in line with theories that attribute a more prominent role to the left ATL due to connections with pre-semantic verbal regions.

The 'when' and 'where' of semantic coding in the anterior temporal lobe: Temporal representational similarity analysis of electrocorticogram data.

Electrocorticograms (ECoG) provide a unique opportunity to monitor neural activity directly at the cortical surface. Ten patients with subdural electrodes covering ventral and lateral anterior temporal regions (ATL) performed a picture naming task. Temporal representational similarity analysis (RSA) was used, for the first time, to compare spatio-temporal neural patterns from the ATL surface with pre-defined theoretical models. The results indicate that the neural activity in the ventral subregion of the ATL codes semantic representations from 250 msec after picture onset. The observed activation similarity was not related to the visual similarity of the pictures or the phonological similarity of their names. In keeping with convergent evidence for the importance of the ATL in semantic processing, these results provide the first direct evidence of semantic coding from the surface of the ventral ATL and its time-course.

Differential contributions of bilateral ventral anterior temporal lobe and left anterior superior temporal gyrus to semantic processes.

Studies of semantic dementia and repetitive TMS have suggested that the bilateral anterior temporal lobes (ATLs) underpin a modality-invariant representational hub within the semantic system. However, it is not clear whether all ATL subregions contribute in the same way. We utilized distortion-corrected fMRI to investigate the pattern of activation in the left and right ATL when participants performed a semantic decision task on auditory words, environmental sounds, or pictures. This showed that the ATL is not functionally homogeneous but is more graded. Both left and right ventral ATL (vATL) responded to all modalities in keeping with the notion that this region underpins multimodality semantic processing. In addition, there were graded differences across the hemispheres. Semantic processing of both picture and environmental sound stimuli was associated with equivalent bilateral vATL activation, whereas auditory words generated greater activation in left than right vATL. This graded specialization for auditory stimuli would appear to reflect the input from the left superior ATL, which responded solely to semantic decisions on the basis of spoken words and environmental sounds, suggesting that this region is specialized to auditory stimuli. A final noteworthy result was that these regions were activated for domain level decisions to singly presented stimuli, which appears to be incompatible with the hypotheses that the ATL is dedicated (a) to the representation of specific entities or (b) for combinatorial semantic processes.

Semantic processing in the anterior temporal lobes: a meta-analysis of the functional neuroimaging literature.

The role of the anterior temporal lobes (ATLs) in semantic cognition is not clear from the current literature. Semantic dementia patients show a progressive and a specific semantic impairment, following bilateral atrophy of the ATLs. Neuroimaging studies of healthy participants, however, do not consistently show ATL activation during semantic tasks. Consequently, several influential theories of semantic memory do not ascribe a central role to the ATLs. We conducted a meta-analysis of 164 functional neuroimaging studies of semantic processing to investigate factors that might contribute to the inconsistency in previous results. Four factors influenced the likelihood of finding ATL activation: (1) the use of PET versus fMRI, reflecting the fact that fMRI but not PET is sensitive to distortion artifacts caused by large variations in magnetic susceptibility in the area of the ATL; (2) a field of view (FOV) of more than 15 cm, thereby ensuring whole-brain coverage; (3) the use of a high baseline task to prevent subtraction of otherwise uncontrolled semantic activation; (4) the inclusion of the ATL as an ROI. The type of stimuli or task did not influence the likelihood of ATL activation, consistent with the view that this region underpins an amodal semantic system. Spoken words, written words, and picture stimuli produced overlapping ATL peaks. On average, these were more inferior for picture-based tasks. We suggest that the specific pattern of ATL activation may be influenced by stimulus type due to variations across this region in the degree of connectivity with modality-specific areas in posterior temporal cortex.

Relative preservation of 'animate' knowledge in an atypical presentation of herpes simplex virus encephalitis.

A comprehensive battery of neuropsychological tests designed to assess primary cognitive functions, including language and semantic memory, was given to MG, a patient with confirmed herpes simplex virus encephalitis. MG's initial jargon aphasia resolved over time to leave her with a mild phonological impairment. She had a very mild amnesia that was worse for verbal material and a category-specific impairment of semantic memory. This latter impairment resulted in a significant anomia that was worse for manmade/artefact items than for animate kinds. Her naming difficulties were associated with a mild impairment in comprehension that was not specific to category or feature type. MRI revealed a strongly asymmetric and atypical distribution of pathology in MG with the disease affecting the left medial temporal lobe, temporal pole, left frontotemporal and temporoparietal regions.

Implicit word cues facilitate impaired naming performance: evidence from a case of anomia.

Word-finding difficulties observed in some patients with anomia have been attributed to an insufficient activation of phonology by semantics. There are, however, few direct tests of this hypothesis. This paper reports the case of FR, who presented with anomic aphasia following temporal lobe epilepsy and a cavernoma in the left superior temporal lobe. His anomic deficit was characterized by: (1) no apparent associated semantic impairment; (2) item consistency for accuracy and errors across different administrations; (3) accuracy strongly correlated with word frequency; and (4) a partial, albeit weak, knowledge of the gender of unnamed items. We conducted a naming experiment in which target pictures were implicitly primed by briefly presented masked words. Results showed that the prior presentation of the written target name improved accuracy. When compared with unprimed trials, the presence of the primes also increased phonological errors and decreased semantic errors. We argue that automatic phonological activation derived directly from the implicit written primes interacted with the remaining phonological input from the picture's semantic representation leading to increased accuracy and a change in the balance of error types.

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.

Differing patterns of temporal atrophy in Alzheimer's disease and semantic dementia.

OBJECTIVE: To characterize and quantify the patterns of temporal lobe atrophy in AD vs semantic dementia and to relate the findings to the cognitive profiles. Medial temporal lobe atrophy is well described in AD. In temporal variant frontotemporal dementia (semantic dementia), clinical studies suggest polar and inferolateral temporal atrophy with hippocampal sparing, but quantification is largely lacking. METHODS: A volumetric method for quantifying multiple temporal structures was applied to 26 patients with probable AD, 18 patients with semantic dementia, and 21 matched control subjects. RESULTS: The authors confirmed the expected bilateral hippocampal atrophy in AD relative to controls, with involvement of the amygdala bilaterally and the right parahippocampal gyrus. Contrary to expectations, patients with semantic dementia had asymmetric hippocampal atrophy, more extensive than AD on the left. As predicted, the semantic dementia group showed more severe involvement of the temporal pole bilaterally and the left amygdala, parahippocampal gyrus (including the entorhinal cortex), fusiform gyrus, and the inferior and middle temporal gyri. Performance on semantic association tasks correlated with the size of the left fusiform gyrus, whereas naming appeared to depend upon a wider left temporal network. Episodic memory measures, with the exception of recognition memory for faces, did not correlate with temporal measures. CONCLUSIONS: Hippocampal atrophy is not specific for AD but is also seen in semantic dementia. Distinguishing the patients with semantic dementia was the severe global but asymmetric (left > right) atrophy of the amygdala, temporal pole, and fusiform and inferolateral temporal gyri. These findings have implications for diagnosis and understanding of the cognitive deficits in AD and semantic dementia.

No right to speak? The relationship between object naming and semantic impairment: neuropsychological evidence and a computational model.

The processes required for object naming were addressed in a study of patients with semantic dementia (a selective decline of semantic memory resulting from progressive temporal lobe atrophy) and in a computational model of single-word production. Although all patients with semantic dementia are impaired in both single-word production and comprehension, previous reports had indicated two different patterns: (a) a parallel decline in accuracy of naming and comprehension, with frequent semantic naming errors, suggesting a purely semantic basis for the anomia and (b) a dramatic progressive anomia without commensurate decline in comprehension, which might suggest a mainly postsemantic source of the anomia. Longitudinal data for 16 patients with semantic dementia reflected these two profiles, but with the following additional important specifications: (1) despite a few relatively extreme versions of one or other profile, the full set of cases formed a continuum in the extent of anomia for a given degree of degraded comprehension; (2) the degree of disparity between these two abilities was associated with relative asymmetry in laterality of atrophy: a parallel decline in the two measures characterized patients with greater right- than left-temporal atrophy, while disproportionate anomia occurred with a predominance of atrophy in the left-temporal lobe. In an implemented computational model of naming, semantic representations were distributed across simulated left- and right-temporal regions, but the semantic units on the left were more strongly connected to left-lateralized phonological representations. Asymmetric damage to semantic units reproduced the longitudinal patient profiles of naming relative to comprehension, plus additional characteristics of the patients' naming performance. On the basis of both the neuropsychological and computational evidence, we propose that semantic impairment alone can account for the full range of word production deficits described here.

Deficits in irregular past-tense verb morphology associated with degraded semantic knowledge.

Two distinct mechanisms are often considered necessary to account for generation of the past-tense of English verbs: a lexical associative process for irregular forms like speak-->spoke, and a rule-governed process ("add -ed") for regular and novel forms like talk-->talked and wug-->wugged. An alternative account based on a parallel-distributed processing approach proposes that one complex procedure processes all past-tense types. In this alternative view, neuropsychological dissociations are explained by reduced input from word meaning that plays a greater role in successful generation of the past-tense for lower frequency irregular verbs, and by phonological deficits that disproportionately affect regular and novel forms. Only limited evidence has been available concerning the relationship between knowledge of word meaning and verb-tense processing. The study reported here evaluated the past-tense verb abilities of 11 patients with semantic dementia, a neurodegenerative condition characterised by degraded semantic knowledge. We predicted and confirmed that the patients would have essentially normal ability to generate and recognise regular (and novel) past-tense forms, but a marked and frequency-modulated deficit on irregular verbs. Across the set of 11 patients, the degree of impairment for the irregular past-tense was significantly correlated with the degree of comprehension impairment as measured by verb synonym judgements. These results, plus other features of the data such as the nature of the errors to irregular verbs, are discussed in relation to currently developing theories of the language system.

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.

Age of acquisition effects in adult lexical processing reflect loss of plasticity in maturing systems: insights from connectionist networks.

Early learned words are recognized and produced faster than later learned words. The authors showed that such age of acquisition effects are a natural property of connectionist models trained by back-propagation when patterns are introduced at different points into training and learning of early and late patterns is cumulative and interleaved. Analysis of hidden unit activations indicated that the age of acquisition effect reflects a gradual reduction in network plasticity and a consequent failure to differentiate late items as effectively as early ones. Further simulations examined the effects of vocabulary size, learning rate, sparseness of coding, use of a modified learning algorithm, loss of early items, acquisition of very late items, and lesioning the network. The relationship between age of acquisition and word frequency was explored, including analyses of how the relative influence of these factors is modulated by introducing weight decay.

The role of conceptual knowledge in object use evidence from semantic dementia.

It has been reported that patients with semantic dementia function well in everyday life and sometimes show striking preservation of the ability to use objects, even those specific objects for which the patient has degraded conceptual information. To explore this phenomenon in nine cases of semantic dementia, we designed a set of semantic tests regarding 20 everyday objects and compared performance on these with the patients' ability to demonstrate the correct use of the same items. We also administered a test of mechanical problem solving utilizing novel tools, on which the patients had completely normal ability. All but the mildest affected patient showed significant deficits of naming and on the visually based semantic matching tasks. Object use was markedly impaired and, most importantly, correlated strongly with naming and semantic knowledge. In a small number of instances, there was appropriate use of an object for which the patient's knowledge on the semantic matching tasks was no better than chance; but this typically applied to objects with a rather obvious relationship between appearance and use, or was achieved by trial and error. The results suggest that object use is heavily dependent upon object-specific conceptual knowledge, supplemented to some degree by a combination of visual affordances and mechanical problem solving.

The rise and fall of frequency and imageability: noun and verb production in semantic dementia.

This study examines the impact of progressive degeneration of conceptual knowledge on the content words used in connected speech elicited using the Cookie Theft picture description (Goodglass & Kaplan. 1983). We began with an analysis of control subjects' descriptions with regard to word types and their frequency and imageability. Because the impairment of conceptual knowledge in semantic dementia is graded by concept familiarity, we created a model of a standardized normal Cookie Theft description that was then progressively degraded by the systematic removal of lower bands of word frequency. We drew two main predictions from this model: reduced availability of the lower bands of word frequency should result in (a) an apparent deficit for noun retrieval in relation to verb retrieval and (b) an apparent reverse imageability effect. Results from a longitudinal study. in which three patients with semantic dementia each described the Cookie Theft picture on three occasions during the progression of their disease, confirmed these predictions. An additional cross-sectional analysis, adding narratives from a larger number of cases, demonstrated that the decline in ability to produce suitable words for the picture description is closely related to the extent of semantic impairment as measured in tests of word comprehension and production. Both verbs and nouns are affected by the degradation of semantic memory; the fact that the impairment to noun production is manifested earlier and more catastrophically may be attributed to the relatively lower frequency of these terms.

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.

Classical anomia: a neuropsychological perspective on speech production.

We present data collected from two anomic aphasics. Thorough assessment of comprehension, oral reading and repetition revealed no underlying impairments suggesting that both patients were examples of classical anomia--word-finding difficulties without impaired semantics or phonology. We describe a series of experiments in which the degree of anomia was both increased and decreased, by cueing or priming with either a semantically related word or the target item. One of the patients also presented with an 'acquired' tip-of-the-tongue phenomenon. He was able to indicate with a high-degree of accuracy the syllable length of the target, and whether or not it was a compound word. Neither patient could provide the first sound/letter. The data are discussed in terms of discrete two-stage models of speech production, an interactive-activation theory and a distributed model in which the positive and negative computational consequences of the arbitrary relationship between sound and meaning are emphasised.

Is a picture worth a thousand words? Evidence from concept definitions by patients with semantic dementia.

Nine patients with semantic dementia (the temporal lobe variant of frontotemporal dementia) were asked to define concrete concepts either from presentation of a picture of the object or from its spoken name. As expected, the patients with the most severe semantic impairment produced the least detailed definitions, and the quality of the definitions overall was significantly related to concept familiarity. Further analyses of the definitions were designed to assess two key theoretical aspects of semantic organization. (i) Do objects and their corresponding names activate conceptual information in two neuroanatomically separable (modality-specific) semantic systems? If so, then-apart from any expected commonality in performance attributable to factors such as concept familiarity-one would not predict striking item-specific similarities in a patient's picture- and word-elicited definitions. (ii) Do sensory/perceptual features and more associative/functional attributes of conceptual knowledge form two neuroanatomically separable subsystems? If so, then one would predict significant dissociations in the prominence of these two types of information in the patients' definitions. The results lead us to favor a model of the semantic system that is divided by attribute type but not by modality.

Naming in semantic dementia--what matters?

One of the major symptoms of semantic dementia (or progressive fluent aphasia) is profound word-finding difficulties. We present here a cross-sectional study of the factors affecting picture naming in semantic dementia based on data obtained from eight patients, together with a longitudinal analysis of naming in another patient. Various properties and attributes of the objects were entered into a series of regression analyses in order to predict which items the patients could or could not name. The analyses showed that object familiarity, word frequency and age-of-acquisition predicted naming success for the group and, in most cases, for each individual patient, irrespective of lesion site or overall naming success. We propose that the pattern of naming in semantic dementia is best described in terms of reduced semantic activation within a cascading/interactive speech production system. We suggest that object familiarity, and possibly word frequency, reflect the inherent robustness of individual semantic representations to the decay process in terms of both quantity and quality of experience. Age-of-acquisition and word frequency (at a phonological-lexical level) predicts naming success, because frequent, early-acquired words are relatively easy to activate even with reduced semantic "input".

The relationship between naming and semantic knowledge for different categories in dementia of Alzheimer's type.

We studied the relationship between naming and semantic memory in a group of 10 patients with dementia of Alzheimer's type. In an extension to a previous cross-sectional study (Hodges, J. R. et al., Brain and Language, 1996, 54, 302-325), this relationship was investigated at two longitudinal points within each patient's cognitive decline. Two types of naming performance were compared: items that each patient named correctly at the first stage but failed to name at the second stage, as contrasted with items named correctly at both stages (thereby providing a control for cognitive decline in general). Semantic knowledge of the concepts represented by the pictures in the naming test was investigated at each stage using definitions to the spoken object name, scored particularly for the number of sensory and associative/functional features provided by the patient. At stage 2, an analysis of the definitions for named-->unnamed items as contrasted with named-->named objects revealed a significant loss of both sensory and associative information. A comparison between natural kinds (animals and birds) and artefacts (household objects, vehicles, etc.), however, demonstrated a striking interaction between category and type of information contained in the definitions. Specifically, stage 2 definitions of artefacts in the named-->unnamed set showed a disproportionate loss of associative/functional information, while definitions of animal names that patients failed to produce in response to the pictures were notably lacking in sensory features. This pattern supports the notion that successful naming relies on a subset of critical semantic features which vary somewhat across different categories of semantic knowledge. We suggest that these findings are best encompassed by a conception of semantic organization, Weighted Overlappingly Organized Features (WOOF), in which (i) knowledge about all objects is represented by a central, distributed network of features activated by both words and pictures, but (ii) natural kinds and artefacts are differentially weighted in favour of those features that are involved in learning about and experiencing different kinds of objects.