Thesis Abstract Objectives: The aim of this thesis is to add to the knowledge base on semantic memory (SM) in temporal lobe epilepsy (TLE) following unilateral resection. Method: A systematically informed literature review was completed to identify existing literature. By reviewing the literature, a shortage of studies evaluating SM in this patient group was identified. It also highlighted disparity in objective measurement of SM. An under representation of subjective measurement via self-report was discovered, no apparent reason for this was identified. This literature review informed and provided the rationale behind a correlational study between objective and subjective assessment of SM. Using a case series methodology, SM was reviewed in a sample of 20 people with TLE who had undergone surgery. The aim was to compare self-reported SM difficulties with a standardised SM assessment. Self-report was also explored using content analysis to look at quality of life. Results: There was one significant finding with respect to self-report and neuropsychological tests, this was between self-reported problems with ‘understanding conversations’ and The 64-Naming Test, taken from the Cambridge Semantic Battery (Bozeat et al., 2000). Sensitive measures and sensitive questioning of SM were found to aid identification of changes in SM. In general, self-report ratings of memory were not significantly correlated with objective neuropsychological testing. Exploration of self-report data highlighted that an equal number of left (78%) and right TLE (73%) patients reported problems with SM. Five key themes were identified representing positive and negative factors post-surgery; emotional issues (65%) and adjustment issues (55%) predominated. Psychological issues seemed to reflect reports of depression more than anxiety. Discussion: Participants post-surgery were more sensitive to naming impairments than other forms of SM impairments. Self-report of naming impairments may indicate semantic processing difficulties, and therefore may be a valuable method to aid clinical assessment. Conclusions: Supplementing objective measurement with sensitive self-report assessment is useful in clinical practice.

Contemporary clinical and basic neuroscience studies have increasingly implicated the anterior temporal lobe regions, bilaterally, in the formation of coherent concepts. Mounting convergent evidence for the importance of the anterior temporal lobe in semantic memory is found in patients with bilateral anterior temporal lobe damage (e.g. semantic dementia), functional neuroimaging and repetitive transcranial magnetic stimulation studies. If this proposal is correct, then one might expect patients with anterior temporal lobe resection for long-standing temporal lobe epilepsy to be semantically impaired. Such patients, however, do not present clinically with striking comprehension deficits but with amnesia and variable anomia, leading some to conclude that semantic memory is intact in resection for temporal lobe epilepsy and thus casting doubt over the conclusions drawn from semantic dementia and linked basic neuroscience studies. Whilst there is a considerable neuropsychological literature on temporal lobe epilepsy, few studies have probed semantic memory directly, with mixed results, and none have undertaken the same type of systematic investigation of semantic processing that has been conducted with other patient groups. In this study, therefore, we investigated the semantic performance of 20 patients with resection for chronic temporal lobe epilepsy with a full battery of semantic assessments, including more sensitive measures of semantic processing. The results provide a bridge between the current clinical observations about resection for temporal lobe epilepsy and the expectations from semantic dementia and other neuroscience findings. Specifically, we found that on simple semantic tasks, the patients' accuracy fell in the normal range, with the exception that some patients with left resection for temporal lobe epilepsy had measurable anomia. Once the semantic assessments were made more challenging, by probing specific-level concepts, lower frequency/more abstract items or measuring reaction times on semantic tasks versus those on difficulty-matched non-semantic assessments, evidence of a semantic impairment was found in all individuals. We conclude by describing a unified, computationally inspired framework for capturing the variable degrees of semantic impairment found across different patient groups (semantic dementia, temporal lobe epilepsy, glioma and stroke) as well as semantic processing in neurologically intact participants.

Aphasic patients with multimodal semantic impairment following pFC or temporo-parietal (TP) cortex damage (semantic aphasia [SA]) have deficits characterized by poor control of semantic activation/retrieval, as opposed to loss of semantic knowledge per se. In line with this, SA patients show “refractory effects”; that is, declining accuracy in cyclical word–picture matching tasks when semantically related sets are presented rapidly and repeatedly. This is argued to follow a build-up of competition between targets and distractors. However, the link between poor semantic control and refractory effects is still controversial for two reasons. (1) Some theories propose that refractory effects are specific to verbal or auditory tasks, yet SA patients show poor control over semantic processing in both word and picture semantic tasks. (2) SA can result from lesions to either the left pFC or TP cortex, yet previous work suggests that refractory effects are specifically linked to the left inferior frontal cortex. For the first time, verbal, visual, and nonverbal auditory refractory effects were explored in nine SA patients who had pFC (pFC+) or TP cortex (TP-only) lesions. In all modalities, patient accuracy declined significantly over repetitions. This refractory effect at the group level was driven by pFC+ patients and was not shown by individuals with TP-only lesions. These findings support the theory that SA patients have reduced control over multimodal semantic retrieval and, additionally, suggest there may be functional specialization within the posterior versus pFC elements of the semantic control network.

Background: Linguistic knowledge makes an important contribution to verbal STM. Some theories, including Baddeley's original conception of the episodic buffer, hold that harnessing linguistic knowledge to support STM is executively demanding. However, some recent evidence suggests that the linguistic contribution does not depend on executive resources. Aims: In this study we tested the hypothesis that activation of language representations is automatic and that executive control is most important when the material to be remembered is incompatible with this automatic activation. Methods & Procedures: Word list recall was tested in three patients with transcortical sensory aphasia (TSA) following stroke. All had preserved word repetition and digit span but poor comprehension associated with impaired executive control. They were compared with two semantic dementia (SD) patients with degraded semantic representations but intact executive control. Patients repeated word lists that varied in their semantic and syntactic resemblance to meaningful sentences. Outcomes & Results: The executively impaired TSA patients showed large benefits of semantic and syntactic structure, indicating that their executive deficits did not interfere with the normal linguistic contribution to STM. Instead they showed severe deficits in repetition of scrambled word lists that did not follow usual syntactic rules. On these, the patients changed the word order to better fit their existing knowledge of syntactic structure. In contrast, the SD patients had no problems repeating words in unusual sequences but their semantic knowledge degradation led to frequent phonological errors due to a loss of “semantic binding”, the process by which semantic knowledge of words helps to constrain their phonological representation. Conclusions: These findings suggest that linguistic support for STM consists of (a) automatic activation of semantic and syntactic knowledge and (b) executive processes that inhibit this activation when it is incompatible with the material to be remembered.

When relearning words, patients with semantic dementia (SD) exhibit a characteristic rigidity, including a failure to generalise names to untrained exemplars of trained concepts. This has been attributed to an over-reliance on the medial temporal region which captures information in sparse, non-overlapping and therefore rigid representations. The current study extends previous investigations of SD relearning by re-examining the additional contribution made by the degraded cortical semantic system. The standard relearning protocol was modified by careful selection of foils to show that people with semantic dementia were sometimes able to extend their learning appropriately but that this correct generalisation was minimal (i.e. the patients under-generalised their learning). The revised assessment procedure highlighted the fact that, after relearning, the participants also incorrectly over-generalised the learned label to closely related concepts. It is unlikely that these behaviours would occur if the participants had only formed sparse hippocampal representations. These novel data build on the notion that people with semantic dementia engage both the degraded cortical semantic (neocortex) and the episodic (medial temporal) systems to learn. Because of neocortical damage to the anterior temporal lobes, relearning is disordered with a characteristic pattern of under- and over-generalisation.

Patients with semantic dementia (SD) have anterior temporal lobe (ATL) atrophy that gives rise to a highly selective deterioration of semantic knowledge. Despite pronounced anomia and poor comprehension of words and pictures, SD patients have well-formed, fluent speech and normal digit span. Given the intimate connection between phonological STM and word learning revealed by both neuropsychological and developmental studies, SD patients might be expected to show good acquisition of new phonological forms, even though their ability to map these onto meanings is impaired. In contradiction of these predictions, a limited amount of previous research has found poor learning of new phonological forms in SD. In a series of experiments, we examined whether SD patient, GE, could learn novel phonological sequences and, if so, under which circumstances. GE showed normal benefits of phonological knowledge in STM (i.e., normal phonotactic frequency and phonological similarity effects) but reduced support from semantic memory (i.e., poor immediate serial recall for semantically degraded words, characterised by frequent item errors). Next, we demonstrated normal learning of serial order information for repeated lists of single-digit number words using the Hebb paradigm: these items were well-understood allowing them to be repeated without frequent item errors. In contrast, patient GE showed little learning of nonsense syllable sequences using the same Hebb paradigm. Detailed analysis revealed that both GE and the controls showed a tendency to learn their own errors as opposed to the target items. Finally, we showed normal learning of phonological sequences for GE when he was prevented from repeating his errors. These findings confirm that the ATL atrophy in SD disrupts phonological processing for semantically degraded words but leaves the phonological architecture intact. Consequently, when item errors are minimised, phonological STM can support the acquisition of new phoneme sequences in patients with SD.

Background: Semantic dementia (SD) is a disorder that leads to a gradual but profound breakdown of conceptual knowledge and, as a result, severe anomia that is not alleviated by phonemic cueing. Several studies have shown that practising to name a set of objects can help people with SD to relearn the names of those objects. However, it is not clear whether the factors that impact on spontaneous naming in SD would remain the same or whether they would change as a result of relearning. Aims: The current relearning study examined phonemic cueing before and after relearning, to determine whether this factor's impact on naming changed during the course of the relearning. Methods & Procedures: Two people with SD participated in the study. A baseline naming test was performed prior to the start of the relearning. The relearning took place over 3 weeks (15 sessions), followed immediately by a retest the following day. Relearning and the influence of phonemic cueing were measured at baseline and retest. Outcomes & Results: The impact of phonemic cueing was greater at retest than at baseline. Conclusions: Although phonemic cueing did not impact on spontaneous naming in SD, it did have a facilitative effect after relearning. This change may signal a shift in the relative contributions of the underlying learning systems.

Disorders of semantic cognition in different neuropsychological conditions result from diverse areas of brain damage and may have different underlying causes. This study used a comparative case-series design to examine the hypothesis that relatively circumscribed bilateral atrophy of the anterior temporal lobe in semantic dementia (SD) produces a gradual degradation of core semantic representations, whilst a deficit of cognitive control produces multi-modal semantic impairment in a subset of patients with stroke aphasia following damage involving the left prefrontal cortex or regions in and around the temporoparietal area; this condition, which transcends traditional aphasia classifications, is referred to as 'semantic aphasia' (SA). There have been very few direct comparisons of these patient groups to date and these previous studies have focussed on verbal comprehension. This study used a battery of object-use tasks to extend this line of enquiry into the non-verbal domain for the first time. A group of seven SA patients were identified who failed both word and picture versions of a semantic association task. These patients were compared with eight SD cases. Both groups showed significant deficits in object use but these impairments were qualitatively different. Item familiarity correlated with performance on object-use tasks for the SD group, consistent with the view that core semantic representations are degrading in this condition. In contrast, the SA participants were insensitive to the familiarity of the objects. Further, while the SD patients performed consistently across tasks that tapped different aspects of knowledge and object use for the same items, the performance of the SA participants reflected the control requirements of the tasks. Single object use was relatively preserved in SA but performance on complex mechanical puzzles was substantially impaired. Similarly, the SA patients were able to complete straightforward item matching tasks, such as word-picture matching, but performed more poorly on associative picture-matching tasks, even when the tests involved the same items. The two groups of patients also showed a different pattern of errors in object use. SA patients made substantial numbers of erroneous intrusions in their demonstrations, such as inappropriate object movements. In contrast, response omissions were more common in SD. This study provides converging evidence for qualitatively different impairments of semantic cognition in SD and SA, and uniquely demonstrates this pattern in a non-verbal expressive domain-object use.

Semantic aphasia (SA) refers to a subset of aphasic patients who exhibit multimodal semantic deficits (Jefferies, E., & Lambon Ralph, M. (2006). Semantic impairment in stroke aphasia vs semantic dementia: a case-series comparison. Brain, 129(8), 2132–2147). Consistent with their underlying semantic control deficit, SA picture naming accuracy can be improved considerably with a correct phonological cue. The performance of normal individuals in the tempo picture naming paradigm reveals an increased impact of both correct and incorrect phonological cueing, and it has been suggested that this technique reduces resources available for semantic control in neurologically-intact participants (Hodgson, C., & Lambon Ralph, M. (2008). Mimicking aphasic semantic naming errors in normal speech production: Evidence from a novel experimental paradigm. Brain and Language, 104(1), 89–101.). We tested this hypothesis by considering the impact of both correct and incorrect phonological cues on picture naming in a case series of SA patients, using exactly the same items as those presented to normal participants for tempo naming. The results confirmed the positive effect of correct cues and revealed for the first time the negative effects of category co-ordinate miscues amongst these patients in both overall accuracy and semantic error rates. The implications of our results for current speech production models are considered.

Semantic short-term memory (STM) patients have a reduced ability to retain semantic information over brief delays but perform well on other semantic tasks; this pattern suggests damage to a dedicated buffer for semantic information. Alternatively, these difficulties may arise from mild disruption to domain-general semantic processes that have their greatest impact on demanding STM tasks. In this study, mild semantic processing impairments were demonstrated in 2 semantic STM patients. They performed well on untimed semantic tasks but were deficient in accuracy and reaction times on speeded tasks. Demanding semantic production tasks were also affected. These patients were compared with a case series of individuals with semantic aphasia whose multimodal semantic difficulties stemmed from poor cognitive control. STM and semantic performance were more impaired in this group, but there were qualitative similarities to the semantic STM patients. The difference between the 2 patient types may be a matter of degree. In semantic aphasia, severe disruption to semantic control leads to global semantic impairments, whereas in semantic STM milder disruption might impact mainly on STM tests because of the high control demands of these tasks.

Patients with semantic dementia (SD) make numerous phoneme migration errors when recalling lists of words they no longer fully understand, suggesting that word meaning makes a critical contribution to phoneme binding in verbal short-term memory. Healthy individuals make errors that appear similar when recalling lists of nonwords, which also lack semantic support. Although previous studies have assumed that the errors in these two groups stem from the same underlying cause, they have never been directly compared. We tackled this issue by examining immediate serial recall for SD patients and controls on "pure" word lists and "mixed" lists that contained a mixture of words and nonwords. SD patients were equally poor at pure and mixed lists and made numerous phoneme migration errors in both conditions. In contrast, controls recalled pure lists better than mixed lists and only produced phoneme migrations for mixed lists. We also examined the claim that semantic activation is critical for words in the primacy portion of the list. In fact, the effect of mixed lists was greatest for later serial positions in the control group and in the SD group recall was poorest towards the ends of lists. These results suggest that mixing nonwords with words in healthy participants closely mimics the impact of semantic degradation in SD on word list recall. The study provides converging evidence for the idea that lexical/semantic knowledge is an important source of constraint on phonological coherence, ensuring that phonemes in familiar words are bound to each other and emerge together in recall.

In the last few years, a number of connectionist models have been described that provide an explanation for age-of-acquisition (AoA) effects in verbal and nonverbal tasks. Further simulations and an empirical study were conducted to test two predictions that arise from these models. The first prediction is that AoA effects will be modulated by the nature of the mapping between representations; effects should be largest for arbitrary mappings (i.e., where there is no relationship between input and output representations such as that found in mapping semantics to phonology, e. g., picture naming), smaller for systematic mappings and minimal for componential representations (such as those found in mapping orthography to phonology for languages with relatively transparent orthographies). The second prediction from the models is that not only AoA but also frequency should influence performance and that these two variables might interact. These two predictions were tested in an empirical study. Performance on a set of 80 picturable nouns that orthogonally varied AoA and word frequency was directly compared in picture and word naming experiments. As predicted, there was a dramatic interaction between AoA and task, with substantial AoA effects in picture naming but not word naming. In addition, there was evidence for an interaction between AoA and frequency in both tasks. These results highlight the importance of the computational mapping between representations when considering both the likely performance in any task and the influence of any underlying factors.