Mapping eloquent cortex: A voxel-based lesion-symptom mapping study of core speech production capacities in brain tumour patients.

This study used voxel-based lesion-symptom mapping to examine the cortical and white matter regions associated with language production impairments in a sample of 63 preoperative tumour patients. We identified four cognitive functions considered crucial for spoken language production: semantic-to-lexical mapping (selecting the appropriate lexical label for the intended concept); phonological encoding (retrieving the word's phonological form); articulatory-motor planning (programming the articulatory motor movements); and goal-driven language selection (exerting top-down control over the words selected for production). Each participant received a score estimating their competence on each function. We then mapped the region(s) where pathology was significantly associated with low scores. For semantic-to-lexical mapping, the critical map encompassed portions of the left posterior middle and inferior temporal gyri, extending into posterior fusiform gyrus, overlapping substantially with the territory of the inferior longitudinal fasciculus. For phonological encoding, the map encompassed the left inferior parietal lobe and posterior middle temporal gyrus, overlapping with the territory of the inferior longitudinal and posterior arcuate fasciculi. For articulatory-motor planning, the map encompassed parts of the left frontal pole, frontal operculum, and inferior frontal gyrus, and overlapped with the territory of the frontal aslant tract. Finally, the map for goal-driven language selection encompassed the left frontal pole and the anterior cingulate cortex. We compare our findings with those from other neuropsychological samples, and conclude that the study of tumour patients offers evidence that complements that available from other populations.

Response: Sharpe, Goldsmith and Chalder fail to restore confidence in the PACE trial findings.

In a recent paper, we argued that the conclusions of the PACE trial of chronic fatigue syndrome are problematic because the pre-registered protocol was not adhered to. We showed that when the originally specific outcomes and analyses are used, the evidence for the effectiveness of CBT and graded exercise therapy is weak. In a companion paper to this article, Sharpe, Goldsmith and Chalder dismiss the concerns we raised and maintain that the original conclusions are robust. In this rejoinder, we clarify one misconception in their commentary, and address seven additional arguments they raise in defence of their conclusions. We conclude that none of these arguments is sufficient to justify digressing from the pre-registered trial protocol. Specifically, the PACE authors view the trial protocol as a preliminary plan, subject to honing and improvement as time progresses, whereas we view it as a contract that should not be broken except in extremely unusual circumstances. While the arguments presented by Sharpe and colleagues inspire some interesting reflections on the scientific process, they fail to restore confidence in the PACE trial's conclusions.

Rethinking the treatment of chronic fatigue syndrome-a reanalysis and evaluation of findings from a recent major trial of graded exercise and CBT.

BACKGROUND: The PACE trial was a well-powered randomised trial designed to examine the efficacy of graded exercise therapy (GET) and cognitive behavioural therapy (CBT) for chronic fatigue syndrome. Reports concluded that both treatments were moderately effective, each leading to recovery in over a fifth of patients. However, the reported analyses did not consistently follow the procedures set out in the published protocol, and it is unclear whether the conclusions are fully justified by the evidence. METHODS: Here, we present results based on the original protocol-specified procedures. Data from a recent Freedom of Information request enabled us to closely approximate these procedures. We also evaluate the conclusions from the trial as a whole. RESULTS: On the original protocol-specified primary outcome measure - overall improvement rates - there was a significant effect of treatment group. However, the groups receiving CBT or GET did not significantly outperform the Control group after correcting for the number of comparisons specified in the trial protocol. Also, rates of recovery were consistently low and not significantly different across treatment groups. Finally, on secondary measures, significant effects were almost entirely confined to self-report measures. These effects did not endure beyond two years. CONCLUSIONS: These findings raise serious concerns about the robustness of the claims made about the efficacy of CBT and GET. The modest treatment effects obtained on self-report measures in the PACE trial do not exceed what could be reasonably accounted for by participant reporting biases.

An evaluation of language in brain tumor patients using a new cognitively motivated testing protocol.

OBJECTIVE: To characterize the language impairments that occur in brain tumor patients using a cognitively oriented theoretical framework. METHOD: Forty-nine preoperative brain tumor patients completed a new testing protocol (the BLAST) which assesses 8 well documented, "core" cognitive skills required for language: auditory word recognition, accessing semantic knowledge, lexical selection, phonological encoding, verbal short-term memory, goal-driven language selection, verb retrieval, and articulatory-motor planning. Patients were unselected with respect to lesion location. RESULTS: A surprising 65% of patients scored below controls on at least 1 core skill. Patients with left temporal tumors, as a group, had lower scores than the remaining patients on phonological encoding, accessing semantic knowledge and verbal short-term memory (STM). Those with left frontal tumors had the lowest scores on articulatory-motor planning. These findings are broadly consistent with previous studies examining the anatomical substrates of our "core" cognitive processes. CONCLUSIONS: We conclude that selective impairments in key language skills are common in brain tumor patients, but many of these are not adequately assessed on conventional aphasia assessments. Our protocol may provide a useful resource for preoperative, postoperative and intraoperative language assessment in this population. (PsycINFO Database Record

Psychogenic Explanations of Physical Illness: Time to Examine the Evidence.

In some patients with chronic physical complaints, detailed examination fails to reveal a well-recognized underlying disease process. In this situation, the physician may suspect a psychological cause. In this review, we critically evaluated the evidence for this causal claim, focusing on complaints presenting as neurological disorders. There were four main conclusions. First, patients with these complaints frequently exhibit psychopathology but not consistently more often than patients with a comparable "organic" diagnosis, so a causal role cannot be inferred. Second, these patients report a high incidence of adverse life experiences, but again, there is insufficient evidence to indicate a causal role for any particular type of experience. Third, although psychogenic illnesses are believed to be more responsive to psychological interventions than comparable "organic" illnesses, there is currently no evidence to support this claim. Finally, recent evidence suggests that biological and physical factors play a much greater causal role in these illnesses than previously believed. We conclude that there is currently little evidential support for psychogenic theories of illness in the neurological domain. In future research, researchers need to take a wider view concerning the etiology of these illnesses.

What's in a sentence? The crucial role of lexical content in sentence production in nonfluent aphasia.

This study investigated the effect of lexical content on sentence production in nonfluent aphasia. Five participants with nonfluent aphasia, four with fluent aphasia, and eight controls were asked to describe pictured events in subject-verb-object sentences. Experiment 1 manipulated speed of lexical retrieval by varying the frequency of sentence nouns. Nonfluent participants' accuracy was consistently higher for sentences commencing with a high- than with a low-frequency subject noun, even when errors on those nouns were themselves excluded. This was not the case for the fluent participants. Experiment 2 manipulated the semantic relationship between subject and object nouns. The nonfluent participants produced sentences less accurately when they contained related than when they contained unrelated lexical items. The fluent participants exhibited the opposite trend. We propose that individuals with nonfluent aphasia are disproportionately reliant on activated conceptual-lexical representations to drive the sentence generation process, an idea we call the content drives structure (COST) hypothesis.

Semantic contributions to immediate serial recall: evidence from two contrasting aphasic individuals.

This paper examines the effect of semantic variables on serial recall in two contrasting aphasic cases and a group of controls. Experiment 1 manipulates word imageability and Experiment 2 manipulates semantic similarity. Controls not only showed better recall of imageable/semantically grouped lists, but under some conditions they also produced proportionately fewer phonological errors. These findings suggest that increasing the effectiveness of lexical/semantic support reduces reliance on phonological support. Consistent with this proposal, case TV, whose phonological impairment should increase his reliance on lexical/semantic support, produced abnormally low rates of phonological errors under some conditions. Conversely, case NP, who had a lexical/semantic impairment, produced abnormally high rates of phonological errors under some conditions. Analysis of serial recall curves in both aphasics and controls support the hypothesis that phonological processes are particularly critical for the recall of list-final items. However, there was no evidence that semantic support is especially crucial for list-initial recall. Controls did not exhibit stronger effects of semantic variables at list-initial position. Case NP (lexical/semantic impairment) performed disproportionately poorly on these items, but only under certain conditions.

Lexical competition for production in a case of nonfluent aphasia: converging evidence from four different tasks.

We report an individual with Broca's aphasia (J.H.M.), who exhibited powerful lexical context effects in word production tasks. In an adjective-noun production task (Experiment 1), J.H.M.'s production accuracy decreased as the number of adjectives in the phrase increased (e.g., curly hair vs. long curly hair). In a picture pair naming task (Experiment 2), J.H.M.'s naming accuracy was high, but her naming latencies were abnormally delayed when pairs were semantically related (e.g., goat and pig). This pattern was not observed for older controls. In a computerized Stroop task (Experiment 3), J.H.M.'s naming latencies were abnormally prolonged in the conflict condition, relative to a baseline colour naming task. This effect was far in excess of that for controls. Finally, in a blocked cyclic naming task (Experiment 4), J.H.M.'s accuracy was poorer and her latencies slower when the pictures were semantically related than when they were unrelated, and this effect built up across successive presentation cycles. It was far in excess of that exhibited by older controls. We propose that J.H.M.'s pattern of impairment across these four very different tasks suggests an impairment to a lexical control mechanism, whose normal function is to modulate the flow of activation throughout the lexical network, so as to minimize the competitive effects of nontarget lexical items.

Exploring the dynamics of aphasic word production using the picture-word interference task: a case study.

In this study, we use an auditory picture-word interference task to examine an anomic individual, NP. NP produced semantic errors in picture naming, but his comprehension was relatively well preserved. In the task, pictures to be named were accompanied by semantically, phonologically or unrelated distractors, presented at onsets ranging from -200ms (before target) to +400ms (after target). Naming latencies were measured. A group of 12 older controls showed semantic interference (slower latencies with semantic than with unrelated distractors), which was significant at -200ms, and steadily diminished across later onsets. In contrast, at 0ms, NP showed powerful semantic facilitation. There were no significant semantic effects at other onsets, but the trends, particularly at later onsets, were towards interference. Phonological effects for NP were in the same direction as for controls (facilitation) but were of greater magnitude. Indeed, NP showed a reliable facilitatory effect at 0ms (and trends at -200ms and +200ms), but a similar trend in controls failed to reach significance. Within recent models of this task, in which semantic facilitation effects are attributed to an early, pre-lexical semantic processing stage, NP's pattern indicates that semantic processing is abnormally prolonged. The phonological facilitation effects are also consistent with this interpretation. We discuss their implications and future applications of the task to aphasia.

Comparison of phonological and whole-word treatments for two contrasting cases of developmental dyslexia.

This study compared the effectiveness of two reading treatment programmes for two contrasting developmental dyslexics. W.B. demonstrated "pure" phonological dyslexia (deficient nonword reading but normal irregular-word reading) and N.S. "pure" surface dyslexia (the converse pattern). Both participants completed: (a) a phonological programme, which targeted the sublexical reading procedure through repeated exposure to word "families" with the same grapheme-phoneme correspondence (GPC; e.g., frail, raid, bait); and (b) a whole-word programme, which targeted the lexical reading procedure through tasks that emphasize whole-word visual analysis (e.g., speeded identification of visually degraded words). Both participants improved after training on the targeted words and/or GPCs. However, W.B. demonstrated reliable generalization only following the phonological programme and only in his reading of nonwords. In contrast, N.S. showed generalization across all types of word materials following both programmes. Although the whole-word programme (in particular the degraded-images technique) resulted in numerically greater improvement for N.S., this difference was not significant. Practical and theoretical implications of these results are discussed.

Contrasting effects of phonological priming in aphasic word production.

Two fluent aphasics, IG and GL, performed a phonological priming task in which they repeated an auditory prime then named a target picture. The two patients both had selective deficits in word production: they were at or near ceiling on lexical comprehension tasks, but were significantly impaired in picture naming. IG's naming errors included both semantic and phonemic paraphasias, as well as failures to respond, whereas GL's errors were mainly phonemic and formal paraphasias. The two patients responded very differently to phonological priming: IG's naming was facilitated (both accuracy and speed) only by begin-related primes (e.g. ferry-feather), whereas GL benefited significantly only from end-related primes (e.g. brother-feather), showing no more than a facilitatory trend with begin-related primes. We interpret these results within a two-stage model of word production, in which begin-related and end-related primes are said to operate at different stages. We then discuss implications for models of normal and aphasic word production in general and particularly with respect to sequential aspects of the phonological encoding process.

Origins of nonword phonological errors in aphasic picture naming.

A recent theory of lexical access in picture naming maintains that all nonword errors are generated during the retrieval of phonemic segments from the lexicon (Dell, Schwartz, Martin, Saffran, & Gagnon, 1997b). This theory is challenged by "dual origin" theories that postulate a second, post-lexical mechanism, whose disruption gives rise to "phonemic paraphasias" bearing close resemblance to the target. We tested the dual origin theory in a corpus of 457 nonword errors drawn from 18 subjects with fluent aphasia. The corpus was divided into two parts, based on degree of phonological overlap between error and target, and these parts were separately examined for proposed diagnostic characteristics of the postlexical error mechanism: serial order effects across the word, sensitivity to target length, and insensitivity to target frequency. Results did not support the dual origin theory but were consistent with a single, lexical origin account in which segment retrieval operates from left to right, rather than in parallel. Findings from this study also shed new light on how individual differences in the severity of the retrieval deficit modulate the expression of phonological errors in relation to target characteristics.

"Phonological" dysphasia: a cross-modal phonological impairment affecting repetition, production, and comprehension.

In this paper we describe an aphasic patient, MS, who is impaired across a wide range of auditory input processing and spoken word production tasks. MS's performance on all these tasks shows phonological features: (1) his performance is poorest on auditory tasks with a strong phonological component, such as phoneme discrimination, auditory lexical decision, and word-picture matching featuring phono-logically related distractors; and (2) in spoken word production tasks, his errors are mainly phonemic and formal paraphasias. MS's single word repetition is particularly poor and exhibits some of the features of deep dysphasia, including lexicality effects (MS is unable to repeat nonwords) and image-ability effects. However, unlike in deep dysphasia, there are no semantic errors. We show that MS's condition, although apparently heterogeneous when viewed from a functional architecture perspective, can be described quite elegantly within an interactive-activation framework by proposing a single abnormality-a pathologically fast rate of decay within phonological representations.

Syllables as units in speech production: Data from aphasia.

The syllable has received considerable empirical support as a unit of processing in speech perception, but its status in speech production remains unclear. Some researchers propose that syllables are individually represented and retrieved during phonological encoding (e.g., Dell, 1986; Ferrand, Segui, & Grainger, 1996; MacKay, 1987). We test this hypothesis by examining the influence of syllable frequency on the phonological errors of two aphasics. These individuals both had an impairment in phonological encoding, but appeared to differ in the precise locus of that impairment. They each read aloud and repeated 110 pairs of words matched for syllabic complexity, but differing in final syllable frequency. Lexical frequency was also controlled. Neither aphasic was more error-prone on low than on high frequency syllables (indeed, one showed a near-significant reverse effect), and neither showed a preference for more frequent syllables in their errors. These findings provide no support for the view that syllables are individually represented and accessed during phonological encoding.