Dopaminergic therapy in aphasia

Background: The dopaminergic system is involved in a wide range of cognitive functions including motor control, reward, memory, attention, problem-solving and learning. This has stimulated interest in investigating the potential of dopaminergic drugs as cognitive enhancers in aphasic patients. / Aim: To discuss the evidence for the use of dopaminergic agents in patients with aphasia. Levodopa (L-dopa) and the dopamine agonist bromocriptine are the two drugs that have been trialled to date. We discuss, in some detail, the 15 studies that have been published on this topic from the first case report in 1988 to the present (2012), and assess the evidence from each. / Main contribution: In addition to summarising the effectiveness of the drugs that have been tried, we examine the possible cognitive mechanisms by which dopaminergic drugs may act on language function and aphasia recovery. Given the wide range of dopaminergic drugs, it is surprising that such a narrow range has been trialled in aphasic patients. Important lessons are to be learned from published studies and we discuss optimal trial designs to help guide future work. / Conclusions: The evidence for the efficacy of dopaminergic agents in aphasia therapy is mixed. Further trials with better tolerated agents are required. Optimal trial designs with appropriate control groups or blocks should be used. The mechanism of action is unclear, but at the cognitive level the evidence points towards either (re)learning of word-forms or their improved retrieval

Using functional imaging to understand therapeutic effects in poststroke aphasia

PURPOSE OF REVIEW: The evidence base for the treatment of poststroke aphasia continues to grow, so too does interest in the neural mechanisms that underlie these therapy-driven improvements. Although the majority of patients respond to therapy, not all of those who do improve do so in a predictable way. Here, we review 17 of the most recent articles that have attempted to deal with this important question, dividing them into those that target speech perception and production. RECENT FINDINGS: There are many methodological differences between the studies, but some neuroimaging patterns have emerged: whether the in-scanner language task is speech perception or production, left hemisphere fronto-temporal cortex is often activated/correlated with language improvement and; right inferior frontal gyrus is frequently identified although what this represents is still hotly contested. We are concerned that many studies are not well controlled making it difficult to ascribe neuroimaging changes directly to the therapeutic intervention. SUMMARY: Encouragingly, there are many more functional imaging studies in this challenging area of research. Behaviour, either alone or paired with structural imaging data, only goes part way in explaining aphasic patients’ responses to therapy. An important emerging theme is exploring the role that nonlanguage cognitive processes play in aphasia recovery

The cost to see the Wizard: buy-ins and trade-offs in neurological rehabilitation

This scientific commentary refers to ‘A decision-neuroscientific intervention to improve cognitive recovery after stroke’ by Studer et al. (doi:10.1093/brain/awab128)

Facilitating text reading in posterior cortical atrophy

Objective We report 1) the first quantitative investigation of text reading in posterior cortical atrophy (PCA); and 2) the effects of two novel software-based reading aids that result in dramatic improvements in PCA patients' reading ability. Methods Reading performance, eye movements and fixations were assessed in PCA and typical Alzheimer’s disease (tAD) patients and healthy controls (Experiment 1). Two reading aids (single- and double-word) were evaluated based on the notion that reducing the spatial and oculomotor demands of text reading might support reading in PCA (Experiment 2). Results PCA patients’ mean reading accuracy was significantly worse (57%) compared to both tAD patients (98%) and healthy controls (99%); spatial aspects of passages were the primary determinants of text reading ability in PCA. Both aids led to considerable gains in reading accuracy (PCA mean reading accuracy: single-word reading aid = 96%; individual patient improvement range: 6%-270%) and self-rated measures of reading. Data suggest a greater efficiency of PCA patients’ fixations and eye movements under the single-word reading aid. Conclusions These findings demonstrate how neurological characterisation of a neurodegenerative syndrome (PCA) and detailed cognitive analysis of an important everyday skill (reading) can combine to yield aids capable of supporting important everyday functional abilities. Classification of evidence This study provides Class III evidence that for patients with posterior cortical atrophy, two software-based reading aids (single-word and double-word) improve reading accuracy

Between Thought and Expression, a Magnetoencephalography Study of the "Tip-of-the-Tongue" Phenomenon

“Tip-of-the-tongue” (TOT) is the phenomenon associated with the inaccessibility of a known word from memory. It is universally experienced, increases in frequency with age, and is most common for proper nouns. It is a good model for the symptom of anomia experienced much more frequently by some aphasic patients following brain injury. Here, we induced the TOT state in older participants while they underwent brain scanning with magnetoencephalography to investigate the changes in oscillatory brain activity associated with failed retrieval of known words. Using confrontation naming of pictures of celebrities, we successfully induced the TOT state in 29% of trials and contrasted it with two other states: “Know” where the participants both correctly recognized the celebrity's face and retrieved their name and “Don't Know” when the participants did not recognize the celebrity. We wished to test Levelt's influential model of speech output by carrying out two analyses, one epoching the data to the point in time when the picture was displayed and the other looking back in time from when the participants first articulated their responses. Our main findings supported the components of Levelt's model, but not their serial activation over time as both semantic and motor areas were identified in both analyses. We also found enduring decreases in the alpha frequency band in the left ventral temporal region during the TOT state, suggesting ongoing semantic search. Finally, we identified reduced beta power in classical peri-sylvian language areas for the TOT condition, suggesting that brain regions that encode linguistic memories are also involved in their attempted retrieval

Can fully automated detection of corticospinal tract damage be used in stroke patients?

We compared manual infarct definition, which is time-consuming and open to bias, with an automated abnormal tissue detection method in measuring corticospinal tract-infarct overlap volumes in chronic stroke patients to help predict motor outcome

Avatar therapy for persecutory auditory hallucinations: What is it and how does it work?

We have developed a novel therapy based on a computer program, which enables the patient to create an avatar of the entity, human or non-human, which they believe is persecuting them. The therapist encourages the patient to enter into a dialogue with their avatar, and is able to use the program to change the avatar so that it comes under the patient's control over the course of six 30-min sessions and alters from being abusive to becoming friendly and supportive. The therapy was evaluated in a randomised controlled trial with a partial crossover design. One group went straight into the therapy arm: "immediate therapy". The other continued with standard clinical care for 7 weeks then crossed over into Avatar therapy: "delayed therapy". There was a significant reduction in the frequency and intensity of the voices and in their omnipotence and malevolence. Several individuals had a dramatic response, their voices ceasing completely after a few sessions of the therapy. The average effect size of the therapy was 0.8. We discuss the possible psychological mechanisms for the success of Avatar therapy and the implications for the origins of persecutory voices. © 2013 Copyright Taylor and Francis Group, LLC

Category-selective deficits are the exception and not the rule: Evidence from a case-series of 64 patients with ventral occipito-temporal cortex damage

The organisational principles of the visual ventral stream are still highly debated, particularly the relative association/dissociation between word and face recognition and the degree of lateralisation of the underlying processes. Reports of dissociations between word and face recognition stem from single case-studies of category selective impairments, and neuroimaging investigations of healthy participants. Despite the historical reliance on single case-studies, more recent group studies have highlighted a greater commonality between word and face recognition. Studying individual patients with rare selective deficits misses (a) important variability between patients, (b) systematic associations between task performance, and (c) patients with mild, severe and/or non-selective impairments; meaning that the full spectrum of deficits is unknown. The Back of the Brain project assessed the range and specificity of visual perceptual impairment in 64 patients with posterior cerebral artery stroke recruited based on lesion localization and not behavioural performance. Word, object, and face processing were measured with comparable tests across different levels of processing to investigate associations and dissociations across domains. We present two complementary analyses of the extensive behavioural battery: (1) a data-driven analysis of the whole patient group, and (2) a single-subject case-series analysis testing for deficits and dissociations in each individual patient. In both analyses, the general organisational principle was of associations between words, objects, and faces even following unilateral lesions. The majority of patients either showed deficits across all domains or in no domain, suggesting a spectrum of visuo-perceptual deficits post stroke. Dissociations were observed, but they were the exception and not the rule: Category-selective impairments were found in only a minority of patients, all of whom showed disproportionate deficits for words. Interestingly, such selective word impairments were found following both left and right hemisphere lesions. This large-scale investigation of posterior cerebral artery stroke patients highlights the bilateral representation of visual perceptual function

Generative Embedding for Model-Based Classification of fMRI Data

Decoding models, such as those underlying multivariate classification algorithms, have been increasingly used to infer cognitive or clinical brain states from measures of brain activity obtained by functional magnetic resonance imaging (fMRI). The practicality of current classifiers, however, is restricted by two major challenges. First, due to the high data dimensionality and low sample size, algorithms struggle to separate informative from uninformative features, resulting in poor generalization performance. Second, popular discriminative methods such as support vector machines (SVMs) rarely afford mechanistic interpretability. In this paper, we address these issues by proposing a novel generative-embedding approach that incorporates neurobiologically interpretable generative models into discriminative classifiers. Our approach extends previous work on trial-by-trial classification for electrophysiological recordings to subject-by-subject classification for fMRI and offers two key advantages over conventional methods: it may provide more accurate predictions by exploiting discriminative information encoded in 'hidden' physiological quantities such as synaptic connection strengths; and it affords mechanistic interpretability of clinical classifications. Here, we introduce generative embedding for fMRI using a combination of dynamic causal models (DCMs) and SVMs. We propose a general procedure of DCM-based generative embedding for subject-wise classification, provide a concrete implementation, and suggest good-practice guidelines for unbiased application of generative embedding in the context of fMRI. We illustrate the utility of our approach by a clinical example in which we classify moderately aphasic patients and healthy controls using a DCM of thalamo-temporal regions during speech processing. Generative embedding achieves a near-perfect balanced classification accuracy of 98% and significantly outperforms conventional activation-based and correlation-based methods. This example demonstrates how disease states can be detected with very high accuracy and, at the same time, be interpreted mechanistically in terms of abnormalities in connectivity. We envisage that future applications of generative embedding may provide crucial advances in dissecting spectrum disorders into physiologically more well-defined subgroups