Using fMRI and Behavioural Measures to Investigate Rehabilitation in Post-Stroke Aphasic Deficits

In this thesis I investigated whether an intensive computerised, home-based therapy programme could improve phonological discrimination ability in 19 patients with chronic post-stroke aphasia. One skill specifically targeted by the treatment demonstrated an improvement due to the therapy. However, this improvement did not generalise to untreated items, and was only effective for participants without a lesion involving the frontal lobe, indicating a potentially important role for this region in determining outcome of aphasia therapy. Complementary functional imaging studies investigated activity in domain-general and domain-specific networks in both patients and healthy volunteers during listening and repeating simple sentences. One important consideration when comparing a patient group with a healthy population is the difference in task difficulty encountered by the two groups. Increased cognitive effort can be expected to increase activity in domain-general networks. I minimised the effect of this confound by manipulating task difficulty for the healthy volunteers to reduce their behavioural performance so that it was comparable to that of the patients. By this means I demonstrated that the activation patterns in domain-general regions were very similar in the two groups. Region-of-interest analysis demonstrated that activity within a domain-general network, the salience network, predicted residual language function in the patients with aphasia, even after accounting for lesion volume and their chronological age. I drew two broad conclusions from these studies. First, that computer-based rehabilitation can improve disordered phonological discrimination in chronic aphasia, but that lesion distribution may influence the response to this training. Second, that the ability to activate domain-general cognitive control regions influences outcome in aphasia. This allows me to propose that in future work, therapeutic strategies, pharmacological or behavioural, targeting domain-general brain systems, may benefit aphasic stroke rehabilitation.Open Acces

Efficacy of spoken word comprehension therapy in patients with chronic aphasia: a cross-over randomised controlled trial with structural imaging

Objective: The efficacy of spoken language comprehension therapies for persons with aphasia remains equivocal. We investigated the efficacy of a self-led therapy app, ‘Listen-In’, and examined the relation between brain structure and therapy response. Methods: A cross-over randomised repeated measures trial with five testing time points (12-week intervals), conducted at the university or participants' homes, captured baseline (T1), therapy (T2-T4) and maintenance (T5) effects. Participants with chronic poststroke aphasia and spoken language comprehension impairments completed consecutive Listen-In and standard care blocks (both 12 weeks with order randomised). Repeated measures analyses of variance compared change in spoken language comprehension on two co-primary outcomes over therapy versus standard care. Three structural MRI scans (T2-T4) for each participant (subgroup, n=25) were analysed using cross-sectional and longitudinal voxel-based morphometry. Results: Thirty-five participants completed, on average, 85 hours (IQR=70–100) of Listen-In (therapy first, n=18). The first study-specific co-primary outcome (Auditory Comprehension Test (ACT)) showed large and significant improvements for trained spoken words over therapy versus standard care (11%, Cohen’s d=1.12). Gains were largely maintained at 12 and 24 weeks. There were no therapy effects on the second standardised co-primary outcome (Comprehensive Aphasia Test: Spoken Words and Sentences). Change on ACT trained words was associated with volume of pretherapy right hemisphere white matter and post-therapy grey matter tissue density changes in bilateral temporal lobes. Conclusions: Individuals with chronic aphasia can improve their spoken word comprehension many years after stroke. Results contribute to hemispheric debates implicating the right hemisphere in therapy-driven language recovery. Listen-In will soon be available on GooglePlay. Trial registration number: NCT02540889

The Contribution of the Parietal Lobes to Speaking and Writing

The left parietal lobe has been proposed as a major language area. However, parietal cortical function is more usually considered in terms of the control of actions, contributing both to attention and cross-modal integration of external and reafferent sensory cues. We used positron emission tomography to study normal subjects while they overtly generated narratives, both spoken and written. The purpose was to identify the parietal contribution to the modality-specific sensorimotor control of communication, separate from amodal linguistic and memory processes involved in generating a narrative. The majority of left and right parietal activity was associated with the execution of writing under visual and somatosensory control irrespective of whether the output was a narrative or repetitive reproduction of a single grapheme. In contrast, action-related parietal activity during speech production was confined to primary somatosensory cortex. The only parietal area with a pattern of activity compatible with an amodal central role in communication was the ventral part of the left angular gyrus (AG). The results of this study indicate that the cognitive processing of language within the parietal lobe is confined to the AG and that the major contribution of parietal cortex to communication is in the sensorimotor control of writing

Language and language disorders: neuroscience to clinical practice

Language disorders are common in neurological practice but their accurate recognition and description can be challenging. In this review, we summarise the major landmarks in the understanding of language disorders and the organisation of language in the brain. We describe approaches to assessing language disorders at the bedside or in the clinic as well as the treatment and rehabilitation of aphasia. Finally, we describe how the field of neuroscience is providing new computational and neuroscientific approaches to study the mechanisms of recovery and rehabilitation of aphasia

Task-induced brain activity in aphasic stroke patients: what is driving recovery?

The estimated prevalence of aphasia in the UK and the USA is 250 000 and 1 000 000, respectively. The commonest aetiology is stroke. The impairment may improve with behavioural therapy, and trials using cortical stimulation or pharmacotherapy are undergoing proof-of-principle investigation, but with mixed results. Aphasia is a heterogeneous syndrome, and the simple classifications according to the Broca-Wernicke-Lichtheim model inadequately describe the diverse communication difficulties with which patients may present. Greater knowledge of how intact neural networks promote recovery after aphasic stroke, either spontaneously or in response to interventions, will result in clearer hypotheses about how to improve the treatment of aphasia. Twenty-five years ago, a pioneering study on healthy participants heralded the introduction of functional neuroimaging to the study of mechanisms of recovery from aphasia. Over the ensuing decades, such studies have been interpreted as supporting one of three hypotheses, which are not mutually exclusive. The first two predate the introduction of functional neuroimaging: that recovery is the consequence of the reconstitution of domain-specific language systems in tissue around the lesion (the ‘perilesional’ hypothesis), or by homotopic cortex in the contralateral hemisphere (the ‘laterality-shift’ hypothesis). The third is that loss of transcallosal inhibition to contralateral homotopic cortex hinders recovery (the ‘disinhibition’ hypothesis). These different hypotheses at times give conflicting views about rehabilitative intervention; for example, should one attempt to activate or inhibit a contralateral homotopic region with cortical stimulation techniques to promote recovery? This review proposes that although the functional imaging data are statistically valid in most cases, their interpretation has often favoured one explanation while ignoring plausible alternatives. In our view, this is particularly evident when recovery is attributed to activity in ‘language networks’ occupying sites not observed in healthy participants. In this review we will argue that much of the distribution of what has often been interpreted as language-specific activity, particularly in midline and contralateral cortical regions, is an upregulation of activity in intact domain-general systems for cognitive control and attention, responding in a task-dependent manner to the increased ‘effort’ when damaged downstream domain-specific language networks are impaired. We further propose that it is an inability fully to activate these systems that may result in sub optimal recovery in some patients. Interpretation of the data in terms of activity in domain-general networks affords insights into novel approaches to rehabilitation

Language and language disorders: neuroscience to clinical practice

Language disorders are common in neurological practice but their accurate recognition and description can be challenging. In this review, we summarise the major landmarks in the understanding of language disorders and the organisation of language in the brain. We describe approaches to assessing language disorders at the bedside or in the clinic as well as the treatment and rehabilitation of aphasia. Finally, we describe how the field of neuroscience is providing new computational and neuroscientific approaches to study the mechanisms of recovery and rehabilitation of aphasia

A step forward for mirror neurons? Investigating the functional link between action execution and action observation in limb apraxia

Increasing evidence suggests that action execution and action observation are encoded by the same brain regions. This renders motor events central to the question of self and nonself discrimination (Georgieff and Jeannerod, 1998). In humans, it is widely assumed that mirror neurons link action observation and action execution networks. These neurons respond during action execution and action observation and have been found in macaque premotor and inferior parietal cortices (di Pellegrino et al., 1992; Rizzolatti et al., 1996). The evidence for human mirror neurons is far from conclusive. Nevertheless, the presence of a general action “mirroring” system is well established (Dinstein et al., 2008). Human brains encode action execution and action observation in a remarkably similar way (Rizzolatti and Craighero, 2004), but what purpose this system serves remains unclear. It has been proposed that it is involved in action recognition, action imitation, understanding of action and emotion, imitation, and the developmental and evolutionary acquisition of language. However, it is possible that coupling of the two networks is a functionless consequence of motor development. For example, during development, Hebbian coupling may link neurons that fire during action execution to those that respond during action perception

Intersubject variability in spoken verb production: Effects of hierarchy and transitivity

In two experiments employing the picture-word interference (PWI) paradigm, we explored how a verb’s hierarchy and transitivity influences its retrieval during spoken production. Experiment 1 involved transitive (i.e. object-oriented, e.g. eat) action pictures accompanied by a to-be-ignored distractor word that was either a related coordinate (‘drink’) or troponym (‘devour’), while Experiment 2 employed intransitive (e.g. walk) stimuli. Assuming these relationships operate similarly for verbs and object nouns, we expected to observe faster naming times for troponyms, and slower naming times for coordinates. Conventional group-level analyses of the null average hypothesis revealed no significant effects in either experiment. However, analyses of the global null hypothesis revealed significant interindividual variability for troponym distractors in Experiment 1, with a similar trend in Experiment 2. These results indicate verbs may have a different conceptual-lexical organisation to object nouns in the mental lexicon, less constrained by hierarchical categories, with their processing more influenced by subject-specific variables