Mechanisms for the recovery of aphasia following stroke. A positron emission tomography study

Language disorders following stroke are common and are a major source of distress and disability. Most patients show some recovery with time implying the potential for neuronal plasticity within the brain for recovery of language. The mechanisms underlying recovery are poorly understood, making strategies for speech therapy and further investigation of potential therapeutic agents difficult. These studies were designed to explore the cortical re-organisation which underlies at least some language recovery using positron emission tomography (PET). With the rapid developments in PET technology and advances in image data processing it is now well established that language tasks can be studied in terms of responses within brain regions, and interactions between regions. The results can be interpreted with reference to neuropsychological theory and models. Many language activation studies have been performed in the normal brain. The studies reported here concentrated on one behavioural task - the verbal fluency task - the strategy being to compare patterns of activation in normal subjects with those in recovered aphasic patients performing the same fluency task. In the first part of this thesis, a detailed PET study of a verb retrieval task was made using different control tasks in normal volunteers. The results show that this task engages a widespread network of regions, predominantly in the left hemisphere i.e. the dorsolateral temporal cortex, the inferolateral temporal cortex and inferior parietal cortex, an extensive area of the dorsolateral prefrontal cortex (LDLPFC), the anterior cingulate and the supplementary motor area (SMA). The experiments using different control tasks suggest that the dorsolateral temporal cortex is involved with auditory and lexical processing of the stimulus nouns and it is demonstrated that observation of an activation in this region is dependent on the particular control task used with the retrieval task. This explains discrepancies between results of previous PET verbal fluency studies. A novel finding in these studies was that the left inferolateral temporal cortex and inferior parietal cortex are specifically associated with the retrieval of words from semantic memory. These findings are in accordance with recent work with Alzheimer's patients and cortical stimulation studies. The functional role of the extensive LDLPFC activation is probably multifactorial and includes working memory, monitoring, choosing between conflicting responses and prearticulatory processes. The activation of the anterior cingulate is consistent with it's postulated role in attention and the activation of the SMA is suggested to be in readiness to articulate. There was no word class effect between noun retrieval and verb retrieval. A cohort of aphasic stroke patients were recruited for these studies and tested using a specifically designed test battery at three month intervals following stroke onset. Only those recovering sufficiently well to be able to perform the verb retrieval task were scanned. These patients had both MRI and PET scans, the results being co-registered to show each individual's blood flow data with their MRI scan. These studies were some of the first to demonstrate the successful use of this method for single subject data. The results did not show a contralateral shift in activation of the inferolateral temporal cortex but demonstrated left temporal peri-lesional activity, implying redundancy of function. Some patients showed increased activation of the right dorsolateral temporal cortex, suggesting that there may be right hemisphere capacity for augmented auditory, lexical and semantic processing of the heard nouns. Whether these effects represent inter-individual variability is not yet known. The activation of the DLPFC was very variable between patients and a general finding was that of increased right prefrontal activity. This may represent increased load on attentional networks as the patients found the task much more difficult than the normal subjects. (author)