1. To identify patterns of brain activation during phonetic perception in individual stroke patients using fMRI, as the basis for Studies 1 & 2;
2. To determine the effectiveness of TMS paired with behavioral treatment for phonetic perception impairment versus the behavioral treatment alone (Study 1);
3. To evaluate changes in brain activation during phonetic perception in individual stroke patients pre-treatment versus post-treatment with TMS (Study 2).
Our hypothesis is that TMS used in the right way can be used to enhance or facilitate adaptive neural plasticity. Contingent pairing of TMS targeted at an a priori-defined specific cortical region with a desired outcome (correct response) should upregulate this region of cortex in association with the existing network, effectively augmenting this network. Repeating this contingent coactivation will further strengthen this linkage, which will theoretically lead to a functional gain. Rather than stimulate the same anatomical site in all subjects, we hypothesize that using the patient's own brain activation pattern evoked by correct performance gives us the best chance to obtain an effect. MRI-lucent skin markers on the scalp would serve to coregister anatomy between TMS and fMRI, already done routinely clinically.
Eighteen aphasics, well studied by neuropsychological methods in the chronic phase of stroke recovery (>6 months post stroke), i.e. have reached a plateau, will be studied. We will use aphasics impaired on speech perception since, using fMRI, we have defined a network in normal subjects used in phonetic perception (Benson R, et al. Brain & Language:2001). The trained task will be a phonetic judgment task using standardized test items. Event-related fMRI of correct trials will be compared with incorrect trials in order to determine which of the four regions previously identified with phonetic perception shows the greatest positive correlation with performance. Those trials which the subject is found to reliably perform correctly will serve as the events to which TMS will be synchronously timed.
Nine subjects will undergo training on speech perception tasks in conjunction with TMS applied synchronously with phonetic judgment three times per week for 6 weeks. The other 9 Ss will receive identical training, but with sham TMS rather than active TMS. Both the therapist and patient will be blinded to which type of TMS is used. FMRI will be done at baseline, within 1 week of concluding the 6 week rehabilitation period, and 3 weeks following conclusion of rehabilitation. Psycholinguistic assessment will use a standard aphasia battery at every treatment, and at the conclusion of the treatment period a detailed assessment of the speech recognition, repetition, and naming ability will be done to evaluate interval change in trained and untrained linguistic functions. Analysis of brain images will emphasize changes in brain activation, primarily in pre-defined speech perception areas, within subject scans over time. Both regional and network-wise approaches will be used after stereotactic spatial normalization of each brain image.
Significance: Currently, recovery following cortical stroke is variable but accounts for major disability in western societies where stroke occurrence is high. Aphasic stroke results in losses across multiple spheres, including social and occupational, with conventional methods of speech/language therapy having limited efficacy. Electromagnetic stimulation with TMS has been recently used to effectively and safely treat depression, dystonia, and epilepsy (other uses are being explored), and in the last year has been found to improve performance on cognitive and language tasks. Our intention is to attempt to use TMS applied to a known speech perception network to induce functional plasticity in aphasic patients with speech perception deficits.
Recently established principles governing cortical remapping described in the body of this proposal form the underlying conceptual model upon which the proposed experiments are based. With TMS and fMRI—i.e., to experimentally manipulate the network (via TMS) while monitoring the networks s response to the manipulation (via fMRI)—we will be ideally situated to push the limits of adaptive cortical plasticity. While we acknowledge that much remains to be learned, we believe that the research proposed herein is a logical application of principle and technology that should result in important new principles and has the potential to give rise to therapies based on a new paradigm in the treatment of cognitive and brain disorders.