This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This protocol qualifies for expedited status because it involves only non-invasive neuropsychological tests and fMRI studies at 1.5T field strength. Episodic memory - memory for contextually-specific information - is crucially dependent upon the hippocampal formation and adjacent medial temporal cortex (MTL). These bilateral structures are required both for the acquisition of episodic information and for its retrieval. Functional neuroimaging studies have demonstrated that the successful retrieval of episodic information involves activation not only of the hippocampal formation, but also a widespread network of cortical regions including medial and lateral parietal cortex, and anterior, infero- and dorsolateral prefrontal cortex. It is assumed that this is a consequence of the cortico-hippocampal interactions thought to underlie successful episodic retrieval. Recent event-related fMRI studies - which permit the neural activity elicited by specific classes of experimental stimuli to be identified - have demonstrated that in many circumstances (including the experimental procedure described below), retrieval-related activity is strongly lateralized to the left hemisphere. Temporal lobe epilepsy patients who have undergone unilateral temporal lobe resection (UTLR - either anteromedial temporal lobectomy or selective amygdalohippocampectomy) for treatment of their epilepsy are unique in that the functioning of the medial temporal/hippocampal system must be unilateral (i.e. confined to the unoperated hemisphere). What is the impact of removing one MTL on the cortical network involved in memory encoding and retrieval? Since connections between the MTL and neocortex are exclusively ipsilateral, one possibility is that cortical memory function is confined to the unoperated hemisphere. If this is the case, then in circumstances where these functions are mediated by the operated (left) hemisphere in healthy controls, memory-related cortical activity should be observed in the opposite (right) hemisphere of left-sided UTLR patients. Alternatively, it may be that the remaining right MTL maintains connectivity with the same left hemisphere cortical regions as those activated in healthy controls. In the absence of direct anatomic connections between MTL and contralateral neocortex, information must flow to and from the MTL via ipsilateral cortical regions prior to transfer via the corpus callosum to contralateral cortex. Under this scenario, additional cortical activity should be present in patients relative to controls in the unoperated hemisphere, along with a common pattern of cortical activity in the operated hemisphere (discounting any regions, of course, that were compromised by the surgical intervention).
The aim of the proposed study is to evaluate these two possibilities with an experimental procedure already demonstrated to produce strongly left-lateralized retrieval-related cortical activity in healthy adults. Thus, the key contrast will be between healthy controls and patients who have undergone left UTLR for relief of intractable epilepsy. A group of right UTLR patients will also be studied, so as to permit dissociation between inter-group differences related to side of pathology, and those due to the general effects epilepsy and epilepsy surgery (which are of no interest in the present context).
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