Cross-modal plasticity refers to the concept that the cortex normally responsive to one sensory modality, when deprived of its usual input, becomes responsive to inputs from other sensory modalities. In blind subjects, the visual cortex processes somatosensory and auditory information. A recent functional imaging study found that verbal memory recall and verb generation significantly activated the primary visual cortex in early blind humans. The magnitude of occipital activation was positively correlated with subsequent performance on verbal memory and verb generation tasks. These results raised the untested hypothesis that the primary visual cortex may be the neural substrate mediating superior verbal memory performance in early blind individuals. The purpose of this protocol is to test this hypothesis. The first experiment will identify the magnitude of activation in cortical areas associated with successful verbal memory encoding and retrieval, and with verb generation, in blind individuals and sighted controls. The expected outcome is increased involvement of the visual cortex in the early blind group. In the second experiment, we will test the hypothesis that disruption of activity of the activated visual cortex (using TMS) will have deleterious effects on verbal memory encoding and verb generation in early blind subjects, but not in late blind subjects nor sighted controls. The TMS experiment is necessary to identify a cause-effect link between occipital activation and improved memory performance. Experiment 1: We plan to study early blind subjects, late blind subjects and sighted controls during encoding into and retrieval from episodic verbal memory, and during verb generation, using functional magnetic resonance imaging (fMRI). The primary outcome measure will be the number of voxels significantly activated in primary visual cortex in early blind subjects vs. late blind subjects and sighted controls. Experiment 2: We plan to apply rTMS over left primary visual cortex, left prefrontal cortex, and a control site during encoding of words into and retrieval of words from episodic memory (primary task), and during a verb generation task. Sighted volunteers, early blind and late blind subjects will be studied. The primary outcome measure will be performance on a memory test during rTMS applied to different sites in the different groups. This investigation is important because it can provide novel evidence on a hierarchically high function of the primary visual cortex in the blind.
ELIGIBILITY: Early Blind Subjects: Only compliant early blind subjects who have lost their vision before age 4 years due to diseases affecting the peripheral components of the visual system, i.e., blind subjects without any further neurological problems, and with normal MRI scans, will be selected. Late Blind Subjects: Only compliant late blind subjects who have lost their vision after age 4 years due to diseases affecting the peripheral components of the visual system, i.e., blind subjects without any further neurological problems, and with normal MRI scans, will be selected. Sighted Controls: Only compliant adult healthy volunteers with no history of neurological and psychiatric illness who are able to concentrate and to perform simple attentional tasks are eligible. INCLUSION CRITERIA: Blind Subjects: Early and late blind subjects (aged 18 or over) will be included in this protocol. Handedness will be assessed by the Edinburgh inventory scale. All experimental sessions will be studied on outpatient basis. Sighted Subjects: Healthy sighted (normal or corrected-to normal vision) matched in age, sex and level of education to the blind subjects. Handedness will be assessed by the Edinburgh inventory scale. EXCLUSION CRITERIA: Exclusion criteria for the study will be any current medical or surgical condition or psychiatric or neurological illness. Furthermore, any individual who is on medication with potential influence on nervous system function, who has a history of surgery with metallic implants or known history of metallic particles in the eye, cardiac pacemaker, intracardiac lines, neural stimulators, cochlear implants, pregnancy, or history of drug abuse, will be excluded from the study.