Cholinergic potentiation of visual perception and vision restoration in rodents and humans.

BACKGROUND: The cholinergic system is a potent neuromodulator system that plays a critical role in cortical plasticity, attention, and learning. Recently, it was found that boosting this system during perceptual learning robustly enhances sensory perception in rodents. In particular, pairing cholinergic activation with visual stimulation increases neuronal responses, cue detection ability, and long-term facilitation in the primary visual cortex. The mechanisms of cholinergic enhancement are closely linked to attentional processes, long-term potentiation, and modulation of the excitatory/inhibitory balance. Some studies currently examine this effect in humans. OBJECTIVE: The present article reviews the research from our laboratory, examining whether potentiating the central cholinergic system could help visual perception and restoration. METHODS: Electrophysiological or pharmacological enhancement of the cholinergic system are administered during a visual training. Electrophysiological responses and perceptual learning performance are investigated before and after the training in rats and humans. This approach's ability to restore visual capacities following a visual deficit induced by a partial optic nerve crush is also investigated in rats. RESULTS: The coupling of visual training to cholinergic stimulation improved visual discrimination and visual acuity in rats, and improved residual vision after a deficit. These changes were due to muscarinic and nicotinic transmissions and were associated with a functional improvement of evoked potentials. In humans, potentiation of cholinergic transmission with 5 mg of donepezil showed improved learning and ocular dominance plasticity, although this treatment was ineffective in augmenting the perceptual threshold and electroencephalography. CONCLUSIONS: Potential therapeutic outcomes ought to facilitate vision restoration using commercially available cholinergic agents combined with visual stimulation in order to prevent irreversible vision loss in patients. This approach has the potential to help a large population of visually impaired individuals.

Differential engagement of attention and visual working memory in the representation and evaluation of the number of relevant targets and their spatial relations: Evidence from the N2pc and SPCN.

We examined the role of attention and visual working memory in the evaluation of the number of target stimuli as well as their relative spatial position using the N2pc and the SPCN. Participants performed two tasks: a simple counting task in which they had to determine if a visual display contained one or two coloured items among grey fillers and one in which they had to identify a specific relation between two coloured items. The same stimuli were used for both tasks. Each task was designed to permit an easier evaluation of either the same-coloured or differently-coloured stimuli. We predicted a greater involvement of attention and visual working memory for more difficult stimulus-task pairings. The results confirmed these predictions and suggest that visuospatial configurations that require more time to evaluate induce a greater (and presumably longer) involvement of attention and visual working memory.

Optimal measurements of hemodynamic response latency in fNIRS using the jackknife approach.

Functional near-infrared spectroscopy (fNIRS) permits measurements of changes in the concentration of oxygenated and deoxygenated hemoglobin, typically with a higher sampling rate than with other imaging methods based on the hemodynamic response. We examined the potential of the fNIRS technique to estimate variations in the latency of hemodynamic responses to experimental events and sought optimal methods to maximize the reliability and reproducibility of latency effects. We used Monte Carlo simulations using subsamples of real fNIRS measures to estimate the statistical power of different approaches (such as fixed threshold, percent of peak, fractional-area latency, for both individual-subject estimates and estimates from jackknife averages) to detect a known simulated latency shift. The simulations used measures of hemodynamic responses in the temporal lobe from two groups of young adult participants who listened to auditory stimuli, one with a blocked presentation design and one with an event-related design. We estimated the relative sensitivity of different latency measures and approaches to the measurement of latency effects of different magnitudes using realistic noise and signal-to-noise characteristics. In general, the jackknife approach provided the greatest statistical power to detect a known latency shift, without inflation of Type I error.

Contribution of NIRS to the study of prefrontal cortex for verbal fluency in aging.

Healthy aging is characterized by a number of changes on brain structure and function. Several neuroimaging studies have shown an age-related reduction in hemispheric asymmetry on various cognitive tasks, a phenomenon captured by Cabeza (2002) in the Hemispheric Asymmetry Reduction in Older Adults (HAROLD) model. Although this phenomenon is supported by a range of neuroimaging data on memory and inhibitory processes, there is little evidence concerning changes in hemispheric asymmetry for language processing, and particularly word retrieval, which is assessed with verbal fluency task (VFT). This study aimed to investigate the age-related changes in cerebral oxygenation in the prefrontal cortex for both letter and category VFT, varying the complexity of the criteria (i.e., degree of productivity) and using near-infrared spectroscopy (NIRS). Sixteen younger and 16 older adults participated in this study. For both VF conditions, participants were instructed to pronounce as many nouns as possible as a function of high-productivity (e.g., "animals" or "L") or low-productivity (e.g., "flowers" or "V") criteria. Behavioral data (i.e., accuracy responses) showed comparable performance in younger and older adults for both VF conditions. However, NIRS data showed more reduced activation (i.e., significantly reduced increase in [O(2)Hb] and reduced decrease in [HHb]) in older than younger adults for both VFT. In addition, a bilateral effect was found for both groups, suggesting that VFT requires both executive and language functions. The results are discussed in the context of the current theories of aging.