Our purpose was to determine if sensitization to nicotine could be assessed using functional magnetic resonance imaging (fMRI) with BOLD contrast. Sensitization describes a phenomenon whereby subsequent doses of a drug produce greater responses than the initial dose. Robust locomotor sensitization was demonstrated in adult male Sprague-Dawley rats by the daily administration of nicotine 0.4 mg/kg over 5 days. In parallel experiments, brain activity was monitored using fMRI in animals receiving their first dose (acute) or fifth dose of nicotine (sensitized) and appropriate saline controls. Compared to the acute nicotine animals, brain activity in the sensitized animals demonstrated prolonged BOLD activation in response to nicotine in the hippocampus, nucleus accumbens, prefrontal cortex, ventral pallidum and ventral tegmentum, and more intense peak activation in the hippocampus, prefrontal cortex and ventral tegmentum. In addition, sensitization was associated with a relative decrease in activation in the anterior cingulate gyrus. Furthermore, despite the rich endowment of nicotinic receptors in the visual cortex there was no change in activation with sensitization, thus establishing the specificity of the observed pattern of regional activation and inhibition. Taken together, the current studies support the premise that nicotine sensitization is accompanied by changes in brain activation including a sensitized BOLD response in the extended limbic system that may subserve the process of dependence.

Neurological findings suggest that the human striate cortex (V1) is an indispensable component of a neural substratum subserving static achromatic form perception in its own right and not simply as a central distributor of retinally derived information to extrastriate visual areas. This view is further supported by physiological evidence in primates that the finest-grained conjoined representation of spatial detail and retinotopic localization that underlies phenomenal visual experience for local brightness discriminations is selectively represented at cortical levels by the activity of certain neurons in V1. However, at first glance, support for these ideas would appear to be undermined by incontrovertible neurological evidence (visual hemineglect and the simultanagnosias) and recent psychophysical results on 'crowding' that confirm that activation of neurons in V1 may, at times, be insufficient to generate a percept. Moreover, a recent proposal suggests that neural correlates of visual awareness must project directly to those in executive space, thus automatically excluding V1 from a related perceptual space because V1 lacks such direct projections. Both sets of concerns are, however, resolved within the context of adaptive resonance theories. Recursive loops, linking the dorsal lateral geniculate nucleus (LGN) through successive cortical visual areas to the temporal lobe by means of a series of ascending and descending pathways, provide a neuronal substratum at each level within a modular framework for mutually consistent descriptions of sensory data. At steady state, such networks obviate the necessity that neural correlates of visual experience project directly to those in executive space because a neural phenomenal perceptual space subserving form vision is continuously updated by information from an object recognition space equivalent to that destined to reach executive space. Within this framework, activity in V1 may engender percepts that accompany figure-ground segregations only when dynamic incongruities are resolved both within and between ascending and descending streams. Synchronous neuronal activity on a short timescale within and across cortical areas, proposed and sometimes observed as perceptual correlates, may also serve as a marker that a steady state has been achieved, which, in turn, may be a requirement for the longer time constants that accompany the emergence and stability of perceptual states compared to the faster dynamics of adapting networks and the still faster dynamics of individual action potentials. Finally, the same consensus of neuronal activity across ascending and descending pathways linking multiple cortical areas that in anatomic sequence subserve phenomenal visual experiences and object recognition may underlie the normal unity of conscious experience.