A functional MRI study of mental image generation http://www.sciencedirect.com/science/article/pii/S0028393296001212 The neural substrates of mental image generation were investigated with functional MRI. Subjects listened to words under two different instructional conditions: to generate visual mental images of the words' referents, or to simply listen to each word and wait for the next word. Analyses were performed which directly compared the regional brain activity during each condition, with the goal of discovering whether mental image generation engages modality-specific visual areas, whether it engages primary visual cortex, and whether it recruits the left hemisphere to a greater extent than the right. Results revealed that visual association cortex, and not primary visual cortex, was engaged during the mental image generation condition. Left inferior temporal lobe (Brodmann's area 37) was the most reliably and robustly activated area across subjects, but some subjects had activity which extended superiorly into occipital association cortex (area 19). The results of this experiment support the hypothesis that visual mental imagery is a function of visual association cortex, and that image generation is asymmetrically localized to the left. visual association cortex primary visual cortex ----------------------------- Effects of bromocriptine on human subjects depend on working memory capacity http://journals.lww.com/neuroreport/Abstract/1997/11100/Effects_of_bromocriptine_on_human_subjects_depend.32.aspx PHARMACOLOGICAL manipulation of brain dopamine concentration affects visuospatial working memory in humans and in animals, the latter effects localized to the prefrontal cortex. However, the effects of dopamine agonists on humans are poorly understood. We hypothesized that bromocriptine would have an effect on cognitive functions associated with the prefrontal cortex via its effects on cortical dopamine receptors and on subcortical receptors in areas that project to the neocortex. We found that the effect of bromocriptine on young normal subjects depended on the subjects' working memory capacity. High-capacity subjects performed more poorly on the drug, while low-capacity subjects improved. These results demonstrate an empirical link between a dopamine-mediated working memory system and higher cognitive function in humans. bromocriptine ------------------------- Methylphenidate enhances working memory by modulating discrete frontal and parietal lobe regions in the human brain -------------------- Inverted-U dopamine D1 receptor actions on prefrontal neurons engaged in working memory http://www.nature.com/neuro/journal/v10/n3/abs/nn1846.html Dopamine (DA) D1 receptor (D1R) stimulation in prefrontal cortex (PFC) produces an 'inverted-U' dose-response, whereby either too little or too much D1R stimulation impairs spatial working memory. This response has been observed across species, including genetic linkages with human cognitive abilities, PFC activation states and DA synthesis. The cellular basis for the inverted U has long been sought, with in vitro intracellular recordings supporting a variety of potential mechanisms. The current study demonstrates that the D1R agonist inverted-U response can be observed in PFC neurons of behaving monkeys: low levels of D1R stimulation enhance spatial tuning by suppressing responses to nonpreferred directions, whereas high levels reduce delay-related firing for all directions, eroding tuning. These sculpting actions of D1R stimulation are mediated in monkeys and rats by cyclic AMP intracellular signaling. The evidence for an inverted U at the cellular level in behaving animals promises to bridge in vitro molecular analyses with human cognitive experience. ----------------------------------------------------------------------------------- Individual capacity differences predict working memory performance and prefrontal activity following dopamine receptor stimulation http://link.springer.com/article/10.3758/CABN.5.2.212 Dopamine receptors are abundant in the prefrontal cortex (PFC), a critical region involved in working memory. This pharmacological fMRI study tested the relationships between dopamine, PFC function, and individual differences in working memory capacity. Subjects performed a verbal delayed-recognition task after taking either the dopamine receptor agonist bromocriptine or a placebo. Behavioral effects of bromocriptine treatment depended on subjects’ working memory spans, with the greatest behavioral benefit for lower span subjects. After bromocriptine, PFC activity was positively correlated with a measure of cognitive efficiency (RT slope) during the probe period of the task. Less efficient subjects with slower memory retrieval rates had greater PFC activity, whereas more efficient subjects had less activity. After placebo, these measures were uncorrelated. These results support the role of dopamine in verbal working memory and suggest that dopamine may modulate the efficiency of retrieval of items from the contents of working memory. Individual differences in PFC dopamine receptor concentration may thus underlie the behavioral effects of dopamine stimulation on working memory function. ----------------------------------------------------------------------------------- Individuals lower in working memory capacity are particularly vulnerable to anxiety's disruptive effect on performance radial unit hypothesis surface area (not cortical thickness) Trnp1