Unexpected global impact of VTA dopamine neuron activation as measured by opto-fMRI.

Dopamine neurons in the ventral tegmental area (VTA) are strongly implicated in cognitive and affective processing as well as in psychiatric disorders, including schizophrenia, depression, attention-deficit hyperactivity disorder and substance abuse disorders. In human studies, dopamine-related functions are routinely assessed using functional magnetic resonance imaging (fMRI) measures of blood oxygenation-level-dependent (BOLD) signals during the performance of dopamine-dependent tasks. There is, however, a critical void in our knowledge about whether and how activation of VTA dopamine neurons specifically influences regional or global fMRI signals. Here, we used optogenetics in Th::Cre rats to selectively stimulate VTA dopamine neurons while simultaneously measuring global hemodynamic changes using BOLD and cerebral blood volume-weighted (CBVw) fMRI. Phasic activation of VTA dopamine neurons increased BOLD and CBVw fMRI signals in VTA-innervated limbic regions, including the ventral striatum (nucleus accumbens). Surprisingly, basal ganglia regions that receive sparse or no VTA dopaminergic innervation, including the dorsal striatum and the globus pallidus, were also activated. In fact, the most prominent fMRI signal increase in the forebrain was observed in the dorsal striatum that is not traditionally associated with VTA dopamine neurotransmission. These data establish causation between phasic activation of VTA dopamine neurons and global fMRI signals. They further suggest that mesolimbic and non-limbic basal ganglia dopamine circuits are functionally connected and thus provide a potential novel framework for understanding dopamine-dependent functions and interpreting data obtained from human fMRI studies.

Submillimeter-resolution fMRI: Toward understanding local neural processing.

Functional magnetic resonance imaging (fMRI) measures the hemodynamic response to active neurons. The most prevailing fMRI contrast, blood oxygenation level-dependent (BOLD) contrast, specifically results from a complex interplay between oxygen metabolism, blood flow, and blood volume reactions. Therefore, because fMRI indirectly measures brain function, the spatial accuracy of these blood-borne signal changes to the true neuronal activity comes into question, especially at high resolutions. To better interpret the neural basis of fMRI, these properties have been studied in localized neural circuits of the brain using fMRI with blood flow, blood volume, and BOLD contrasts, as well as optical intrinsic signal imaging (OISI), which shares similar signal sources as fMRI. Here, we review how submillimeter-scale high-resolution fMRI and OISI in the visual cortex columnar and olfactory bulb laminar models have advanced our basic knowledge of the spatial localization of the individual hemodynamic signals and neurovascular coupling mechanisms.

The function of one-word mediators in the recall of word pairs.

The problem of demonstrating that natural language mediators play a role in learning and are not epiphenomena resulting from learning is an important problem in cognitive learning theories. Using a cued-recall and a free-recall learning task, Ss were requested to add a one-word mediator to some of the pairs of concrete nouns presented, The mediated pairs were learned better than the control pairs in both tasks. Both words were recalled only when the mediator was also recalled. Also, one-word mediators were the most effective recall cues and were the best recalled words in free recall. A two-stage learning model adequately described the data. However, a counterargument can be made which considers the mediator to be a high associate of one of the words presented and actually has no direct link to the other presented word. A possible experimental resolution of the problem is discussed.