Dorsolateral prefrontal cortex

Aoki, C.,Venkatesan, C., Go, C. G., Forman, R. and Kurose, H. Cellular and subcellular sites for noradrenergic action in the monkey dorsolateral prefrontal cortex as revealed by the immunocytochemical localization of noradrenergic receptors and axons. Cereb. Cortex 8 269-277,1998. 

Weinberger, D. R., Berman, K. F. and Zee, R. F. Physiologic dysfunction of dorsolateral prefrontal cortex in schizophrenia. I. Regional cerebral blood flow evidence. Arch. Gen. Psychiatry 43 114-124,1986. 

Functional imaging studies (Ch. 58) in human addicts have found that cue-elicited craving is associated with activation of the amygdala, the anterior cingulate cortex, the orbitofrontal cortex, and the dorsolateral prefrontal cortex [18]. Activation of other regions has been reported less consistently. The amygdala is critical for associative... 

Xu et al. (2005) 8 NA 4.1 14.4 N-Back Task-related neural activity in the left DLPFC showed a significant interaction between test session working memory load. When smokers had smoked ad libitum, task-related activity in the left dorsolateral prefrontal cortex was relatively low for an easy task condition (1-back), and increased as task difficulty increased but when smokers were abstinent overnight, activity in the L-DLPFC was approximately as high at low task level as it was at more difficult levels. 

In studies examining regional activity responses to nicotine or smoking, the most common findings are relative increases in activity in the prefrontal cortex (including the dorsolateral prefrontal cortex, and inferior frontal, medial frontal, and... 

Repetitive TMS, unlike electroconvulsive therapy (ECT), uses sub-convulsive stimuli to treat depression. Compared to ECT, TMS has a potential to target specific brain regions and to stimulate brain areas thought to be primarily involved in depression while sparing areas like the hippocampus, thereby reducing the probability of cognitive side effects. However, the therapeutic efficacy of TMS as a treatment for depression is, unlike ECT, modest. Most TMS studies use high-frequency, fast stimulation (> 10 Hz) over the left dorsolateral prefrontal cortex, an area which has been... 

Li B-M, Mei ZT (1994) Delayed response deficit induced by local injection of the alpha-2 adrenergic antagonist yohimbine into the dorsolateral prefrontal cortex in young adult monkeys. Behav Neural Biol 62 134-139... 

There is an emerging literature in MRS in adults with BD, with reports of decreases in dorsolateral prefrontal cortex of neuronal marker NAA (Winsberg et al., 2000) and abnormalities in phopholipid metabolism (Kato et ah, 1995, 1998 Hamakawa et ah, 1999). There is preliminary work to suggest that cortical GABA levels and glutamate turnover are decreased in unipolar depression in adults, but these abnormalities may not be present in bipolar depression (Sanacora et al., 1999, Mason et al., 2000). 

Pascual-Leone, A., Rubio, B., Pallardo, R, and Catala, M.D. (1996) Rapid-rate trancranial magnetic stimulation of left dorsolateral prefrontal cortex in drug-resistant major depression. Lancet 34S 233-237. 

Avery, R., Franowicz, J.C.S., Studholme C., van Dyck C.H., and Arnsten, A.F.T. (2000) The alpha-2A adrenoceptor agonist, guanfacine, increases regional cerebral blood flow in dorsolateral prefrontal cortex and improves accuracy in monkeys performing a spatial working memory task. Neuropsychopharmacology 23 240-249. 

Now we need to tie the priming with its residual activation of dorsolateral prefrontal cortex neuronal networks to the emergence, in REM, of a reactivation of those networks. I propose that the residual activation of the dorsolateral prefrontal cortex is amplified by the REM activation of these other cortical networks that produce dream bizarreness via the associative resonance that the dorsolateral prefrontal cortex has been primed to detect. And indeed, the dawning awareness that this must be a dream feels, subjectively, like a positive feedback process. Once the recognition has been inserted into delusional process it is enhanced by the mounting evidence of delusion that it observes ... 

These decreases in the I function occur in trance because external stimulus strength declines. We now note that the opposite movement of the I function in lucidity is the reciprocal enhancement of inputs external to the REM system, but rather than coming from the outside world, they come from the primed dorsolateral prefrontal cortex, which has been instructed to notice—and act on—dream bizarreness by dissociating itself from REM. 

In this hierarchical scheme, the dorsolateral prefrontal cortex is a head ganglion for deliberate decision making, an arbiter and executor of conscious processing, and a director of what we call our will. No doubt oversimplified and minimizing for heuristic purposes what must be constant and massively parallel interactions with other parts of the system, this model is particularly attractive in the context of our conscious state paradigm. 

The dorsolateral prefrontal area is a cortical region that shows consistent and conspicuous deactivation during REM sleep compared to waking. Other areas (vide infra) are more active, but the dorsolateral prefrontal cortex is less active. What might this observation mean at the level of mechanism and function ... 

I will address the mechanistic implications in the following section on cortico-limbic interaction. With respect to function, the most immediate and compelling hypothesis is that the subtraction of the dorsolateral prefrontal cortex from the otherwise highly activated forebrain maps on to the subtraction from waking consciousness of self-reflective awareness (self-evaluation), lack of capacity to direct thought (active evaluation), and failure to enact deliberate behaviors, however fictive, in dreaming consciousness (volition). 

Add to this mix the conspicuous failure of recent memory to keep dream data in mind for more than a very few minutes and we can consider one of the great dream mysteries (amnesia) to be tentatively solved it is the joint product of the global aminergic demodulation that affects the entire brain and the more local disenablement of the dedicated circuitry of the dorsolateral prefrontal cortex that, in waking, allows us to be critical, decisive, and executive. 

The net effect is to push the brain in a very REM dream-like direction. PET studies of schizophrenic patients brains show deficient frontal cortical activation and limbic overactivation. The working hypothesis of schizophrenia investigators is that psychosis results when the overactive mesolimbic pathway is released from deficient cortical control. This is formally identical to our hypothesis of dream psychosis the dorsolateral prefrontal cortex is deactivated and the limbic system is hyperactivated. 

But whatever the neuromodulatory status of mania, it makes sense to reason that the exuberant positive emotion, emanating from a hyperactive limbic system, is unchecked by a relatively impoverished dorsolateral prefrontal cortex. Hence, the poor judgment and the disastrous social indiscretions are the result of takeover of the brain by parasitic internal stimuli just as occurs in epilepsy and in dream psychosis ... 

All of this is, of course, standard practice in cognitive behavioral therapy, and I do not pretend that it is in itself innovative. My only contribution is to show how comfortably it sits on the solid foundation of the mind-brain paradigm. At the same time, it calls forth from that paradigm a mechanistic model of change at the level of the brain, namely a shift in balance and in specific connections between the executive functions of the dorsolateral prefrontal cortex and the limbic system. 

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