: The concept of attention as central to human performance extends back to the start of experimental psychology, yet even a few years ago, it would not have been possible to outline in even a preliminary form a functional anatomy of the human attentional system. New developments in neuroscience have opened the study of higher cognition to physiological analysis, and have revealed a system of anatomical areas that appear to be basic to the selection of information for focal (conscious) processing. The importance of attention is its unique role in connecting the mental level of description of processes used in cognitive science with the anatomical level common in neuroscience. Sperry describes the central role that mental concepts play in understanding brain function. As is the case for sensory and motor systems of the brain, our knowledge of the anatomy of attention is incomplete. Nevertheless, we can now begin to identify some principles of organization that allow attention to function as a unified system for the control of mental processing. Although many of our points are still speculative and controversial, we believe they constitute a basis for more detailed studies of attention from a cognitive-neuroscience viewpoint. Perhaps even more important for furthering future studies, multiple methods of mental chronometry, brain lesions, electrophysiology, and several types of neuro-imaging have converged on common findings.

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The Attention System of the Human Brain

Over 60 years ago, Selye1 recognized the paradox that the physiologic systems activated by stress can not only protect and restore but also damage the body. What links these seemingly contradictory roles? How does stress influence the pathogenesis of disease, and what accounts for the variation in vulnerability to stress-related diseases among people with similar life experiences? How can stress-induced damage be quantified? These and many other questions still challenge investigators. This article reviews the long-term effect of the physiologic response to stress, which I refer to as allostatic load.2 Allostasis — the ability to achieve stability through change3 — . . .

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Protective and Damaging Effects of Stress Mediators

In this review, we have described the function of MR and GR in hippocampal neurons. The balance in actions mediated by the two corticosteroid receptor types in these neurons appears critical for neuronal excitability, stress responsiveness, and behavioral adaptation. Dysregulation of this MR/GR balance brings neurons in a vulnerable state with consequences for regulation of the stress response and enhanced vulnerability to disease in genetically predisposed individuals. The following specific inferences can be made on the basis of the currently available facts. 1. Corticosterone binds with high affinity to MRs predominantly localized in limbic brain (hippocampus) and with a 10-fold lower affinity to GRs that are widely distributed in brain. MRs are close to saturated with low basal concentrations of corticosterone, while high corticosterone concentrations during stress occupy both MRs and GRs. 2. The neuronal effects of corticosterone, mediated by MRs and GRs, are long-lasting, site-specific, and conditional. The action depends on cellular context, which is in part determined by other signals that can activate their own transcription factors interacting with MR and GR. These interactions provide an impressive diversity and complexity to corticosteroid modulation of gene expression. 3. Conditions of predominant MR activation, i.e., at the circadian trough at rest, are associated with the maintenance of excitability so that steady excitatory inputs to the hippocampal CA1 area result in considerable excitatory hippocampal output. By contrast, additional GR activation, e.g., after acute stress, generally depresses the CA1 hippocampal output. A similar effect is seen after adrenalectomy, indicating a U-shaped dose-response dependency of these cellular responses after the exposure to corticosterone. 4. Corticosterone through GR blocks the stress-induced HPA activation in hypothalamic CRH neurons and modulates the activity of the excitatory and inhibitory neural inputs to these neurons. Limbic (e.g., hippocampal) MRs mediate the effect of corticosterone on the maintenance of basal HPA activity and are of relevance for the sensitivity or threshold of the central stress response system. How this control occurs is not known, but it probably involves a steady excitatory hippocampal output, which regulates a GABA-ergic inhibitory tone on PVN neurons. Colocalized hippocampal GRs mediate a counteracting (i.e., disinhibitory) influence. Through GRs in ascending aminergic pathways, corticosterone potentiates the effect of stressors and arousal on HPA activation. The functional interaction between these corticosteroid-responsive inputs at the level of the PVN is probably the key to understanding HPA dysregulation associated with stress-related brain disorders. 5. Fine-tuning of HPA regulation occurs through MR- and GR-mediated effects on the processing of information in higher brain structures. Under healthy conditions, hippocampal MRs are involved in processes underlying integration of sensory information, interpretation of environmental information, and execution of appropriate behavioral reactions. Activation of hippocampal GRs facilitates storage of information and promotes elimination of inadequate behavioral responses. These behavioral effects mediated by MR and GR are linked, but how they influence endocrine regulation is not well understood. 6. Dexamethasone preferentially targets the pituitary in the blockade of stress-induced HPA activation. The brain penetration of this synthetic glucocorticoid is hampered by the mdr1a P-glycoprotein in the blood-brain barrier. Administration of moderate amounts of dexamethasone partially depletes the brain of corticosterone, and this has destabilizing consequences for excitability and information processing. 7. The set points of HPA regulation and MR/GR balance are genetically programmed, but can be reset by early life experiences involving mother-infant interaction. 8. (ABSTRACT TRUNCATED)

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Brain corticosteroid receptor balance in health and disease.

The hippocampus is a target of stress hormones, and it is an especially plastic and vulnerable region of the brain. It also responds to gonadal, thyroid, and adrenal hormones, which modulate changes in synapse formation and dendritic structure and regulate dentate gyrus volume during development and in adult life. Two forms of structural plasticity are affected by stress: Repeated stress causes atrophy of dendrites in the CA3 region, and both acute and chronic stress suppresses neurogenesis of dentate gyrus granule neurons. Besides glucocorticoids, excitatory amino acids and N-methyl-D-aspartate (NMDA) receptors are involved in these two forms of plasticity as well as in neuronal death that is caused in pyramidal neurons by seizures and by ischemia. The two forms of hippocampal structural plasticity are relevant to the human hippocampus, which undergoes a selective atrophy in a number of disorders, accompanied by deficits in declarative, episodic, spatial, and contextual memory performance. It is important, from a therapeutic standpoint, to distinguish between a permanent loss of cells and a reversible atrophy.

Stress and hippocampal plasticity.

Stress and cognitive function

A group of 19 healthy elderly subjects previously shown to differ in terms of their cortisol levels over a 4 year period were administered a neuropsychological test battery assessing memory, attention, and language. Correlational analyses performed on various corticosteroid measures showed that the slope of the change in cortisol levels over time predicted cognitive deficits in this elderly population. Aged subjects showing a significant increase in cortisol levels with years and with high current basal cortisol levels were impaired on tasks measuring explicit memory and selective attention when compared to aged subjects presenting either decreasing cortisol levels with years or increasing cortisol levels with moderate current basal cortisol levels. We further showed that subjects presenting a decrease in cortisol levels with years performed as well as young healthy subjects with regard to cognitive performance. Thus, impaired cognitive performance was associated with recent evidence of hypothalamic-pituitary-adrenal (HPA) dysregulation and elevated basal cortisol levels. These results are consistent with recent animal studies showing the existence of subpopulations of aged rats that differ in HPA activity and cognitive performance. Finally, the pattern of cognitive results related to the cortisol history of subjects is in agreement with a role played by the hippocampus in age-related HPA dysfunction and cognitive performance.

https://www.jneurosci.org/content/jneuro/14/5/2893.full.pdf

AndréRoch Lecours

Papers

Basal cortisol levels and cognitive deficits in human aging

Longitudinal study of basal cortisol levels in healthy elderly subjects: Evidence for subgroups

The "Pure Form" of the phonetic disintegration syndrome (pure anarthria); anatomo-clinical report of a historical case.

Illiteracy and brain damage—1. Aphasia testing in culturally contrasted populations (control subjects)

Schizophasia and jargonaphasia