Medial and orbital frontal cortex in decision-making and flexible behavior

Klein-Flügge, M. C., Bongioanni, A., & 

Rushworth, M. F. (2022).

Neuron.

https://doi.org/10.1016/j.neuron.2022.05.022

Summary

The medial frontal cortex and adjacent orbitofrontal cortex have been the focus of investigations of decision-making, behavioral flexibility, and social behavior. We review studies conducted in humans, macaques, and rodents and argue that several regions with different functional roles can be identified in the dorsal anterior cingulate cortex, perigenual anterior cingulate cortex, anterior medial frontal cortex, ventromedial prefrontal cortex, and medial and lateral parts of the orbitofrontal cortex. There is increasing evidence that the manner in which these areas represent the value of the environment and specific choices is different from subcortical brain regions and more complex than previously thought. Although activity in some regions reflects distributions of reward and opportunities across the environment, in other cases, activity reflects the structural relationships between features of the environment that animals can use to infer what decision to take even if they have not encountered identical opportunities in the past.

Summary

Neural systems that represent the value of the environment exist in many vertebrates. An extended subcortical circuit spanning the striatum, midbrain, and brainstem nuclei of mammals corresponds to these ancient systems. In addition, however, mammals possess several frontal cortical regions concerned with guidance of decision-making and adaptive, flexible behavior. Although these frontal systems interact extensively with these subcortical circuits, they make specific contributions to behavior and also influence behavior via other cortical routes. Some areas such as the ACC, which is present in a broad range of mammals, represent the distribution of opportunities in an environment over space and time, whereas other brain regions such as amFC and dmPFC have roles in representing structural associations and causal links between environmental features, including aspects of the social environment (Figure 8). Although the origins of these areas and their functions are traceable to rodents, they are especially prominent in primates. They make it possible not just to select choices on the basis of past experience of identical situations, but to make inferences to guide decisions in new scenarios.

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Proposal for Revising the Uniform Determination of Death Act

Hastings Bioethics Center

Originally posted 18 FEB 22

Organ transplantation has saved many lives in the past half-century, and the majority of postmortem organ donations have occurred after a declaration of death by neurological criteria, or brain death. However, inconsistencies between the biological concept of death and the diagnostic protocols used to determine brain death–as well as questions about the underlying assumptions of brain death–have led to a justified reassessment of the legal standard of death. We believe that the concept of brain death, though flawed in its present application, can be preserved and promoted as a pathway to organ donation, but only after particular changes are made in the medical criteria for its diagnosis. These changes should precede changes in the Uniform Determination of Death Act (UDDA).

The UDDA, approved in 1981, provides a legal definition of death, which has been adopted in some form by all 50 states. It says that death can be defined as the irreversible cessation of circulatory and respiratory functions or of brain functions. The act defines brain death as “irreversible cessation of all functions of the entire brain, including the brainstem.” This description is based on a widely held assumption at the time that the brain is the master integrator of the body, such that when it ceases to function, the body would no longer be able to maintain integrated functions. It was presumed that this would result in both cardiac and pulmonary arrest and the death of the body as a whole. Now that assumption has been called into question by exceptional cases of individuals on ventilators who were declared brain dead but who continued to have function in the hypothalamus. 

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Revision of the UDDA should first defer to a revision of the guidelines. Clinical criteria for the diagnosis of “cessation of all functions of the entire brain” must include all pertinent functions, including hypothalamic functions such as hormone release and regulation of temperature and blood pressure, to avoid the specter of neurologic recovery in those who fulfill the current clinical criteria for the diagnosis of brain death.

It is likely that the failure to account for a full set of pertinent brain functions has led to inconsistent diagnoses and conflicting results. Such inconsistencies, although well-documented in a number of cases, may have been even more frequent but unrecognized because declaration of brain death is often a self-fulfilling prophecy: rarely do any life-sustaining interventions continue after the diagnosis is made.

To be consistent, transparent, and accurate, the cessation of function in both the cardiopulmonary and the neurological standard of the UDDA should be described as permanent (i.e., no reversal will be attempted) rather than irreversible (i.e., no reversal is possible). We recognize additional challenges in complying with the UDDA requirements that these cessation criteria for brain death include “all functions” of the “entire brain.” In the absence of universally accepted and easily implemented testing criteria, there may be real problems with being in perfect compliance with these legal criteria in spite of being in perfect compliance with the currently published medical guidelines. If the concept of brain death is philosophically valid, as we think is defensible, then the diagnostic guidelines should be corrected before any attempt is made to correct the UDDA. They must then “say what they mean and mean what they say” to eliminate any possibility of patients with persistent evidence of brain function, including hypothalamic function, being erroneously declared brain dead.

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