BOSTON—Once considered too intangible to study, the mysteries of emotion and consciousness are now beginning to be unraveled with neuroimaging techniques and molecular biology. "Rather than being elusive, emotion is as much amenable to scientific study as any other aspect of the mind," said Antonio R. Damasio, MD, PhD, Professor and Head of the Department of Neurology at the University of Iowa College of Medicine, Iowa City, and Adjunct Professor at the Salk Institute, in La Jolla, California. During the 125th Annual Meeting of the American Neurological Association, Dr. Damasio and other researchers in the field of cognitive neuroscience discussed the roles of emotion, memory, and consciousness in the definition and management of various neurologic and psychiatric disorders.

THE SEARCH FOR THE EMOTION LOCUS

According to Dr. Damasio, emotion is an "expression of basic mechanisms of life regulation developed in evolution and is indispensable for survival." The neural systems related to emotion appear to be selective, he noted. Patients with bilateral amygdala damage have been shown to have difficulty processing fear and anger, and they cannot recognize these emotions in others. These patients, he added, have no difficulty with other emotions.

With the advent of positron emission tomography (PET), researchers began looking for the physical substrates of emotion and feeling. When subjects were asked to imagine and reenact emotional states, there were "profound changes" in the PET images, Dr. Damasio said. Feeling the emotion of sadness, for instance, resulted in bilateral insular cortex activation and partial activation of the cingulate gyrus. Feeling happiness activated the insula cortex in a slightly different pattern and also activated the posterior cingulate and secondary somatosensory cortex. Feeling fear resulted in deactivation of secondary somatosensory regions, he said.

DISORDERS OF CONSCIOUSNESSŠ

"Consciousness is in the direct line of succession from emotions and feeling," Dr. Damasio proposed. He referred to consciousness as a combination of two processes. One process can be thought of as the "movie in the brain" that spatially and temporally integrates the pattern of mental images of varied sensory types. The other process is the "self" that senses that the movie happens to be yours. The movie is shot in "your perspective" and "you can act on its contents as agents." In this context, he said that patients with akinetic autism, absence seizures, global amnesia, and coma provide prime examples of disorders of consciousness.

The distinction between "self" and "others" can be considered a specific neuronal task that, when altered, can lead to pathologic states, said John C. Mazziotta, MD, PhD, Professor of Neurology, Radiological Sciences, and Molecular and Medical Pharmacology and Director of the Brain Mapping Center at the University of California, Los Angeles.

"We constantly monitor and imitate the actions of others," Dr. Mazziotta said. Indeed, mirror neurons respond when a subject performs a complex motor task or watches another individual performing the same task. Shared motor representations may allow us to develop empathy and to learn languages, accents, and social gestures, he said. When a subject looks at a person who has an expression of sadness, for example, the subject preactivates his or her own muscles that express sadness.

However, the discovery of mirror neurons has led to further questions about how we retain a sense of self. Proprioception, Dr. Mazziotta observed, seems to be a crucial component in this distinction. Studies of patients with dorsolateral prefrontal lesions, he continued, suggest that this region may be required to suppress the automatic mimicking of others. Therefore, "pathologic aberrations of this inhibition may result in symptoms associated with echolalia, echopraxia, autism, and schizophrenia," he said.

SUBCONSCIOUS COMPUTATIONS

Although the brain performs a vast number of neuronal computations, few result in conscious awareness, Dr. Mazziotta said. A recent imaging study suggested that visual awareness is the result of subconscious computations. According to the study, viewing an ambiguous figure results in competing percepts within the brain. Using functional magnetic resonance imaging, the researchers captured a salient state in which higher-order visual areas were activated while the primary visual cortex was deactivated. Although Dr. Mazziotta acknowledged that current imaging techniques have limited spatial and temporal resolutions, they can be used to begin exploring the nature of consciousness.

DECISION-MAKING DEVICE

"The highly structured nervous system serves as an exquisite decision-making device," said Michael S. Gazzaniga, PhD, Director of the Center for Cognitive Neuroscience at Dartmouth College, Hanover, New Hampshire. "From perception to rational choice, the brain functions automatically even as we struggle to believe we freely will our own actions," he said.

Studies of split-brain patients have yielded insights into the organization of the sensory and motor systems and, perhaps, clues to the nature of conscious experience. Although the left hemisphere is specialized for language, speech, and major problem-solving capacities and the right hemisphere is specialized for tasks such as facial recognition and attentional monitoring, processes that require activities in both hemispheres seem totally integrated, Dr. Gazzaniga said. Even when the corpus callosum is severed, and the two hemispheres act independently, "we believe that we are in charge of our actions," he said. The rules of human nature, he suggested, are "enacted before personal conscious awareness." According to Dr. Gazzaniga, "these phenomena appear to be related to our left hemisphere's interpreter, a device that allows us to construct theories about the relationship between perceived events, actions, and feelings."

MEMORY, LEARNING, & GENETICS

"Consciousness is meaningless without memory," said Tim Tully, PhD, a Professor from the Cold Spring Harbor Laboratory, in New York. Therefore, he speculated, memory enhancement may be a potentially effective treatment for various forms of cognitive dysfunction.

From a neurogenetic perspective, learning and memory impairment may be caused by defects in the genome. In order to identify the comprehensive network of genes involved in memory formation, Dr. Tully studied fruit flies. The Drosophilagenome, he explained, has been completely mapped and the identification of memory genes in flies could lead to the identification of human homologs.

Using olfactory conditioning as a model for memory and learning, Dr. Tully and colleagues demonstrated that flies could develop a "photographic memory" simply by upregulating the cyclic AMP-response element binding (CREB) protein. Cyclic AMP metabolism is thought to have a critical role in the consolidation of short-term changes in neuronal activity into long-term memory storage in a variety of systems ranging from the gill and siphon withdrawal reflex in Aplysiato spatial and contextual learning in mice. Although extrapolation to humans may not be straightforward, Dr. Tully suspects that human memory could eventually be reduced to the expression of genes that fine-tune the neural circuitry underlying consciousness.

NR