Chapters 11 & 12

Anatomy of the limbic forebrain

Now that we have nearly completed our brief survey of human brain anatomy, let's make one final pass through the forebrain, focusing on structures that have been considered parts of the "limbic system". A subset of these are crucial for understanding the brain basis of human cognition and biological psychiatry, so this survey would not be complete without another look at the human brain with these components in view.

Attempts to understand the control of emotional behavior have a long history. In 1937, James Papez first proposed that specific brain circuits are devoted to emotional experience and expression. In seeking to understand what parts of the brain serve this function, he began to explore the medial aspects of the cerebral hemisphere. In 1878, Paul Broca used the term "limbic lobe" (le grand lobe limbique) to refer to the part of the cerebral cortex that forms a rim ("limbus" is Latin for rim) around the corpus callosum and diencephalon on the medial face of the hemispheres. Two prominent components of this region are the cingulate gyrus, which lies above the corpus callosum, and the parahippocampal gyrus, which lies in the medial temporal lobe. For many years, these two structures, along with the olfactory bulbs, were thought to be concerned primarily with the sense of smell. Indeed, Broca considered the olfactory bulbs to be
the principal source of input to the limbic lobe. Papez, however, speculated that the function of the limbic lobe might be more related to emotions. He knew that the hypothalamus influences the expression of emotion; he also of course knew that emotions reach consciousness and that higher cognitive functions affect emotional behavior. Ultimately, Papez showed that the cingulate cortex and hypothalamus are interconnected via projections from the mammillary bodies (part of the posterior hypothalamus) to the anterior nucleus of the thalamus, which projects in turn to the cingulate gyrus; the cingulate gyrus (like many other
cortical regions) projects to the hippocampus. Finally, he showed that the hippocampus (actually, the subiculum, a division of the hippocampal formation) projects via the fornix (a large fiber bundle) back to the hypothalamus and septal region. Papez suggested that these pathways, which became known as the "Papez circuit," provide the connections necessary for cortical control of emotional expression.

Over time, the concept of a forebrain circuit for the control of emotional expression has been revised to include parts of the orbital and medial prefrontal cortex, ventral parts portions of the basal ganglia—most importantly, the nucleus accumbens, the mediodorsal nucleus of the thalamus (a different thalamic nucleus than the one Papez emphasized), and the amygdala, a large nuclear mass in the temporal lobe anterior to the hippocampus. This set of structures, together with the parahippocampal gyrus and cingulate cortex, is generally referred to as the limbic system (Figure A4-1). Thus, some of the structures that Papez originally described (the hippocampus, for example) now appear to have little primary role in emotional processing, whereas the amygdala, which Papez hardly mentioned, clearly plays a major role in the experience and expression of emotion.

In order to know which groups of structures in the limbic forebrain are associated mainly with particular aspects of sensation and cognition, it is helpful to recognize three basic groupings or divisions:

• an olfactory division, concerned with the encoding of olfactory signals and engaging behaviors motivated by air-borne stimuli;
• a parahippocampal division, centered in the medial temporal lobe, that is mainly concerned with explicit representation and the acquisition and retrieval of declarative (episodic) memory;
• an amygdaloid/orbital prefrontal division encompasses a network of telencephalic and diencephalic structures with the amygdala and related sectors of the orbital and medial prefrontal cortex as key nodes; this division is primarily concerned with implicit representation, which becomes manifest in the experience and expression of emotion and emotional behavior.

Thus, it is the amygdaloid/orbital prefrontal division that is most germane for understanding the brain basis of emotion and motivated behavior. Through an illuminating history of empirical findings and clinical observations in both experimental animals and humans, it is now clear that the amygdala mediates neural processes that invest sensory experience with emotional significance in a form of associative learning, particularly when the sensory experience signals threat. Indeed, it is not too much of a stretch to characterize the amygdala (and its telencephalic and diencephalic connections) as an "early warning system" being especially well-tuned to social cues and environmental stimuli that signal threat. Neuroanatomically, the amygdala is a complex mass of gray matter buried in the anterior-medial portion of the temporal lobe, just rostral to the hippocampus (Figure A4-2). It comprises multiple, distinct subnuclei and cortical regions that are richly connected to nearby cortical areas on the ventral and medial aspect of the hemispheric surface.

The amygdala (or amygdaloid complex) can understood in terms of three major functional and anatomical subdivisions, each of which has a unique set of connections with other parts of the brain. The medial group of subnuclei has extensive connections with the olfactory bulb and the olfactory cortex. The basal-lateral group, which is especially large in humans, has major connections with the cerebral cortex, especially the orbital and medial prefrontal cortex and the
associational cortex of the anterior temporal lobe (Figure A4-3). These cortical fields associate information from every sensory modality (including information about visceral activities) and can thus integrate a variety of inputs pertinent to moment-to-moment experiences. In addition, the basal-lateral group projects to the thalamus (specifically, to the mediodorsal nucleus), which projects in turn to these same cortical areas. This same group also innervates neurons in the nucleus accumbens that receive the major cortico-striatal projections from the prefrontal cortex and parahippocampal gyrus. Lastly, the central group of nuclei is characterized by connections with the hypothalamus and brainstem, linking the amygdala with autonomic, neuroendocrine and somatic effector systems.

Considering all these seemingly arcane anatomical connections, the amygdala emerges as a key node in a network that links together the cortical and subcortical brain regions involved in emotional processing and the expression of emotional behavior. More generally, the amygdala and its connections to the prefrontal cortex and basal ganglia are likely to influence the selection and initiation of behaviors aimed at obtaining rewards and avoiding punishments (recall
that the process of program selection and initiation is an important function of basal ganglia circuitry). The parts of the prefrontal cortex interconnected with the amygdala are also involved in organizing and planning future behaviors. Thus, the amygdala may provide emotional input to overt (and covert) deliberations of that bias decision-making.

Finally, it is likely that interactions between the amygdala, the neocortex and related subcortical circuits account for what is perhaps the most enigmatic aspect of emotional experience: the highly subjective "feelings" that attend most emotional states. Although the neurobiology of such experience is not understood, it is reasonable to assume that emotional feelings arise as a consequence of a more general cognitive capacity for self-awareness. In this conception, feelings entail both the immediate conscious experience of implicit emotional processing (arising from amygdala–neocortical circuitry) and the explicit processing of semantically based thought (arising from hippocampal–neocortical circuitry). It is plausible to conceptualize feelings as the product of an 'emotional working memory' that sustains neural activity related to the processing of these various elements of emotional experience. Given the evidence for working memory functions in the prefrontal cortex, this portion of the frontal lobe—especially the orbital and medial sector—is the likely neural substrate where such associations are maintained in conscious awareness.