FOREBRAIN REGIONS ASSOCIATED WITH HYPOTHALAMUS The cerebral cortex influences the “autonomic” neurovisceral outflow and the neurohumoral output of the endocrine glands, as can be demonstrated experimentally by stimulating the orbitofrontal cortex of the cingulate gyrus to produce respiratory, cardiovascular, and digestive responses, as well as certain emotional reactions. The responses are less marked than those produced by stimulating the hypothalamus but are still striking; some of them, moreover, do not depend upon the integrity of the hypothalamus, a fact that suggests mediation by corticoreticular fibers to lower “centers.” In humans, subjective emotional experiences are associated with autonomic discharges (e.g., tachycardia, increased blood pressure, blushing) and changes in endocrine activity (e.g., stress-induced amenorrhea or anorexia nervosa). Behavioral changes produced by cortical ablations, such as prefrontal lobotomy, are well known. Other such changes, varying from mania and hyperphagia to apathy, aphagia, and somnolence, result from lesions to certain parts of the hypothalamus. Plate 2-12 Thus hypothalamic circuitry is tied into countless other circuits in the cerebral cortex, limbic system, brainstem reticular formation, and other parts of the diencephalon. These circuits are poorly understood, but rich connections with the frontotemporal and cingulate cortex, septal/preoptic areas, amygdala, anterior mesencephalic tegmentum, and numerous thalamic nuclei (midline, intralaminar, medial posterior, anterior, etc.) have been demonstrated. Some of these connections are indicated schematically in the illustration. Connections between the orbital cortex of the frontal lobe and the hypothalamus have been demonstrated in certain mammals. Indirect connections with the prefrontal areas through the medial posterior thalamic nucleus are well established. The hypothalamus is linked with the cingulate gyrus by way of the anterior thalamic nuclei and with the hippocampal formation via the fornix. The amygdala has reciprocal connections with the hypothalamus through the anterior amygdalofugal pathway. Additional amygdalohypothalamic connections run through the stria terminalis. The hypothalamus also receives input, through reticulohypothalamic fiber systems departing from the main reticulothalamic stream, from the great sensory systems. Through this offshoot, the responses evolved through thalamocortical feature analysis are paralleled by responses in the visceral realm. The limbic (border) structures of the cerebral hemisphere also participate in these responses: the olfactory bulb, amygdala, frontotemporal cortex, septal nuclei, hippocampal formation, and limbic lobe. Stimulation of limbic structures can produce respiratory and vascular changes, and psychotropic drugs, such as mescaline, apparently exert some of their effects on the limbic system. The stria medullaris thalami and medial forebrain bundle deserve mention: the former bypasses the hypothalamus, the latter runs right through it. The stria medullaris thalami connects the medial olfactory area, amygdala and preoptic area with the habenular nucleus, from which fibers pass to the interpeduncular region. The medial forebrain bundle links the anteromedial olfactory areas with the preoptic areas, hypothalamus, and mesencephalic tegmentum. A diffuse system of fine fibers, it pervades the lateral hypothalamic area and is the key fiber tract of the hypothalamus. Lastly, fibers of the fornix end in both medial and lateral mammillary nuclei, as well as in the hypothalamus anterior to the mammillary region. A few fibers pass caudally into the mesencephalon.