THE NEUROPHYSIOLOGICAL BASIS OF ANXIETY: A HYPOTHESIS E. GELLHORN, M.D., Ph.D.* Wir sind nichts; was wir suchen ¡st alles.—Friedrich Hölderlin Work, togoodpurpose, is [man's] mostpreciousprivilege.—Wilder Penheld Panic oferror is the death ofprogress.—A. N. Whitehead A physiological theory of fear and of its more chronic form, anxiety, must take as its starting point Cannon's work [i] which shows that rage and fear asjudged by the behavior ofa cat confronted by a barking dog are accompanied by an increased adrenomedullary secretion. Although the areas in the hypothalamus and mesencephalon from which reactions culminating in fight and flight can be elicited are not identical, they overlap to a considerable extent [2]. Moreover, on stimulation with increasing intensities, the same site (in the amygdala) evokes behavioral effects which pass from attention to fear and, finally, to rage [3]. On the other hand, recent work showed that fear and rage reactions are elicitable from different parts ofthe amygdala [4]. That stimulation ofthe cortex ofthe temporal lobe and also of the gyrus cinguli [5] calls forth fear but no aggressive (anger) reactions supports the assumption that fundamentally different neurological structures are involved in these emotions. Similarly, it was shown that a fearlike "crouching" response (but no aggressive reaction) was evoked from the dorsomedial nucleus ofthe thalamus [6]. These data suggest that although transitional states between fear and aggression (anger, rage) exist, these emotions are physiologically as distinct as they are psychologically. The fact that in acute fear the striated muscles lose their tone, thereby contributing to collapse, whereas during the aggressive emotions the muscle tone is greatly increased provides a * Professor Emeritus of Neurophysiology. Present address: 2 Fellowship Circle, Santa Barbara, California 93105. This study was supported by grant MH 06552-04 from the National Institutes of Health. 488 E. Gellhorn · Neurophysiological Basis ofAnxiety Perspectives in Biology and Medicine · Summer 1963 clue for the differentiation of the underlying neurophysiological mechanisms . An attempt will be made to discuss the latter in acute fear and chronic anxiety as well as in certain experimentally induced mixed states by applying the principles and experiences resulting from the study of experimental neuroses [7, ?a\, the physiology of the ergotropic and trophotropic systems1 [7, ?a, 8] and the laws of autonomic (hypothalamic) imbalance [9-11]· I. The Physiology ofAcute Fear In acute fear, blood pressure and heart rate may drop suddenly (for instance, at the sight of blood or due to severe pain), the tone of the striated muscles decreases, and the person faints (vasodepressor syncope), particularly if he was in an upright position. The loss of sympathetic vasomotor tone and/or the increase in vagal activity lead to a shift in the ergotropic-trophotropic balance to the trophotropic side. This change is aided by the loss in muscle tone since the latter counteracts circulatory collapse not only through its action on the venous return to the heart but also through the stimulating action of proprioceptive impulses on the ergotropic centers in the brain stem [12]. The study ofcirculation in states ofacute fear supports this interpretation: the minute volume ofthe heart and the blood pressure tend to fall [13] and vagal activity is greatly increased [14]. Nausea has likewise been shown to occur under these conditions [15]. The psychological attitude is one ofpassivity; the feeling ofbeing overwhelmed prevails when no possibility for an escape seems to exist. Fear in this setting may lead to vomiting, loss in muscle tone, and collapse [16]. It should be recalled that retching and vomiting can be elicited from the anterior hypothalamus and are the expression oftrophotropic discharges. Whether acute fear is accompanied by nausea or not, it is certain that when the subjective emotion reaches an adequate intensity, the classical triad constituting the trophotropic syndrome prevails: the potentials in the EEG are slowed [12], parasympathetic discharges are increased, and the tone ofthe skeletal muscles is inhibited via the gamma system. 1 In view ofthe common association ofsympathetic discharges with motor activity and cortical excitation—and of parasympathetic discharges with inhibition of movements, synchronization of cortical potentials, and rest—the former syndrome reflects, in Hcss's terms, the state ofthe ergotropic system and the latter that ofthe trophotropic system...