Neuroanatomical correlates of anticipatory anxiety.

Positron emission tomographic measurements of regional blood flow, a marker of local neuronal activity, were used to investigate the neuroanatomical correlates of a normal emotion. Healthy volunteers were studied before, during, and after anticipation of a painful electric shock. During anticipatory anxiety, there were significant blood flow increases in bilateral temporal poles, the same regions recently implicated in a lactate-induced anxiety attack in patients with panic disorder. Thus, the temporal poles seem to be involved in normal and pathological forms of human anxiety.

Reproducibility of cerebral glucose metabolic measurements in resting human subjects.

Positron emission tomography with 11C-2-deoxyglucose was used to determine the test-retest variability of regional cerebral glucose metabolism in 22 young normal right-handed men scanned twice in a 24-h period under baseline (resting) conditions. To assess the effects of scan order and time of day on variability, 12 subjects were scanned in the morning and afternoon of the same day (a.m.-p.m.) and 10 in the reverse order (p.m.-a.m.) with a night in between. The effect of anxiety on metabolism was also assessed. Seventy-three percent of the total subject group showed changes in whole brain metabolism from the first to the second measurement of 10% or less, with comparable changes in various cortical and subcortical regions. When a scaling factor was used to equate the whole brain metabolism in the two scans for each individual, the resulting average regional changes for each group were no more than 1%. This suggests that the proportion of the whole brain metabolism utilized regionally is stable in a group of subjects over time. Both groups of subjects had lower morning than afternoon metabolism, but the differences were slight in the p.m.-a.m. group. One measure of anxiety (pulse at run 1) was correlated with run 1 metabolism and with the percentage of change from run 1 to run 2. No significant run 2 correlations were observed. This is the first study to measure test-retest variability in cerebral glucose metabolism in a large sample of young normal subjects. It demonstrates that the deoxyglucose method yields low intrasubject variability and high stability over a 24-h period.

Behavior of mother rats in conflict tests sensitive to antianxiety agents.

Previous studies of freezing and open-field activity have demonstrated that lactating rats are less fearful or less anxious than nonpregnant ones. The purpose of this investigation was to observe the behavior of mother rats in conflict tests, which are frequently used in studies on the neurobiology of anxiety. In the punished drinking test, in which licking from a water spout is punished by electric shocks, mothers (observed on Day 1 postpartum following 24 hr of water deprivation) were found to drink more than virgins. Mothers (Day 1 postpartum) also consumed more food than controls in an unfamiliar open field. In contrast, no difference between mothers (Day 5 postpartum) and virgins was present in the exploration of an electrified shock probe. The largest maternal anticonflict effects in the drinking and feeding tests were recorded when the females were tested with their pups. Increased punished drinking was also observed in virgin rats treated with the anxiolytic benzodiazepine midazolam. Water-deprived virgins and mothers did not differ in the shock titration test, a result suggesting that diminished pain reactivity was unlikely to account for the increased punished drinking in mothers. Moreover, females in late pregnancy, which are hypoalgesic (Gintzler, 1980), did not lick more than virgins in the punished drinking test. Following 24 hr of water deprivation, unpunished drinking was higher in lactating females than in virgins, so the increased acceptance of punishment by mothers might have been due to their being more thirsty than virgins.(ABSTRACT TRUNCATED AT 250 WORDS)

Biogenic monoamine turnover in discrete rat brain regions is correlated with conditioned emotional response and its conditioning history.

The content and turnover of dopamine, norepinephrine and 5-hydroxytryptamine (serotonin), and the content of their respective major metabolites were evaluated in 19 discrete brain areas of rats exposed to conditioned emotional response (CER), and in control groups which received either equivalent yoked shock (shock only) or compound stimulus presentation (tone only). On test day, CER animals suppressed responding and exhibited forms of emotional behavior after presentation of the conditioned stimulus (CS); while shock only and tone only control groups, and CER animals which received an acute dose of diazepam prior to testing, did not suppress. Few changes were observed in content of the biogenic amines or their metabolites, suggesting that the behavioral manipulations were acting within normal physiological limits. On the other hand, numerous changes were observed in the utilization of the 3 biogenic monoamines, which were correlated with the conditioning-anxiety (comparisons of CER vs shock only) and the shock history (comparison of shock only vs tone only). These observations are consistent with putative neural pathways in the frontal cortex, septum, nucleus accumbens, amygdala, striatum, hippocampus and brain stem (which utilize specific monoamines), and with discrete brain areas which have been implicated in classical conditioning and CER-related phenomena. These observations suggest roles for biogenic monoamines in mediating or responding to the classical conditioning and emotional components of the paradigm.

Autoradiographic and quantitative study of benzodiazepine-binding sites in human hippocampus.

Benzodiazepine-binding sites were studied on frozen sections of 5 human hippocampi, using autoradiographic and biochemical techniques. The affinity, density, distribution and heterogeneity (two types) of sites were investigated using [3H]flunitrazepam as a ligand, clonazepam or C1 218872 as displacing agents. The autoradiographic images evidence a differential distribution of the binding sites in the histologic layers of the hippocampus. Subtypes I and II coexist in the same proportion in the three layers exhibiting the highest densities of binding sites (stratum granulosum and pyramidale, deep layer of stratum radiatum). The Kd, Bmax and Ki values found here are analogous to those described in animal studies, but the anatomical distribution of the sites in human hippocampus seems to differ slightly from that previously described in that of the rat.

Animal models of chronic anxiety and "fearlessness".

Three behavioral animal models have been described: a feline and a rodent model of chronic anxiety, and a rodent model of "fearless" behavior. The models have been obtained by pre- or perinatal exposure to diazepam (DZ) or RO 15-1788 which produced enduring postnatal deficits or enrichment, respectively, of brain benzodiazepine (BDZ) receptors. The receptor-deficient one-year-old cat progenies showed hyperarousal, unabated restless behavior, delayed acquisition of instrumentally conditioned behavior, bizarre escape responses and absence or reduced alpha-like EEG activity. The receptor-deficient rat progencies, studied at the age of 5-6 months, showed a reduction of time spent in deep slow wave sleep, and inability to habituate to novel environment, such as the radial arm maze. In the maze, the behavior of these progenies was characterized by delayed and incomplete exploratory activity often terminated by sudden escape, numerous fecal deposits and significantly more frequent than normal errors of "working memory." On the other hand, in all aspects, the receptor-enriched progenies were superior to the control animals as well as to the receptor-deficient group, particularly when the animals were challenged by novel and "intimidating" visual and/or auditory stimuli. In addition, 12 out of 51 receptor-deficient rats reared for 18 months developed mammary fibroadenomas, while no such tumors were found in the group of 44 vehicle-exposed control animals. Increased density and affinity of BDZ brain receptors was also observed after adult rats were treated with RO 15-1788 administered water for 7 or 14 days.

Plasma beta-endorphin, pain thresholds and anxiety levels across the human menstrual cycle.

Nine normally cycling women and seven other women employing oral contraception were tested during five phases (menstrual, follicular, ovulatory, luteal and premenstrual) of their menstrual cycle. The procedure consisted of administration of an anxiety inventory and determination of pain detection and pain thresholds in response to electric shock and the cold pressor task. Venipunctures were also performed and the plasma of normally menstruating women later assayed for beta-endorphin. Analyses revealed that the variance but not the mean levels in peripheral beta-endorphin levels significantly differed (p less than 0.01) across the menstrual cycle with the greatest amount of variance found during the ovulatory phase and the least during the luteal phase. The high variance during the period around ovulation was due to several subjects having extremely elevated beta-endorphin levels which possibly may have resulted from the occurrence of ovulation. Furthermore, a significant positive correlation between anxiety levels and beta-endorphin levels was found only during the menstrual phase. The absence of findings concerning cyclic variation in pain thresholds is contrary to earlier reports and indicates that such a phenomenon may be dependent upon the paradigm employed.

PIP: 9 mormally cycling women and 7 other women employing oral contraceptives (OCs) were tested during 5 phases (menstrual, follicular, ovulatory, luteal, and premenstrual) of their menstrual cycle. An anxiety inventory was administered and pain detection and pain thresholds in response to electric shock and the cold pressor task were determined. Venipunctures were also performed and the plasma of normally menstruating women later assayed for beta-endorphin. Analyses revealed that the variance but the not mean levels in peripheral beta-endorphin levels differed significantly (p0.01) across the menstrual cycle with the greatest amount of variance found during the ovulatory phase and the least during the luteal. The high variance during the period around ovulation was due to several subjects having extremely elevated beta-endorphin levels; this may have resulted from the occurrence of ovulation. Furthermore, a significant positive correlation between anxiety levels and beta-endorphin levels was found only during the menstrual phase. The absence of findings concerning cyclic variation in pain thresholds is contrary to earlier reports and indicates that such a phenomenon may be dependent on the paradigm employed.

Behavior control over aversive events: does control that requires effort reduce anxiety and physiological arousal?

Although it has been suggested that the ability to control (avoid) an aversive event will reduce arousal, it may be that the effort associated with exercising the control will offset the arousal reduction associated with avoidance. To determine whether the amount of effort required to control an aversive event influenced the amount of anxiety and physiological arousal associated with the aversive event, 89 subjects participated in a 3 (unavoidable threat, avoidable threat, no threat) X 2 (high-effort task performance, low-effort task performance) X 2 (anticipation period, performance period) factorial experiment. The results indicated that (a) the aversive event (threat of electrical shock) increased subjects' anxiety and physiological arousal; (b) exercising control was effective for decreasing subjects' anxiety to the non-threat level but only when low effort was required; (c) the prospect of control decreased subjects' physiological arousal to the no-threat level while the subjects were waiting to exercise control over the aversive event; however, (d) while actually exercising the control, subjects showed high physiological arousal like that of subjects who could not control the event. These findings impose important qualifications on the speculations concerning the influence of control.

Oral imagery and autonomic arousal in social isolation.

Psychoanalytic theory suggests that the presence of others reduces anxiety in those with oral-dependent needs. Electrodermal activity of male subjects high and low on Rorschach oral-dependent responses was monitored in one of three conditions while the subject was in a soundproof chamber for 40 minutes: alone with no task; alone working on a clerical task; and together with a male confederate, both working independently on the clerical task. Oral-dependent subjects placed in the chamber with the confederate showed fewer electrodermal increase over time than orals sitting alone or nonorals either alone or with the confederate (p less than .001). On the clerical task there was a strong main effect of orality, with nonorals showing more accuracy than orals (p less than .03).

A method to elicit aggressive feelings and behaviour via provocation.

A technique is described which elicits hostility via provocation in a competitive reaction time task incorporating a predetermined failure rate of 50%. When the subject loses he is exposed to a white noise which increases in intensity through the experiment. When he wins he is able to administer one of 8 levels of noise to his opponent. Heart rate and skin conductance level and fluctuations were monitored throughout the experiment. Self-ratings of mood, aggression and anxiety were completed both pre and post task. It was found that the task elicited hostility which could be measured behaviourally, physiologically and emotionally.

5HT2 receptors, depression and anxiety.

The distinction between non-psychotic repressive illness and anxiety states is blurred. Large scale trials in the neuroses indicate that benzodiazepines are ineffective in depression, and transiently and partially effective in anxiety. In contrast, tricyclic antidepressants are effective in both. All effective antidepressants decrease 5HT2 receptors number and this may mediate antidepressant efficacy. Our studies indicate that reduction of 5HT2 relative to 5HT1 neurotransmission would reverse the neuroendocrine abnormalities we have described in depression. Reduced 5HT2 neurotransmission may also be a mechanism of anxiolytic action in view of 5HT theories of punishment. There is clinical evidence for anxiolytic and antidepressant action of selective 5HT2 antagonists.

Frequency as a moderating variable in self-report measures of negative cognition.

Based on responses to the Distressing Thoughts Questionnaire, subjects' most frequent depressive and anxious cognitions were selected and compared with representative low frequency thought statements. The high frequency cognitions were more emotionally intense, uncontrollable and unacceptable than the low frequency thoughts. Although high frequency anxious items were rated as more frequent than high frequency depressive statements, no differences were evident in emotional intensity and controllability. Furthermore thoughts of loss and failure were specifically predictive of dysphoria only when high frequency cognitive items were utilized. The implications of these findings for cognitive assessment issues were discussed.

The effect of (induced) maternal emotions on fetal behaviour: a controlled study.

In ten healthy near-term pregnant women the effect of induced maternal emotions on fetal motor behaviour was studied. Emotions were induced by showing a film of a normal delivery. Fetal behaviour was recorded by means of real-time ultrasound observations of general movements and eye movements and by fetal heart rate monitoring. The observations had a duration of 2 h. The data were compared with those obtained during a 2-h control period, which took place the day before (n = 5) or after the study period (n = 5). Maternal emotions (induced) were measured by means of psychological tests. No effects on fetal motor activity or on behavioural state organization could be found as a result of this film. There was, however, a significant positive correlation (P less than 0.01) between the mean level of anxiety of the women and the motor activity of the fetuses.

Minor tranquilizers and brain defense systems.

In this article the participation of different brain neuron systems in the integration of fear responses, and in the anti-anxiety action of minor tranquilizers (MT) is discussed. As necessary background, the molecular mechanisms of MT action disclosed by recent neurochemical research are briefly described. The reviewed evidence suggests that MT decrease anxiety by impairing the functioning of brain neuron systems integrating defensive behavior. These systems are the septo-hippocampal system, together with its afferent mono-aminergic input from the rostral brain stem, which commands behavioral inhibition arising in situations involving threat of punishment or frustration. In addition, the brain aversive system comprising the dorsal periaqueductal gray matter, the periventricular gray matter and the amygdala integrates the active defense patterns of fight or flight as well as elaborates aversive motivation. The depressant action of MT upon both defense systems may be primarily due to facilitation of neurotransmission mediated by gamma-aminobutyric acid (GABA).

Stress and workload in pilots.

Several studies have highlighted the increase in physiological activity which occurs in pilots during flight and especially during takeoffs and landings. For example, it has been clearly demonstrated that pilots' heart rates increase during the landing approach to reach a peak at or just before touchdown. These changes have been attributed to workload and to psychological or emotional stress. This paper examines a number of test pilots' heart rate responses recorded during various flight trials involving different types of aircraft. Examples include ramp takeoffs in a VTOL fighter, automatic landings in fog, supersonic flight through monsoon rain, and a sortie in which the pilot developed acute appendicitis. It is concluded that heart rate responses in experienced pilots are influenced almost entirely by workload-related factors and not by emotional stressors, such as risk and anxiety. Because of the emotional overtones of the word "stress," it is suggested that the term workload should be used when referring to the reason for increased cardiovascular activity of pilots.

Physiological measurements in phobic and obsessional disorders.

The various physiological measurements which can be made in obsessional and phobic disorders are described. Useful information can be obtained about the effects of acute stress and the changes that medication can produce in anxious patients and the clinical progress of behaviour therapy can be monitored. When physiological measurements are made it is important to record the emotional state of the patient simultaneously so that the level of physiological arousal is related to the subjective experience of the patient.

[The simplest form of emotional-motor reaction in man]. / Prosteishaia forma émotsional'no-motornogo reagirovaniia cheloveka.

In the present paper, human startle reaction (SR) characteristics were estimated by the amplitude of eye-lid reflex and extent of monosynaptic H-reflexes increase. SR depended not only on the parameters of sound stimulation (strength, unexpectedness) but also on the subject's functional state (attention, emotional background). Differences are given of the SR parameters from the orienting reaction. It is supposed that SR is an independent form of emotional-motor reaction of an adaptive character.

[Experimental studies of the "anticipation stress" syndrome]. / Eksperimental'noe issledovanie sindroma "stress ozhidaniia"

Bioelectrical activity of the limbic structures (amygdala, dorsal and ventral hippocampus), the cortex and etologic responses during the formation of emotional stress of negative modality, were studied on Wistar rats under conditions of continuous many-hour neurotization. The presentation of stimuli according to a strict temporal shceme produced profound changes in the activity of the investigated cerebral structures and of the motor sphere. The established sequence in the involvement of the limbico-neocortical complex in the process of emotional stress with parallel use of the conditioned reflex to time, points to the participation of the hippocampus in the prediction of events (hippocampus leads to amygdala leads to cortex). Stages of biological reactions have been revealed, corresponding to the stages of Selye's adaptation syndrome. Stages of anxiety, adaptation and exhaustion proceeded with features characteristic of each group of animals ("inhibitory type", "steady type", "excitatory type", "overexcitatory type") and peculiar bioelectrical and etological responses.

[Neurophysiologic organization of the pathologic craving for alcohol]. / Neirofiziologicheskaia organizatsiia patologicheskogo vlecheniia k alkogoliu.

The authors examined the functional shifts occurring at various levels of the non-specific activation system of the brain in positive (euphoria in the state of alcoholic intoxication) and negative (anxiety in the period of abstinence) emotional states. An analysis of the EEG, as well as the EMG of the articulation muscles gives one grounds to suppose that the euphoria is accompanied by a weakening of the activation on the part of mesencephalon, and, at the same time, an intensification of the diencephalo-limbic activation processes. On the contrary, the anxiety is accompanied by mesencephalic hyperactivation which is, probably, eliminated after taking a dose of alcohol.