The effect of transcutaneous vagus nerve stimulation on fear generalization and subsequent fear extinction.

Fear overgeneralization is thought to be one of the cardinal processes underlying anxiety disorders, and a determinant of the onset, maintenance and recurrence of these disorders. Animal studies have shown that stimulating the vagus nerve (VNS) affects neuronal pathways implicated in pattern separation and completion, suggesting it may reduce the generalization of a fear memory to novel situations. In a one-day study, 58 healthy students were subjected to a fear conditioning, fear generalization, and fear extinction paradigm. Participants were randomly assigned to receive either transcutaneous auricular VNS (tVNS; final N = 29) or sham stimulation (final N = 29) during the generalization and extinction phases. tVNS did not affect fear generalization, as reflected by US expectancy ratings and fear potentiated startle responses. However, participants who received tVNS reported lower US expectancy ratings to the CS+ during the extinction phase, possibly reflecting a stronger declarative extinction of fear. No effects of tVNS on fear potentiated startle responses during extinction were found. The pattern of findings regarding extinction of declarative fear suggest a facilitating effect of tVNS.

Mixed evidence for the potential of non-invasive transcutaneous vagal nerve stimulation to improve the extinction and retention of fear.

Extinction memories are fragile and their formation has been proposed to partially rely on vagus nerve activity. We tested whether stimulating the auricular branch of the vagus (transcutaneous VNS; tVNS) accelerates extinction and reduces spontaneous recovery of fear. Forty-two healthy students participated in a 3-day fear conditioning study, where we tested fear acquisition (day 1), fear extinction (day 2) and the retention of the extinction memory (day 3). During extinction, participants were randomly allocated to receive tVNS or sham stimulation concurrently with each CS presentation. During the acquisition and retention phases, all participants received sham stimulation. Indexes of fear included US-expectancy, startle blink EMG and skin conductance responses. Results showed successful acquisition and extinction of fear in all measures. tVNS facilitated the extinction of declarative fear (US expectancy ratings), but did not promote a stronger retention of the declarative extinction memory. No clear effects of tVNS on extinction and retention of extinction were found for the psychophysiological indexes. The present findings provide tentative indications that tVNS could be a promising tool to improve fear extinction and call for larger scale studies to replicate these effects.

[Cognitive-behavioural therapy for primary insomnia: effectiveness in a clinical setting]. / Cognitieve gedragstherapie voor primaire insomnia: effectiviteit in een klinische setting.

BACKGROUND: The effectiveness of cognitive behavioural therapy for insomnia (cbt-i) has been demonstrated in randomised controlled trials (rct's) with primary insomnia patients and, more recently, with comorbid insomnia patients. The clinical impact of the treatment is mainly on sleep quality and the use of medication and to a lesser extent on daytime functioning. So far there have been very few studies of the effectiveness of cbt-i in clinical settings. AIM: To examine the effectiveness of cbt-i for primary insomnia via an uncontrolled prospective study in a clinical tertiary care setting. METHOD: We included 76 patients with primary insomnia, most of whom having been referred by their gp or medical specialist to the Leuven University Centre of Sleep, who followed a 6-week course of cbt-i as a group. Effects of cbt-i on primary and secondary outcome measures were studied. results cbt-i resulted in a significant improvement in all primary sleep variables such as sleep onset, sleep efficiency and sleep quality. The increase in total sleep time was less substantial, probably as a result of the specific sleep restriction guidelines. There was also a significant improvement on several secondary parameters, in particular dysfunctional cognitions, affective state, general health and use of medication. CONCLUSIONS: cbt-i has a significant impact on sleep quality, medication use and daytime functioning in primary insomniacs in a clinical tertiary care setting.

Medically unexplained dyspnea: psychophysiological characteristics and role of breathing therapy.

BACKGROUND: Medically unexplained dyspnea occurs commonly in medical settings and remains poorly understood. This study was conducted to investigate the psychophysiological characteristics of medically unexplained dyspnea and the efficacy of breathing retraining for these patients. METHODS: A group of patients with medically unexplained dyspnea were compared to patients with a variety of organic lung diseases and healthy subjects. In another group of patients, the influence of breathing therapy on complaints, anxiety, and breath-holding was evaluated for an average of 1.5 years. RESULTS: Patients with medically unexplained dyspnea reported more intense dyspnea than patients with a variety of organic lung diseases. Additionally, they were anxious and presented a broad range of symptoms in daily life and under challenge, for instance voluntary hyperventilation. More than one third of them qualified for panic disorder. They had shorter breath-holding time at rest, less increase in breath-holding time and higher chances of showing a "paradoxical" decrease of breath-holding time after hyperventilation. A combination of PaO2, forced expiratory volume in one second (FEV1), and anxiety measures distinguished them from organic dyspnea. Breathing retraining profoundly improved their symptoms and decreased the level of state and trait anxiety. Moreover, they better tolerated the voluntary hyperventilation and the symptoms induced were also markedly decreased after therapy. Breath-holding time was prolonged and PetCO2 in a representative group of patients increased. CONCLUSIONS: Patients with medically unexplained dyspnea appear to have the feature of a "psychosomatic" patient: an anxious patient with a wide variety of symptoms of different organ systems that do not have an organic basis. They can be distinguished from organic dyspnea using a small set of physiological and psychological measures. Breathing retraining turns out to be an effective therapy for those "difficult to treat patients".

Critical conditions for hyperventilation responses. The role of autonomic response propositions during emotional imagery.

Hyperventilation is often conceived of as part of a fight-or-flight response, triggered by situations with high arousal and negative valence. However, a previous study using emotional imagery found hyperventilation responses during imagery of high-arousal scenes regardless of their valence. Those imagery scripts contained suggestions of autonomic activity, which may have partly induced or enhanced the hyperventilatory responsivity. The present study used four emotional scripts--depicting relaxing, fearful, depressive, and pleasant situations--without suggestions of autonomic or respiratory responses. After each imagery trial, participants rated their imagery for valence, arousal, and vividness. Fractional end-tidal carbon dioxide (FetCO2), inspiratory and expiratory time, tidal volume, and pulse rate were measured in a non-intrusive way. Results showed significant FetCO2 drops during the fearful and pleasant scripts. However, this effect was much smaller compared to imagery scripts with autonomic response propositions. Participants imagining scripts without autonomic response information found it harder to imagine the scripts vividly and reported lower levels of subjective arousal.

Hyperventilation beyond fight/flight: respiratory responses during emotional imagery.

Hyperventilation (HV) is often considered part of a defense response, implying an unpleasant emotion (negative valence) combined with a strong action tendency (high arousal). In this study, we investigated the importance of arousal and valence as triggers for HV responses. Forty women imagined eight different scripts varying along the arousal and valence dimensions. The scripts depicted relaxation, fear, depressive, action, and desire situations. After each trial, the imagery was rated for valence, arousal, and vividness. FetCO2, inspiratory and expiratory time, tidal volume, and pulse rate were measured in a nonintrusive way. FetCO2 drops and decreases in inspiratory and expiratory time occurred in all but the depressive and the relaxation scripts, suggesting that a defense conceptualization of hyperventilation is not always appropriate.

Hyperventilation and attention: effects of hypocapnia on performance in a stroop task.

This study aimed to investigate the effect of hypocapnia on attentional performance. Hyperventilation, producing hypocapnia, is associated with physiological changes in the brain and with subjective symptoms of dizziness, concentration problems and derealization. In this study (N=42), we examined cognitive performance on a Stroop-like task, following either 3 min of hypocapnic or normocapnic overbreathing. Both overbreathing trials were run on separate days, each preceded by a baseline trial with the same task during normal breathing. More and other symptoms were reported after hypocapnia compared to normocapnia. Also, more errors were made and progressively slower reaction times (RT's) were observed during recovery from hypocapnia. These performance deficits were only found in participants characterized by apneas. The number of symptoms did not correlate with RT's or errors. The pattern of data suggested that hypoxia, as a result of apneas during recovery from hypocapnia, caused the cognitive performance deficit.

Generalization of acquired somatic symptoms in response to odors: a pavlovian perspective on multiple chemical sensitivity.

OBJECTIVE: Somatic symptoms that occur in response to odors can be acquired in a pavlovian conditioning paradigm. The present study investigated 1) whether learned symptoms can generalize to new odors, 2) whether the generalization gradient is linked to the affective or irritant quality of the new odors, and 3) whether the delay between acquisition and testing modulates generalization. METHODS: Conditional odor stimuli (CS) were (diluted) ammonia and niaouli. One odor was mixed with 7.4% CO2-enriched air (unconditional stimulus) during 2-minute breathing trials (CS+ trial), and the other odor was presented with air (CS- trial). Three CS+ and three CS- trials were conducted in a semirandomized order (acquisition phase). The test phase involved one CS+-only (CS+ without CO2) and one CS- test trial, followed by three trials using new odors (butyric acid, acetic acid, and citric aroma). Half of the subjects (N = 28) were tested immediately, and the other half were tested after 1 week. Ventilatory responses were measured during and somatic symptoms were measured after each trial. RESULTS: Participants had more symptoms in response to CS+-only exposures, but only when ammonia was used as the CS+. Also, generalization occurred: More symptoms were reported in response to butyric and acetic acid than to citric aroma and only in participants who had been conditioned. Both the selective conditioning and the generalization effect were mediated by negative affectivity of the participants. The delay between the acquisition and test phases had no effect. CONCLUSIONS: Symptoms that occur in response to odorous substances can be learned and generalize to new substances, especially in persons with high negative affectivity. The findings further support the plausibility of a pavlovian perspective of multiple chemical sensitivity.

Acquisition and extinction of somatic symptoms in response to odours: a Pavlovian paradigm relevant to multiple chemical sensitivity.

OBJECTIVES: Multiple chemical sensitivity is a poorly understood syndrome in which various symptoms are triggered by chemically unrelated, but often odorous substances, at doses below those known to be harmful. This study focuses on the process of pavlovian acquisition and extinction of somatic symptoms triggered by odours. METHODS: Diluted ammonia and butyric acid were odorous conditioned stimuli (CS). The unconditioned stimulus (US) was 7.4% CO2 enriched air. One odour (CS+) was presented together with the US for 2 minutes (CS+ trial), and the other odour (CS-) was presented with air (CS-trial). Three CS+ and three CS-exposures were run in a semi-randomised order; this as the acquisition (conditioning) phase. To test the effect of the conditioning, each subject then had one CS+ only--that is, CS+ without CO2--and one CS- test exposure. Next, half the subjects (n = 32) received five additional CS+ only exposures (extinction group), while the other half received five exposures to breathing air (wait group). Finally, all subjects got one CS+ only test exposure to test the effect of the extinction. Ventilatory responses were measured during and somatic symptoms after each exposure. RESULTS: More symptoms were reported upon exposure to CS+ only than to CS-odours, regardless of the odour type. Altered respiratory rate was only found when ammonia was CS+. Five extinction trials were sufficient to reduce the level of acquired symptoms. CONCLUSION: Subjects can acquire somatic symptoms and altered respiratory behaviour in response to harmless, but odorous chemical substances, if these odours have been associated with a physiological challenge that originally had caused these symptoms. The conditioned symptoms can subsequently be reduced in an extinction procedure. The study further supports the plausibility of a pavlovian conditioning hypothesis to explain the pathogenesis of MCS.