Anxiety, cerebral blood flow and neuropsychological complaints

The studies described in this document are related to the FWO-project entitled “Hyperventilation, Cerebral Blood Flow and Pseudoneurological Complaints”. The aim is to investigate cerebral blood flow (CBF) and pseudoneurological complaints (or neuropsychological complaints, NPC) in relationship to anxiety, hyperventilation and learning. Because NPC - a variety of complaints, such as lightheadedness, dizziness, and tiredness that occur in the absence of a medical condition - are related to stress and anxiety and have a higher prevalence in several psychiatric conditions such as anxiety disorders, this project focuses on the possible pathways between NPC and stress and anxiety. A first possible pathway implies hyperventilation. Hyperventilation induces cerebral vasoconstriction as well as a pattern of symptoms that overlaps with NPC (e.g. lightheadedness). Hyperventilation has been proposed as an explanation for NPC, but has subsequently been discredited after it was found that reductions in PaCO2 did not temporally coincide with the symptom reports. However, a learning-based laboratory model for NPC which was developed in this research group may overcome this critique. Whereas the model originally uses CO2 enriched air as a US to evoke symptoms in a differential conditioning paradigm, we use hyperventilation (i.e., hypocapnia) instead of CO2 in order to expand the model to the learning of complaints in relation to stress and anxiety. Several episodes of anxiety/stress-induced hyperventilation would then act as learning episodes causing NPC to be associated with non-causally related cues (CSs). In addition, we aim to investigate whether repeated hyperventilation experiences can give rise to Pavlovian conditioning of cerebral vasomotor responses. This would provide a neurological explanation for NPC. A second pathway implies processes related to anxiety and sympathetic activation, and its effects on CBF. The importance of sympathetically induced CBF changes in the context of anxiety is underlined by the fact that both NPC and anomalies in cerebral blood flow have been found in patients with anxiety disorders. Despite these findings, limited attention has been devoted in psychiatry to the relationship between anxiety and anxiety disorders on the one hand and CBF on the other hand. In this project, we want to further investigate this relationship by inducing short-lived anxiety states in healthy subjects and document the CBF response and complaints. The current project investigates both pathways to elucidate the relationship between anxiety and stress on the one hand and global cerebral blood flow changes and NPC on the other hand. Two pilot studies and three experiments are discussed. The pilot studies were set up to investigate the feasibility of Transcranial Doppler (TCD). Experiment 1 investigated differential conditioning of NPC and CBF responses in response to hyperventilation and found several NPC (such as lightheadedness) to be easily acquired through conditioning, without any conditioned changes in CBF. In the subsequent two studies we found anxiety, induced by a threat-of-shock paradigm, to induce changes in global CBF. Furthermore, we found the effect of anxiety to be dependent on manipulated levels of CO2. Future directions based on these findings will be laid out.status: publishe

Feeling lightheaded: the role of cerebral blood flow

Objective: The main aims of this study were a) to investigate the relationship between lightheadedness and cerebral blood flow velocity (CBFv) during hyperventilation-induced hypocapnia, and b) to investigate whether and why the relationship between lightheadedness and CBFv may change after several episodes of this sensation. Methods: Three hypocapnic and three normocapnic overbreathing trials were administered in a semirandomized order to healthy participants (N = 33). Each type of breathing trial was consistently paired with one odor. Afterward, participants were presented each odor once in two spontaneous breathing and in two normocapnic overbreathing trials. CBFv in the right middle cerebral artery was measured by transcranial Doppler ultrasonography (TCD). Also breathing behavior and self-reported lightheadedness were measured continuously. Each trial was followed by a symptom checklist. Results: Self-reported lightheadedness was closely related to changes in CBFv in the hypocapnic overbreathing trials. During the subsequent normocapnic trials, however, participants experienced more lightheadedness and "feeling unreal" to the odor that had previously been paired with hyperventilation-induced hypocapnia. These complaints were not accompanied by changes in end-tidal CO(2) nor in CBFv. Conclusions: The results show that lightheadedness is associated with changes in CBFv but that after a few episodes, the underlying mechanism for this symptom may shift to perceptual-cognitive processes. These findings may help to understand why lightheadedness occurs during emotional distress and panic. In addition, altered cerebral blood flow is unlikely to play a primary precipitating role in recurrent symptoms of lightheadedness.status: publishe

Defense reactions to interoceptive threats: a comparison between loaded breathing and aversive picture viewing

Human fear research has mostly applied exteroceptive stimuli to induce fear. Interoceptive sensations however can also be very threatening and play a major role in a number of anxiety disorders. In this study, we compared affective responses to inspiratory resistive loads with those to aversive pictures. During repeated administrations of two loads, a light and a moderate one, and five aversive pictures we measured electrodermal activity, startle blink responses, subjective fear and ratings on valence, arousal and dominance. Results indicate that loads evoke affective reactions comparable or stronger than those evoked by the pictures. Startle data did not follow this pattern with an absence of startle potentiation during the moderate load, suggesting that fear potentiated startle does not occur when the background aversive stimulus is of an interoceptive nature.status: publishe

Acquired lightheadedness in response to odors after hyperventilation

OBJECTIVE: This study aimed to investigate whether lightheadedness in response to odors could be acquired through previous associations with hyperventilation-induced hypocapnia. METHODS: Diluted ammonia and acetic acid served as conditional odor cues (CSs) in a differential associative learning paradigm. Hyperventilation-induced hypocapnia (unconditional stimulus [US]) was used to induce lightheadedness. In a training phase, participants (n = 28) performed three hypocapnic and three normocapnic overbreathing trials of 60 seconds each. One odor was consistently paired with the hypocapnic overbreathing (CS+); the other (control) odor was paired with normocapnic overbreathing (CS-). In the test phase, each odor was presented once during spontaneous breathing and once during normocapnic overventilation. Lightheadedness was assessed online during each breathing trial, which was followed by an extensive hyperventilation symptom checklist. Fractional end-tidal CO2, breathing frequency, and inspiratory volume were measured throughout the experiment. RESULTS: In the test phase, participants experienced lightheadedness more quickly in response to the odor that had been paired with hypocapnic overbreathing compared with the control odor. They also scored higher on the symptom "feeling unreal." CONCLUSION: Lightheadedness in response to odors can be acquired easily. The present results may help to elucidate the paradox that both avoidance and exposure to chemicals seem to be effective in reducing symptoms in idiopathic environmental illness.Onderzoeksgroep voor Stress, gezondheid en welzijn. Afdeling Pneumologie.status: publishe