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