Alcohol induced region-dependent alterations of hemodynamic response: implications for the statistical interpretation of pharmacological fMRI studies

Abstract

Worldwide, ethanol abuse causes thousands of fatal accidents annually as well as innumerable social dysfunctions and severe medical disorders. Yet, few studies have used the blood oxygenation level dependent functional magnetic resonance imaging method (BOLD fMRI) to map how alcohol alters brain functions, as fMRI relies on neurovascular coupling, which may change due to the vasoactive properties of alcohol. We monitored the hemodynamic response function (HRF) with a high temporal resolution. In both motor cortices and the visual cortex, alcohol prolonged the time course of the HRF, indicating an overall slow-down of neurovascular coupling rather than an isolated reduction in neuronal activity. However, in the supplementary motor area, alcohol-induced changes to the HRF suggest a reduced neuronal activation. This may explain why initiating and coordinating complex movements, including speech production, are often impaired earlier than executing basic motor patterns. Furthermore, the present study revealed a potential pitfall associated with the statistical interpretation of pharmacological fMRI studies based on the general linear model: if the functional form of the HRF is changed between the conditions data may be erroneously interpreted as increased or decreased neuronal activation. Thus, our study not only presents an additional key to how alcohol affects the network of brain functions but also implies that potential changes to neurovascular coupling have to be taken into account when interpreting BOLD fMRI. Therefore, measuring individual drug-induced HRF changes is recommended for pharmacological fMRI.

Finding a way in: A review and practical evaluation of fMRI and EEG for detection and assessment in disorders of consciousness

“…A growing body of evidence shows that many diseases and pathologies -including brain injuries -alter neurovascular coupling and change BOLD signal without necessarily affecting neuronal function Gsell et al, 2000;Krainik et al, 2005;Lindauer et al, 2010;Sakatani et al, 2003Sakatani et al, , 2007. In the same vein, we must also consider that patients with severe brain injuries are usually on several medications, which can also influence neurovascular coupling (Bruhn et al, 2001;Luchtmann et al, 2010;Pattinson et al, 2007;Reinhard et al, 2010). We can attribute changes in BOLD signal to changes in neural activity if and only if signalling and vascular reactivity are not altered; and we can compare between groups (e.g., patients and controls) only if these properties are the same in both groups.…”

Alcohol affects brain functional connectivity and its coupling with behavior: greater effects in male heavy drinkers

“…11–14 The opposite effects of acute alcohol on CBF and CMRglc, on one hand reflect alcohol’s vasoactive effects 15 , and on the other hand reflect the use of alternative energy sources for brain metabolism (e.g., alcohol’s metabolite acetate). 16,17 Specifically, recent work has suggested that biphasic vasoactive properties of alcohol 15 may disrupt the coupling between neuronal activity and CBF. 16 In relation to the association between CMRglc and brain activity during intoxication, our work has suggested that alcohol-induced decreases in glucose metabolism are concurrent with brain-wide increases in acetate metabolism.…”

“…16,17 Specifically, recent work has suggested that biphasic vasoactive properties of alcohol 15 may disrupt the coupling between neuronal activity and CBF. 16 In relation to the association between CMRglc and brain activity during intoxication, our work has suggested that alcohol-induced decreases in glucose metabolism are concurrent with brain-wide increases in acetate metabolism. 17 The acetate content in plasma increases during alcohol intoxication.…”

Electrical Tongue Stimulation Normalizes Activity Within the Motion-Sensitive Brain Network in Balance-Impaired Subjects as Revealed by Group Independent Component Analysis

“…The benefits of this approach become clear when investigating subjects with processes that may modify the local HRF or when analyzing data from rest scans (Brown et al, 2001;Moritz et al, 2005;Quigley et al, 2002). It is known that many factors such as age, respiration, disease states, and medications can all affect the shape of the HRF (Bonakdarpour et al, 2007;Luchtmann et al, 2010). ICA can identify temporal signals and spatial networks without utilizing any preformed assumptions about neural responses.…”