Intrinsic brain activity in health and disease

The main part of the brain’s energy need is to support housekeeping functions and internal information processing, regardless of external tasks. Cognitive brain imaging, aimed at relating mental phenomena to neurophysiological processes, has conventionally investigated the brain activity induced by external stimuli. In contrast, resting state functional Magnetic Resonance Imaging (rs-fMRI) aims to characterize the spatiotemporal properties of the ongoing baseline brain activity.

In the projects constituting the current thesis, we have used rs-fMRI to investigate effects of neuropharamcological administrations, long-term physical exercise and to characterize central pain processing in rheumatic pain conditions. Study I is a randomized, cross sectional placebo study, in which healthy subjects were administered Parkinson medications (L-dopa), anxiolytics (oxazepam), or placebo. Our a priori hypothesis of preferential modulations of connectivity of brain regions with high density of target receptors was not confirmed. Instead, oxazepam was associated with increased connectivity of cardinal hubs within the default mode network, and interestingly, a decoupling of the amygdala. L-dopa, on the other hand, primarily decreased connectivity, particularly between amygdala and bilateral prefrontal gyri.

In studies II-IV we investigated rheumatic pain patients. In study II we compared a fibromyalgia (FM) cohort and healthy controls (HC) with regard to functional brain connectivity of particularly cerebral pain regions. Conducting both data driven independent component analysis (ICA) and seed correlation analysis (SCA), we observed a weaker coupling between pain regions and sensorimotor brain areas in the FM group. Across groups, pain sensitivity correlated with e.g. increased connectivity between insula and the posterior cingulate cortex.

Physical exercise is a potent reliever of FM symptoms. In study III, we investigated the effects a three months physical training intervention for FM patients. Following exercise, patients reported decreased symptom gravity, and the FM associated hyper-connectivity identified at baseline was partly normalized.

In study IV, we investigated the extent to which exposure to chronic pain for patients with rheumatoid arthritis (RA) was reflected in functional connectivity of pain regions. Overall, RA patients had elevated connectivity, particularly between frontal midline areas and bilateral sensorimotor cortex.

Taken together, we have shown that short-term neuropharmachological interventions, a three months physical exercise intervention as well as long-term rheumatic pain exposure, all are accompanied by changes in intrinsic brain activity. Although the functional significance of the observed group differences in connectivity warrants further investigations, the evidences presented here support the notion that rs-fMRI could prove useful for diagnosing neuropsychiatric conditions and evaluating interventions in the future.

List of scientific papers

I. Flodin P, Gospic K, Petrovic P, Fransson P. (2012). Effects of L-dopa and oxazepam on resting-state functional magnetic resonance imaging connectivity : a randomized, cross-sectional placebo study. Brain Connectivity, 2:246-53.
https://doi.org/10.1089/brain.2012.0081

II. Flodin P, Martinsen S, Löfgren M, Bileviciute-Ljungar I, Kosek E, Fransson P. (2014). Fibromyalgia is associated with decreased connectivity between pain and sensorimotor brain areas. Brain Connectivity. 4:587-94.
https://doi.org/10.1089/brain.2014.0274

III. Flodin P, Martinsen S, Mannerkorpi K, Löfgren M, Bileviciute-Ljungar I, Kosek E, Fransson P. (2015). Normalization of aberrant resting state functional connectivity in fibromyalgia patients following a three months physical exercise therapy. NeuroImage: Clinical. [Accepted]
https://doi.org/10.1016/j.nicl.2015.08.004

IV. Flodin P, Martinsen S, Altawil R, Waldheim E, Lampa J, Kosek E, Fransson P. Intrinsic brain connectivity in chronic pain : a resting- state fMRI study in patients with rheumatoid arthritis. [Submitted]