A consensus protocol for functional connectivity analysis in the rat brain.

Task-free functional connectivity in animal models provides an experimental framework to examine connectivity phenomena under controlled conditions and allows for comparisons with data modalities collected under invasive or terminal procedures. Currently, animal acquisitions are performed with varying protocols and analyses that hamper result comparison and integration. Here we introduce StandardRat, a consensus rat functional magnetic resonance imaging acquisition protocol tested across 20 centers. To develop this protocol with optimized acquisition and processing parameters, we initially aggregated 65 functional imaging datasets acquired from rats across 46 centers. We developed a reproducible pipeline for analyzing rat data acquired with diverse protocols and determined experimental and processing parameters associated with the robust detection of functional connectivity across centers. We show that the standardized protocol enhances biologically plausible functional connectivity patterns relative to previous acquisitions. The protocol and processing pipeline described here is openly shared with the neuroimaging community to promote interoperability and cooperation toward tackling the most important challenges in neuroscience.

A functional magnetic resonance imaging examination of audiovisual observation of a point-light string quartet using intersubject correlation and physical feature analysis.

We use functional Magnetic Resonance Imaging (fMRI) to explore synchronized neural responses between observers of audiovisual presentation of a string quartet performance during free viewing. Audio presentation was accompanied by visual presentation of the string quartet as stick figures observed from a static viewpoint. Brain data from 18 musical novices were obtained during audiovisual presentation of a 116 s performance of the allegro of String Quartet, No. 14 in D minor by Schubert played by the 'Quartetto di Cremona.' These data were analyzed using intersubject correlation (ISC). Results showed extensive ISC in auditory and visual areas as well as parietal cortex, frontal cortex and subcortical areas including the medial geniculate and basal ganglia (putamen). These results from a single fixed viewpoint of multiple musicians are greater than previous reports of ISC from unstructured group activity but are broadly consistent with related research that used ISC to explore listening to music or watching solo dance. A feature analysis examining the relationship between brain activity and physical features of the auditory and visual signals yielded findings of a large proportion of activity related to auditory and visual processing, particularly in the superior temporal gyrus (STG) as well as midbrain areas. Motor areas were also involved, potentially as a result of watching motion from the stick figure display of musicians in the string quartet. These results reveal involvement of areas such as the putamen in processing complex musical performance and highlight the potential of using brief naturalistic stimuli to localize distinct brain areas and elucidate potential mechanisms underlying multisensory integration.

Anxiety enhances pain in a model of osteoarthritis and is associated with altered endogenous opioid function and reduced opioid analgesia.

INTRODUCTION: Negative affect, including anxiety and depression, is prevalent in chronic pain states such as osteoarthritis (OA) and associated with greater use of opioid analgesics, potentially contributing to present and future opioid crises. OBJECTIVES: We tested the hypothesis that the interaction between anxiety, chronic pain, and opioid use results from altered endogenous opioid function. METHODS: A genetic model of negative affect, the Wistar-Kyoto (WKY) rat, was combined with intra-articular injection of monosodium iodoacetate (MIA; 1 mg) to mimic clinical presentation. Effects of systemic morphine (0.5-3.5 mg·kg-1) on pain behaviour and spinal nociceptive neuronal activity were compared in WKY and normo-anxiety Wistar rats 3 weeks after MIA injection. Endogenous opioid function was probed by the blockade of opioid receptors (0.1-1 mg·kg-1 systemic naloxone), quantification of plasma ß-endorphin, and expression and phosphorylation of spinal mu-opioid receptor (MOR). RESULTS: Monosodium iodoacetate-treated WKY rats had enhanced OA-like pain, blunted morphine-induced analgesia, and greater mechanical hypersensitivity following systemic naloxone, compared with Wistar rats, and elevated plasma ß-endorphin levels compared with saline-treated WKY controls. Increased MOR phosphorylation at the master site (serine residue 375) in the spinal cord dorsal horn of WKY rats with OA-like pain (P = 0.0312) indicated greater MOR desensitization. CONCLUSIONS: Reduced clinical analgesic efficacy of morphine was recapitulated in a model of high anxiety and OA-like pain, in which endogenous opioid tone was altered, and MOR function attenuated, in the absence of previous exogenous opioid ligand exposure. These findings shed new light on the mechanisms underlying the increased opioid analgesic use in high anxiety patients with chronic pain.