The influence of insulin on anticipation and consummatory reward to food intake: A functional imaging study on healthy normal weight and overweight subjects employing intranasal insulin delivery.

Aberrant responses within homeostatic, hedonic and cognitive systems contribute to poor appetite control in those with an overweight phenotype. The hedonic system incorporates limbic and meso-limbic regions involved in learning and reward processing, as well as cortical regions involved in motivation, decision making and gustatory processing. Equally important within this complex, multifaceted framework are the cognitive systems involved in inhibitory control and valuation of food choices. Regions within these systems display insulin receptors and pharmacologically increasing central insulin concentrations using intranasal administration (IN-INS) has been shown to significantly reduce appealing food cue responsiveness and also food intake. In this work we describe a placebo-controlled crossover pharmacological functional magnetic resonance imaging (fMRI) study that looks at how IN-INS (160 IU) affects anticipatory and consummatory responses to sweet stimuli and importantly how these responses differ between healthy normal weight and overweight male individuals. This work shows that age matched normal weight and overweight (not obese) individuals respond similarly to both the anticipation and receipt of sweet stimuli under placebo conditions. However, increased central insulin concentrations produce marked differences between groups when anticipating sweet stimuli within the prefrontal cortex and midbrain as well as observed differences in the amygdala during consummatory responses.

Revealing the mechanisms behind novel auditory stimuli discrimination: An evaluation of silent functional MRI using looping star.

Looping Star is a near-silent, multi-echo, 3D functional magnetic resonance imaging (fMRI) technique. It reduces acoustic noise by at least 25dBA, with respect to gradient-recalled echo echo-planar imaging (GRE-EPI)-based fMRI. Looping Star has successfully demonstrated sensitivity to the cerebral blood-oxygen-level-dependent (BOLD) response during block design paradigms but has not been applied to event-related auditory perception tasks. Demonstrating Looping Star's sensitivity to such tasks could (a) provide new insights into auditory processing studies, (b) minimise the need for invasive ear protection, and (c) facilitate the translation of numerous fMRI studies to investigations in sound-averse patients. We aimed to demonstrate, for the first time, that multi-echo Looping Star has sufficient sensitivity to the BOLD response, compared to that of GRE-EPI, during a well-established event-related auditory discrimination paradigm: the "oddball" task. We also present the first quantitative evaluation of Looping Star's test-retest reliability using the intra-class correlation coefficient. Twelve participants were scanned using single-echo GRE-EPI and multi-echo Looping Star fMRI in two sessions. Random-effects analyses were performed, evaluating the overall response to tones and differential tone recognition, and intermodality analyses were computed. We found that multi-echo Looping Star exhibited consistent sensitivity to auditory stimulation relative to GRE-EPI. However, Looping Star demonstrated lower test-retest reliability in comparison with GRE-EPI. This could reflect differences in functional sensitivity between the techniques, though further study is necessary with additional cognitive paradigms as varying cognitive strategies between sessions may arise from elimination of acoustic scanner noise.

Linking Pain Sensation to the Autonomic Nervous System: The Role of the Anterior Cingulate and Periaqueductal Gray Resting-State Networks.

There are bi-directional interactions between the autonomic nervous system (ANS) and pain. This is likely underpinned by a substantial overlap between brain areas of the central autonomic network and areas involved in pain processing and modulation. To date, however, relatively little is known about the neuronal substrates of the ANS-pain association. Here, we acquired resting state fMRI scans in 21 healthy subjects at rest and during tonic noxious cold stimulation. As indicators of autonomic function, we examined how heart rate variability (HRV) frequency measures were influenced by tonic noxious stimulation and how these variables related to participants' pain perception and to brain functional connectivity in regions known to play a role in both ANS regulation and pain perception, namely the right dorsal anterior cingulate cortex (dACC) and periaqueductal gray (PAG). Our findings support a role of the cardiac ANS in brain connectivity during pain, linking functional connections of the dACC and PAG with measurements of low frequency (LF)-HRV. In particular, we identified a three-way relationship between the ANS, cortical brain networks known to underpin pain processing, and participants' subjectively reported pain experiences. LF-HRV both at rest and during pain correlated with functional connectivity between the seed regions and other cortical areas including the right dorsolateral prefrontal cortex (dlPFC), left anterior insula (AI), and the precuneus. Our findings link cardiovascular autonomic parameters to brain activity changes involved in the elaboration of nociceptive information, thus beginning to elucidate underlying brain mechanisms associated with the reciprocal relationship between autonomic and pain-related systems.

Sustained perturbation in functional connectivity induced by cold pain.

BACKGROUND: Functional connectivity (FC) perturbations have been reported in multiple chronic pain phenotypes, but the nature of reported changes varies between cohorts and may relate to the consequences of living with chronic-pain related comorbidities, such as anxiety and depression. Healthy volunteer studies provide opportunities to study the effects of tonic noxious stimulation independently of these sequelae. Connectivity changes in task negative and positive networks, for example, the default mode and salience networks (DMN/SN), respectively, have been described, but how these and other connectivity networks, for example, those governing descending pain control are affected by the presence of tonic, noxious stimulation in healthy, pain-free individuals, remains unknown. METHOD: In 20 healthy volunteers, we assessed FC prior to, during, and following tonic cold painful stimulation in the ventromedial prefrontal cortex (vmPFC), rostral anterior insula (rAI), subgenual anterior cingulate cortex (ACC) and periaqueductal grey (PAG). We also recorded subjectively reported pain using a computerised visual analogue scale. RESULTS: We saw DMN FC changes during painful stimulation and that inter-network connectivity between the rAI with the vmPFC increased during pain, whereas PAG-precuneus FC decreased. Pain-induced FC alterations persisted following noxious stimulation. FC changes related to the magnitude of individuals' subjectively reported pain. CONCLUSIONS: We demonstrate FC changes during and following tonic cold-pain in healthy participants. Similarities between our findings and reports of patients with chronic pain suggest that some FC changes observed in these patients may relate to the presence of an ongoing afferent nociceptive drive. SIGNIFICANCE: How pain-related resting state networks are affected by tonic cold-pain remains unknown. We investigated functional connectivity alterations during and following tonic cold pain in healthy volunteers. Cold pain perturbed the functional connectivity of the ventro-medial prefrontal cortex, anterior insula, and the periacquaductal grey area. These connectivity changes were associated with the magnitude of individuals' reported pain. We suggest that some connectivity changes described in chronic pain patients may be due to an ongoing afferent peripheral drive.