Neuroimaging of Reward Group (NRG)
In our lab we are interested in how the reward system in the human brain is compromised in psychiatric disorders. We have developed a human experimental medicine model that utilizes chocolate to activate the reward system in the human brain. Using functional magnetic resonance imaging (fMRI) of the brain we can then examine this system under pharmacological challenges and in those "at risk" of psychiatric disorders. Understanding how these systems function will provide us with clearer targets for drug development and psychological interventions.
Depression Symptoms in Adolescents and Brains response to Reward
Rzepa, E., Fisk, J. and McCabe, C. (2017) doi: 10.1177/0269881116681416
Cannabinoids and Reward:
Recently we have begun to look at cannabinoids and opioids in relation to eating disorders. Disturbances in the regulation of reward and aversion in the brain may underlie disorders such as obesity. Tetrahydrocannabivarin (THCv) is a neutral CB1 receptor antagonist thought to have less negative side effects (depression) compared to rimonabant a CB1 inverse agonist developed as an anti-obesity treatment. In our model of reward we found rimonabant reduced reward responses but THCv increased responses in areas like the putamen. THCv also increased responses to aversive stimuli in areas like the amygdala. Our findings are the first to show that treatment with THCv might have a therapeutic activity in obesity, perhaps with a lowered risk of depressive side effects, as it doesn't reduce reward in the same way as rimonabant.
Opioids and Obesity:
Opioid antagonism reduces the consumption of palatable foods in humans but how the human brain reward system responds under antagonism is not well understood. Examining the brains response to reward and aversion in healthy people during both placebo and naltrexone treatment we found relative to placebo, naltrexone decreased reward activation to chocolate in the dorsal anterior cingulate cortex and caudate, and increased aversive-related activation to unpleasant strawberry in the amygdala and anterior insula. These findings suggest that modulation of key brain areas involved in reward processing, cognitive control and habit forming such as the dorsal anterior cingulate cortex (dACC) and caudate might underlie reduction in food intake under opioid antagonism. Furthermore we show for the first time that naltrexone can increase activations related to aversive food stimuli which might in turn be related to reduced food intake. These results support further investigation of opioid treatments in obesity.
McCabe et al., 2012, Biological Psychiatry
One of the main symptoms of depression is anhedonia, the inability to experience reward and pleasure. We have shown that those at high risk of depression such as recovered depressed individuals and also young people with a family history of depression have decreased neural responses to primary reward such as chocolate taste at the neural level. We have also found that these "at risk" groups have enhanced brain processing of unpleasant taste stimuli consistent with the literature on enhanced negative information processing in MDD. These results support our model as a viable human experimental biomarker model of reward dysfunction in MDD.
Cowdrey et al., 2011, Biological Psychiatry
We are also examining the effects eating disorders have on the brains reward system and have thus far shown that patients recovered from anorexia nervosa have increased neural response to rewarding and aversive food stimuli compared with healthy controls. Our results show clearly that recovered patients demonstrate abnormalities in the neural representation of primary and secondary food stimuli, thus supporting the suggestion that aberrant reward processes might be a biomarker of anorexia nervosa. As very little is currently known about the neural reward system in relation to anorexia nervosa these findings have important implications not only for the identification of trait markers for anorexia nervosa but also for the development of new treatments that are better equipped to address the problem of increased reactivity to food stimuli in eating disorders.
Antidepressant Treatment Effects:
McCabe et al., 2010, Biological Psychiatry
We are also interested in the effects of commonly used pharmacological treatments such as antidepressants and antipsychotics on the brains response to reward and aversion. Using our chocolate model we have shown that the widely used selective serotonin reuptake inhibitor (SSRI) antidepressant citalopram can reduce the processing of aversive stimuli, consistent with its ability to reduce negative emotional experiences. Yet we also found reduced reward processing after citalopram. These results suggest that the negative side effects of SSRIs, reported by patients, such as emotional blunting and apathy might be explained by a suppression of the reward system in the human brain.
Resting State Functional Connectivity:
Mishor and McCabe, 2011, Neuroimage
We have also been developing our interests in using neural networks of activity of the brain at rest (no task, intrinsic neural activation) to identify brain-based biomarker models for psychiatric disorders. Examining the resting state functional connectivity (RSFC) of brain regions at rest we have shown that antidepressant medications can reduce connectivity between key areas of the brain such as the amygdala and orbitofrontal cortex and striatum in healthy people. These are areas of the brain that have been found to have enhanced connectivity in those with MDD.
RSFC and Anorexia Nervosa:
Cowdrey et al. 2012, Human Brain Mapping
We have also recently examined the resting state functional connectivity (RSFC) in those recovered from anorexia nervosa and found enhanced connectivity between regions of the default mode network, salience and cognitive control networks. This is interesting given that self-focused rumination and cognitive inflexibility are thought to possibly maintain anorexa nervosa. This is the first study to investigate resting state functional connectivity in participants recovered from anorexia nervosa. These findings support the view that neural network dysfunction underlying attributes such as salience attribution and cognitive control might be a vulnerability marker for the development of anorexia nervosa.