Introduction

The main goal of the research in the Affective Neuroscience Laboratory is to investigate the brain mechanisms underlying affective processing in normal individuals and participants with mood disorders, particularly major depression. Under the direction of Prof. Diego Pizzagalli, the lab utilizes various functional neuroimaging techniques (electroencephalography, EEG; functional magnetic resonance imaging, fMRI; and positron emission tomography, PET) to investigate (a) the functional neuroanatomy of depression, (b) the brain substrates of individual differences in affective style and vulnerability to affective disorders, and (c) the brain mechanisms of affective processing and cognition-emotion interactions.

In recent years, we have devoted our efforts to parsing the heterogeneity of depression. Our research has shown that there are specific patterns of brain activation that correspond to individual differences in treatment response, depression severity, anxiety symptoms, and phenotypes of depression. Currently we are developing new approaches for predicting treatment response in major depression by integrating information gathered from three levels of analysis: (1) behavior, (2) brain function, and (3) genes.

Another goal of the laboratory is to investigate the neurobiological underpinnings of anhedonia (loss of pleasure), which is an important trait marker of vulnerability to psychopathology. To this end, we have developed new objective approaches to measure subjects’ ability to modulate behavior as a function of their prior exposure to reward. In particular, we have developed a probabilistic reward task based on a differential reinforcement schedule that allows us to objectively assess participants' propensity to modulate behavior as a function of reward history. We are currently investigating the effects of genetic vulnerability and stress on these hedonic responses. For a summary of our findings using the probabilistic reward task, click here.

Additional ongoing studies in our laboratory investigate brain mechanisms underlying emotional regulation and emotion-cognition interaction (e.g., how does emotionally laden feedback about one’s performance modulate one’s decision making). For these studies, our participants include healthy control subjects, clinically depressed subjects, and at-risk subjects (e.g., remitted depressed subjects).

Our laboratory has ongoing collaborations with the MGH Psychiatric Neuroimaging Research Group, the MGH Depression Clinical and Research Program, the MGH Psychiatric and Neurodevelopmental Genetics Unit, and the Center for Anxiety and Related Disorders at Boston University. Our research is supported by the National Institute of Mental Health (NIMH), the National Center for Complementary and Alternative Medicine (NCCAM), various private foundations, and the pharmaceutical industry.

Pizzagalli, D.A., Jahn, A.L., O'Shea, J.P. (2005). Toward an objective characterization of an anhedonic phenotype: A Signal-detection approach. Biological Psychiatry, 57, 319-327.

Pizzagalli DA, Oakes TR, Davidson RJ (2003). Coupling of theta activity and glucose metabolism in the human rostral anterior cingulate cortex: An EEG/PET study of normal and depressed subjects. Psychophysiology, 40, 939-949.

Pizzagalli, D.A., Oakes, T.R., Fox, A.S., Chung, M.K., Larson, C.L., Abercrombie, H.C., Schaefer, S.M., Benca, R.M., Davidson, R.J. (2004). Functional but not structural subgenual prefrontal cortex abnormalities in melancholia. Molecular Psychiatry, 9, 393-405.

Pizzagalli, D.A., Nitschke, J.B., Oakes, T.R., Hendrick, A.M., Horras, K.A., Larson, C.L., Abercrombie, H.C., Schaefer, S.M., Koger, J.V., Benca, R.M., Pascual-Marqui, R.D., Davidson, R.J. (2002). Brain electrical tomography in depression: The importance of symptom severity, anxiety, and melancholic features. Biological Psychiatry, 52, 73-85.

Pizzagalli, D., Pascual-Marqui, R.D., Nitschke, J.B., Oakes, T.R., Larson, C.L., Abercrombie, H.C., Schaefer, S.M., Koger, J.V., Benca, R.M., Davidson, R.J. (2001). Anterior cingulate activity as a predictor of degree of treatment response in major depression: Evidence from brain electrical tomography analysis. American Journal of Psychiatry, 158, 405-415.

Pizzagalli, D.A., Peccoralo, L.A., Davidson, R.J., Cohen, J.D. (2006). Resting anterior cingulate activity and abnormal responses to errors in subjects with elevated depressive symptoms: A 128-channel EEG study. Human Brain Mapping, 27, 185-201.

Spatio-temporal dynamics of brain mechanisms underlying affective processing

Chiu, P.H., Holmes, A.J., Pizzagalli, D.A. (in press). Dissociable recruitment of rostral anterior cingulate and inferior frontal cortex in emotional response inhibition. NeuroImage, doi:10.1016/j.neuroimage.2008.04.248

Dillon, D.G., Holmes, A.J., Jahn, A.L., Bogdan, R., Wald, L.L., Pizzagalli, D.A. (2008). Dissociation of neural regions associated with anticipatory versus consummatory phases of incentive processing. Psychophysiology 45, 36-49.

Pizzagalli, D.A., Evins, A.E., Schetter Cowman, E., Frank, M.J., Pajtas, P.E., Santesso, D.L., Culhane, M. (2008). Single dose of a dopamine agonist impairs reinforcement learning in humans: Behavioral evidence from a laboratory-based measure of reward responsiveness. Psychopharmacology, 196, 221-232.

Pizzagalli, D.A., Lehmann, D., Hendrick, A.M., Regard, M., Pascual-Marqui, R.D., Davidson, R.J. (2002). Affective judgments of faces modulate early activity (~160 ms) within the fusiform gyri. NeuroImage, 16, 663-677.

Pizzagalli, D., Shackman, A.J., & Davidson, R.J. (2002). The functional neuroimaging of human emotion: Asymmetric contributions of cortical and subcortical circuitry. In: K. Hughdal, R.J. Davidson (Eds.), The Asymmetrical Brain. Cambridge: MIT Press, pp. 511-532.

Pizzagalli, D.A., Sherwood, R.J., Henriques, J.B., Davidson, R.J. (2005). Frontal brain asymmetry and reward responsiveness: A Source localization study. Psychological Science, 16, 805-813

Santesso, D.L., Dillon, D.G., Birk, J.L, Holmes, A.J., Goetz, E., Bogdan, R., Pizzagalli, D.A. (2008). Individual differences in reinforcement learning: Behavioral, electrophysiological, and neuroimaging correlates. NeuroImage, doi:10.1016/j.neuroimage.2008.05.032.

Santesso, D.L., Evins, A.E., Frank, M.J., Schetter Cowman, E., Pizzagalli, D.A. (in press). Single dose of a dopamine agonist impairs reinforcement learning in humans: Evidence from electrophysiology and computational modeling of striatal-cortical function. Human Brain Mapping.

The research conducted in this lab is supported by NIMH Research Grant R01MH68376 and the Talley Fund.