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Systems Neuroscience of Psychopathology Lab

Harvard University Psychology Department

 

Welcome to the SNP Lab

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The Neuroscience of
Self Control

 

Why can't some people stop themselves from doing things that are bad for them? Why can't some people stop themselves from doing things that hurt others? These questions have puzzled philosophers, economists, and psychologists for centuries. The truth is that we still don't know much about why some people are really good at flexibly adapting their behavior, forgoing short term rewards to maximize long term gains, while others appear to be so bad at it. This nagging question motivates our interest in understanding the factors that shape individual differences in self-control.

Specific Research Interests

  • Neural circuit mechanisms for individual differences in impulsivity and aggression
  • Aberrant value-based decision-making in Antisocial Behavior, Psychopathy, and Substance Abuse
  • Interactions between attention, working memory, and reward in self-control
  • Implications of deficient self-control for cooperative social behavior
  • Genetic and environmental regulation of human mesolimbic dopamine circuitry

General Research Interests

  • The Cognitive Architecture of Self-Control
  • Neural bases of Individual Differences in Self-Control and in Risk for Impuse Control Disorders
  • Pathophysiology of Antisocial Behavior, Psychopathy, and Substance Abuse
  • Genetic and Epigenetic Modulation of Neural Circuitry for Emotion, Motivation, and Decision-Making
  • Cognitive and Neural Foundations for Social Norm-Based Cooperative Behavior
  • Uses (and Abuses) of Neuroscientific Data in the Courts
 

Research Summary

People vary widely in their capacity to deliberate on the potential adverse consequences of their choices before they act. Impulsivity (the inability to exert self-control) is a core symptom that contributes to dysfunction and impairment across the entire spectrum of mental illness. It is a cardinal feature of antisocial behavior, psychopathy and substance abuse, which together account for more than $1 Trillion annually in costs related to treatment, incarceration, and lost productivity. Unfortunately, impulsive symptoms are notoriously difficult to treat and there exist few effective therapeutic options.One major roadblock to treatment development is our limited understanding of the neurobiology of impulsive decision-making.

Our work is focused on identifying brain circuits that are involved in self-control in order to understand the systems-level neurobiological mechanisms that lead to individual variability in impulsivity. Our primary tools in this endeavor are brain imaging techniques - in particular,  molecular imaging with PET and MRI-based functional, structural, and connectivity imaging - which we combine with personality and behavioral assessment. Additionally, we use brain stimulation approaches such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) to manipulate nodes within distributed brain circuits for self-control; the effects of these manipulations on the larger-scale circuits are read out using PET and fMRI.  

 

 

The People

... who make the research possible

 

JoshUA Buckholtz, PhD. Lab Director

Joshua Buckholtz is an experimental psychologist and neuroscientist who uses behavioral, genetic, brain imaging, and brain stimulation methods to understand why humans vary so dramatically in their capacity for self-control. His work is focused on characterizing the cognitive architecture of self-control, identifying distinct brain circuits supporting different kinds of self-control, and understanding how dysfunction in these circuits leads to impulsive decision-making in drug addiction, aggression, psychopathy, and personality disorders. Dr. Buckholtz is a Network Scholar for the MacArthur Foundation’s Research Network on Law and Neuroscience and serves on the faculty of the Center for Law, Brain and Behavior at Massachusetts General Hospital. His is grateful for research support from the National Institute on Drug Abuse, the Alfred P. Sloan Foundation, the Brain and Behavior Research Foundation, and the MGH-CLBB.

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Lynde Folsom, Lab Manager

BA Syracuse University in Philosophy and Neuroscience
3 years at Mass General Hospital in the Neurology department working with Drs Sydney Cash, MD,PhD and Eyal Kimchi MD, PhD developing novel intracranial neural devices. When not in lab, she's hiking the White Mountains. CV

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Franchesca Ramirez, Graduate Student

Franchesca is co-mentored by Drs. Joshua Buckholtz and Matthew Nock. She studies maladaptive human responses to trauma with a focus on aggression and self-harm. Franckie integrates measures of affective and cognitive control to gain insight into how an individual’s emotion profile and decision-making process may relate behavioral outcomes to traumatic experiences.

 

Collaborators & Friends

Publications

2018

Millner AJ, Lee MD, Hoyt K, Buckholtz JW, Auerbach RP, et al. Are suicide attempters more impulsive than suicide ideators?. Gen Hosp Psychiatry. 2018

Tielbeek JJ, Al-Itejawi Z, Zijlmans J, Polderman TJ, Buckholtz JW, et al. The impact of chronic stress during adolescence on the development of aggressive behavior: A systematic review on the role of the dopaminergic system in rodents. Neurosci Biobehav Rev. 2018

Poldrack RA, Monahan J, Imrey PB, Reyna V, Raichle ME, et al. Predicting Violent Behavior: What Can Neuroscience Add?. Trends Cogn Sci. 2018


2017

Hosking JG, Kastman EK, Dorfman HM, Samanez-Larkin GR, Baskin-Sommers A, et al. Disrupted Prefrontal Regulation of Striatal Subjective Value Signals in Psychopathy. Neuron. 2017

Buckholtz JW, Karmarkar U, Ye S, Brennan GM, Baskin-Sommers A. Blunted Ambiguity Aversion During Cost-Benefit Decisions in Antisocial Individuals. Sci Rep. 2017

Smith CT, Dang LC, Buckholtz JW, Tetreault AM, Cowan RL, et al. The impact of common dopamine D2 receptor gene polymorphisms on D2/3 receptor availability: C957T as a key determinant in putamen and ventral striatum. Transl Psychiatry. 2017


2016

Baskin-Sommers A, Stuppy-Sullivan AM, Buckholtz JW. Psychopathic individuals exhibit but do not avoid regret during counterfactual decision making. Proc Natl Acad Sci U S A. 2016

Rodman AM, Kastman E, Dorfman HM, Baskin-Sommers A, Kiehl KA, et al. Selective Mapping of Psychopathy and Externalizing to Dissociable Circuits for Inhibitory Self-Control. Clin Psychol Sci. 2016


2015

Buckholtz JW, Martin JW, Treadway MT, Jan K, Zald DH, et al. From Blame to Punishment: Disrupting Prefrontal Cortex Activity Reveals Norm Enforcement Mechanisms. Neuron. 2015 Sep 23;87(6):1369-1380.

Dorfman HM, Buckholtz JW. Social Behavior: A Penny for Your Shocks. Curr Biol. 2015 Jul


2014

Dorfman HM, Meyer-Lindenberg A, Buckholtz JW. Neurobiological Mechanisms for Impulsive-Aggression: The Role of MAOA. Curr Top Behav Neurosci. 2014.

Buckholtz JW, Faigman DL. Promises, promises for neuroscience and law. Curr Biol. 2014 Sep 22;24(18):R861-R867. PubMed PMID: 25247363.

Treadway MT, Buckholtz JW, Martin JW, Jan K, Asplund CL, et al. Corticolimbic gating of emotion-driven punishment. Nat Neurosci. 2014 Sep;17(9):1270-5. PubMed PMID: 25086609.


2013

Samanez-Larkin GR, Buckholtz JW, Cowan RL, Woodward ND, Li R, Ansari M, Arrington CM, Baldwin RM, Smith CE, Treadway MT, et al. A thalamocorticostriatal dopamine network for psychostimulant-enhanced human cognitive flexibility. Biological psychiatry. 2013;74 :99–105.

Treadway MT, Buckholtz JW, Zald DH. Perceived stress predicts altered reward and loss feedback processing in medial prefrontal cortex. Front Hum Neurosci. 2013;7 :180.


2012

Treadway MT, Buckholtz JW, Cowan RL, Woodward ND, Li R, Ansari SM, Baldwin RM, Schwartzman AN, Kessler RM, Zald DH. Dopaminergic mechanisms of individual differences in human effort-based decision-making. J Neurosci. 2012;32 (18) :6170-6.

Buckholtz JW, Meyer-Lindenberg A. Psychopathology and the human connectome: toward a transdiagnostic model of risk for mental illness. Neuron. 2012;74 (6) :990-1004.

Buckholtz JW, Marois RE. The roots of modern justice: cognitive and neural foundations of social norms and their enforcement. Nature Neuroscience. 2012;15 :655–661.


2011

Treadway MT, Buckholtz JW. On the use and misuse of genomic and neuroimaging science in forensic psychiatry: current roles and future directions. Child and Adolescent Psychiatry Clinics of NA. 2011;20 :533–546


2010

Buckholtz JW, Treadway MT, Cowan RL, Woodward ND, Li R, Ansari SM, Baldwin RM, Schwartzman AN, Shelby ES, Smith CE, et al. Dopaminergic network differences in human impulsivity. Science. 2010;329 :532.

Buckholtz JW, Treadway MT, Cowan RL, Woodward ND, Benning SD, Li R, Ansari SM, Baldwin RM, Schwartzman AN, Shelby ES, et al. Mesolimbic dopamine reward system hypersensitivity in individuals with psychopathic traits. Nature Neuroscience. 2010;13 :419–421.

Blackford JU, Buckholtz JW, Avery SN, Zald DH. A unique role for the human amygdala in novelty detection. NeuroImage. 2010;50 :1188–1193.


2009

Treadway MT, Buckholtz JW, Schwartzman AN, Lambert WE, Zald DH. Worth the 'EEfRT'? The effort expenditure for rewards task as an objective measure of motivation and anhedonia. PLoS ONE. 2009;4 :e6598.


2008

Buckholtz JW, Meyer-Lindenberg A. {MAOA and the neurogenetic architecture of human aggression.}. Trends in neurosciences. 2008;31 :120–129.

Montag C, Buckholtz JW, Hartmann P, Merz M, Burk C, Hennig J, Reuter M. {COMT genetic variation affects fear processing: psychophysiological evidence.}. Behavioral neuroscience. 2008;122 :901–909.

Buckholtz JW, Asplund CL, Dux PE, Zald DH, Gore JC, Jones OD, Marois RE. {The neural correlates of third-party punishment.}. Neuron. 2008;60 :930–940.

Buckholtz JW, Callicott JH, Kolachana B, Hariri AR, Goldberg TE, Genderson M, Egan MF, Mattay VS, Weinberger DR, Meyer-Lindenberg A. Genetic variation in MAOA modulates ventromedial prefrontal circuitry mediating individual differences in human personality.Molecular Psychiatry. 2008;13 :313–324.


2007

Buckholtz JW, Meyer-Lindenberg A, Honea RA, Straub RE, Pezawas L, Egan MF, Vakkalanka R, Kolachana B, Verchinski BA, Sust S, et al. {Allelic variation in RGS4 impacts functional and structural connectivity in the human brain.}. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2007;27 :1584–1593.

Tan H-Y, Chen Q, Sust S, Buckholtz JW, Meyers JD, Egan MF, Mattay VS, Meyer-Lindenberg A, Weinberger DR, Callicott JH. {Epistasis between catechol-O-methyltransferase and type II metabotropic glutamate receptor 3 genes on working memory brain function.}. Proceedings of the National Academy of Sciences of the United States of America. 2007;104 :12536–12541.

Buckholtz JW, Sust S, Tan HY, Mattay VS, Straub RE, Meyer-Lindenberg A, Weinberger DR, Callicott JH. {fMRI evidence for functional epistasis between COMT and RGS4.}. Molecular Psychiatry. 2007;12 :893–5– 885.


2006

Meyer-Lindenberg A, Buckholtz JW, Kolachana B, R Hariri A, Pezawas L, Blasi G, Wabnitz A, Honea R, Verchinski B, Callicott JH, et al. {Neural mechanisms of genetic risk for impulsivity and violence in humans.}. Proceedings of the National Academy of Sciences of the United States of America. 2006;103 :6269–6274.Abstract

Tan H-Y, Sust S, Buckholtz JW, Mattay VS, Meyer-Lindenberg A, Egan MF, Weinberger DR, Callicott JH. {Dysfunctional prefrontal regional specialization and compensation in schizophrenia.}. The American journal of psychiatry. 2006;163 :1969–1977.


1996

Classes


Bad Genes, Bad Parents, Bad Behaviors

This class will explore the biology of criminal behavior and violence. We will examine the construct of "anti-sociality" and unpack clinical and diagnostic issues surrounding its diverse manifestations, such as psychopathy. A strong emphasis will be placed on biological mechanisms. A particular focus will be on understanding how genes and environments act and interact to predispose antisocial behavior by shaping brain function and development.


Mind, Brain, Illness

This course is focused on understanding the causal mechanisms of mental illness. We examine the concept of mental illness and the relationship between psychopathological symptoms and specific brain circuits for executive control, motivation, social cognition, and emotion regulation. Further, we explore the ways in which genetic and environmental factors affect the function of these circuits to predispose psychological dysfunction.


Circuits and Symptoms

 

This class will explore the biology of psychological illness. We will ignore artificial diagnostic labels, examining instead the core symptom domains that have plagued humans since the beginning of recorded history. A strong emphasis will be placed on biological mechanisms. In particular, the class will focus on mapping dysfunction in large-scale brain circuits to cognitive, affective, social, and motivational symptom domains, and on understanding how genes and environments act and interact to predispose these symptoms by shaping brain function and development.


Introduction to the study of psychological dysfunction. Focuses on abnormal behavior as it relates to the definition, etiology, and treatment of major forms of psychopathology, including depression, anxiety, phobias, PTSD, OCD, addiction, autism, schizophrenia, and psychopathy. This course will emphasize critical evaluation of the causes and mechanisms of mental disorders, with special attention paid to recent neuroscientific and genetic research on the neurobiology of psychopathology.


Circuits and Symptoms

 

This class will explore the biology of psychological illness. We will ignore artificial diagnostic labels, examining instead the core symptom domains that have plagued humans since the beginning of recorded history. A strong emphasis will be placed on biological mechanisms. In particular, the class will focus on mapping dysfunction in large-scale brain circuits to cognitive, affective, social, and motivational symptom domains, and on understanding how genes and environments act and interact to predispose these symptoms by shaping brain function and development.

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Join Us

NorthWest Building, 295
52 Oxford St
Cambridge MA 02138-1903

 
 

Contact Us

If you are interested in joining the lab, collaborating, or participating in a study, please feel free to reach out with this form!

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