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Joseph E. LeDoux
Joseph E. LeDoux (born December 7, 1949) is an American neuroscientist whose research is primarily focused on the biological underpinnings of emotion and memory, especially brain mechanisms related to fear and anxiety. LeDoux is the Henry and Lucy Moses Professor of Science at New York University, and director of the Emotional Brain Institute, a collaboration between NYU and New York State with research sites at NYU and the Nathan Kline Institute for Psychiatric Research in Orangeburg, New York. He is also the lead singer and songwriter in the band The Amygdaloids.
== Research and theories ==
As explained in his 1996 book, The Emotional Brain,〔LeDoux JE (1996) The Emotional Brain. New York: Simon and Schuster.〕 LeDoux developed an interest in the topic of emotion through his doctoral work with Michael Gazzaniga on split-brain patients in the mid-1970s.〔Gazzaniga MS, LeDoux JE (1978) The Integrated Mind. New York: Plenum.〕 Because techniques for studying the human brain were limited at the time, he turned to studies of rodents where the brain could be studied in detail. He chose to focus on a simple behavioral model, Pavlovian fear conditioning. This procedure allowed him to follow the flow of information about a stimulus through the brain as it comes to control behavioral responses by way of sensory pathways to the amygdala, and gave rise to the notion of two sensory roads to the amygdala, with the “low road” being a quick and dirty subcortical pathway for rapidly activity behavioral responses to threats and the “high road” providing slower but highly processed cortical information.〔LeDoux JE (1994) Emotion, memory and the brain. Sci Am 270:50-57.〕 His work has shed light on how the brain detects and responds to threats, and how memories about such experiences are formed and stored through cellular, synaptic and molecular changes in the amygdala.〔LeDoux JE (2002) Synaptic Self: How our brains become who we are. New York: Viking; LeDoux JE (2000) Emotion circuits in the brain. Annu Rev Neurosci 23:155-184; Rodrigues SM, Schafe GE, LeDoux JE (2004) Molecular mechanisms underlying emotional learning and memory in the lateral amygdala. Neuron 44:75-91; Johansen JP, Cain CK, Ostroff LE, LeDoux JE (2011) Molecular mechanisms of fear learning and memory. Cell 147:509-524.〕 A long-standing collaboration with NYU colleague Elizabeth Phelps has shown the validity of the rodent work for understanding threat processing in the human brain.〔Phelps EA, LeDoux JE (2005) Contributions of the amygdala to emotion processing: from animal models to human behavior. Neuron 48:175-187; Phelps EA (2006) Emotion and cognition: insights from studies of the human amygdala. Annu Rev Psychol 57:27-53.〕
LeDoux’s work on amygdala processing of threats has helped understand exaggerated responses to threats in anxiety disorders in humans.〔LeDoux JE (2002) Synaptic Self: How our brains become who we are. New York: Viking; LeDoux JE (2015) Anxious: Using the Brain to Understand and Treat Fear and Anxiety. New York: Viking.〕 For example, studies with Maria Morgan in the 1990s implicated the medial prefrontal cortex in the extinction of responses to threats〔Morgan MA, Romanski LM, LeDoux JE (1993) Extinction of emotional learning: contribution of medial prefrontal cortex. Neurosci Lett 163:109-113; Morgan MA, LeDoux JE (1995) Differential contribution of dorsal and ventral medial prefrontal cortex to the acquisition and extinction of conditioned fear in rats. Behav Neurosci 109:681-688; Sotres-Bayon F, Bush DE, LeDoux JE (2004) Emotional perseveration: an update on prefrontal-amygdala interactions in fear extinction. Learn Mem 11:525-535.〕 and paved the way for understanding how exposure therapy reduces threat reactions in people with anxiety by way of interactions between the medial prefrontal cortex and the amygdala.〔LeDoux JE (1996) The Emotional Brain. New York: Simon and Schuster; LeDoux JE (2002) Synaptic Self: How our brains become who we are. New York: Viking; LeDoux JE (2015) Anxious: Using the Brain to Understand and Treat Fear and Anxiety. New York: Viking; Shin, L.M., S.L. Rauch, R.K. Pitman. “Amygdala, Medial Prefrontal Cortex, and Hippocampal Function in PTSD.” Annals of the New York Academy of Sciences (2006) 1071:67–79; Mathew, S.J., R.B. Price, and D.S. Charney. “Recent Advances in the Neurobiology of Anxiety Disorders: Implications for Novel Therapeutics.” American Journal of Medical Genetics Part C, Seminars in Medical Genetics (2008) 148C:89–98.〕 Work conducted with Karim Nader and Glenn Schafe triggered a wave of interest in the topic of memory reconsolidation, Nader K, Schafe GE, LeDoux JE (2000) Fear memories require protein synthesis in the amygdala for reconsolidation after retrieval. Nature 406:722-726 a process by which memories become labile and subject to change after being retrieved.〔Nader K and Einarsson EO (2010) Memory Reconsolidation: An Update. Ann NY Acad Sci 1191:27-41; Dudai Y and Eisenberg M (2004) Rights of passage of the engram: Reconsolidation and the lingering consolidation hypothesis. Neuron 44:93-100; Tronson NC and Taylor JR (2007) Molecular mechanisms of memory reconsolidation. Nat Rev Neurosci 8:262-275; Alberini CM (ed.) (2013) Memory Reconsolidation. New York: Elsevier.〕 This led to the idea that that trauma-related cues might weakened in humans by blocking reconsolidation. Studies with Marie Mofils, Daniela Schiller and Phelps showed that extinction conducted shortly after triggering reconsolidation is considerably more effective in reducing the threat value of stimuli than conventional extinction,〔Monfils MH, Cowansage KK, Klann E, LeDoux JE (2009) Extinction-reconsolidation boundaries: key to persistent attenuation of fear memories. Science 324:951-955; Schiller D, Monfils MH, Raio CM, Johnson DC, LeDoux JE, Phelps EA (2010) Preventing the return of fear in humans using reconsolidation update mechanisms. Nature 463:49-53; Schiller D, Kanen JW, LeDoux JE, Monfils MM, and Phelps EA (2013) Extinction during reconsolidation of thereat memory diminishes prefrontal cortex involvement. Proc Natl Acad Sci USA 110:20040-20045.〕 a finding that has proven useful in reducing drug relapse in humans.〔Xue YX, Luo YX, Wu P, Shi HS, Xue LF, Chen C, Zhu WL, Ding ZB, Bao YP, Shi J, Epstein DH, Shaham Y, Lu L (2012) A memory retrieval-extinction procedure to prevent drug craving and relapse. Science 336:241-245.〕
Recently, LeDoux has begun to emphasize the value, when discussing brain functions in animals, of using terms that are not derived from human subjective experience.〔LeDoux J (2012) Rethinking the emotional brain. Neuron 73:653-676.〕 The common practice of calling brain circuits that detect and respond to threats “fear circuits” implies that these circuits are responsible for feelings of fear. LeDoux has argued that so-called Pavlovian fear conditioning should be renamed Pavlovian threat conditioning to avoid the implication that “fear” is being acquired in rats or humans.〔LeDoux JE (2014) Coming to terms with fear. Proc Natl Acad Sci U S A 111:2871-2878.〕 Key to his theoretical change is the notion of survival functions mediated by survival circuits, the purpose of which is to keep organisms alive rather than to make emotions. For example, defensive survival circuits exist to detect and respond to threats. While all organisms can do this, only organisms that can be conscious of their own brain’s activities can feel fear. Fear is a conscious experience and occurs the same way as any other kind of conscious experience: via cortical circuits that allow attention to certain forms of brain activity. He argues the only differences between an emotional and non-emotion state of consciousness are the underlying neural ingredients that contribute to the state.〔LeDoux JE (2015) Feelings: What are they and how does the brain make them? Daedalus 144.〕 These ideas and their implications for understanding the neural foundations of pathological fear and anxiety are explained in his 2015 book, Anxious.〔LeDoux JE (2015) Anxious: Using the Brain to Understand and Treat Fear and Anxiety. New York: Viking.〕
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