The Neural Mechanisms Behind Effective Psychotherapy

A brain-based perspective could explain how and why psychotherapy leads to enduring change.

For several years my colleagues and I have pursued a simple question with profound implications for psychiatric practice: how does psychotherapy work? We want to capitalize on major advances in our understanding of the neural basis of memory, emotion, and emotion-memory interactions. If we could start to explain the basic mechanism of action behind psychotherapy, then maybe we could understand how to conduct psychotherapy more effectively, with the ultimate goal of working with our patients to produce lasting changes in their mental health.

The New Neuroscience of Memory

Recent studies have made important discoveries about the neural mechanisms underlying memory. Four are of particular interest. First, memories are not fixed entities; rather, they enter a labile state whenever they are reactivated, and can be modified or updated with new information during a 4 to 6 hour window after reactivation.1 Second, specific episodic (event) memories and semantic (generalizable knowledge) memories are highly inter-related in that they share neural mechanisms, and the latter are a distillation of the former.2 Third, memories that are emotionally charged are remembered better than those that are not.3 And fourth, the activation of emotion appears to be a necessary ingredient of successful outcomes in psychotherapy.4,5

Drawing upon these observations, my colleagues and I hypothesized that there were 3 key ingredients to lasting change in psychotherapy: 1) activating problematic memories and the associated painful affect; 2) concurrently engaging new emotional experiences that change old memories through reconsolidation; 3) reinforcing the strength of new memories and their semantic structures by practicing new ways of behaving and experiencing the world in a variety of contexts. In a 2015 article in a leading neuroscience journal,4 we briefly discussed the application of this model to 4 different psychotherapy modalities, including behavioral, cognitive behavioral (CBT), emotion focused (EFT), and psychodynamic psychotherapies..

Diving Into the Research—and the Clinical Implications

Realizing that there was much more to say about this new way of understanding change in psychotherapy, my colleagues and I published an edited volume, with multiple contributors, that both explains the basic science of memory and outlines a clinical application of our model. The new book, Neuroscience of Enduring Change: Implications for Psychotherapy, expands upon the previous work in 3 sections.6 The basic science section includes chapters on emotion, memory, emotion-memory interactions, the role of language in shaping emotion and memory, and the role of sleep in memory consolidation and reconsolidation. The clinical section includes chapters from leading experts in psychodynamic psychotherapy, CBT, EFT, coherence therapy, and integrative approaches. Each author considers the role of memory reconsolidation in both psychotherapy and in achieving lasting personal change. The final section includes chapters on recurrent maladaptive patterns, a computational neuroscience perspective on the proposed model, and a discussion of a proposed preclinical and clinical research agenda.

Considerable effort was made within and across chapters to promote cross-fertilization between basic science and clinical application. Although it is written for neuroscience-oriented mental health clinicians, all psychotherapists, psychotherapy researchers, and scientists interested in memory, emotion, and their clinical application will find new ideas and practical advice in this book. An independent book review has been published.7

If one takes this model seriously it could influence psychiatric practice in several ways. For example, it is useful to consider how interventions might be adjusted in therapies that have stalled or have failed. Rather than talking about feelings with the goal of promoting insight, it is also important to experience feelings, especially the old painful feelings from which individuals have protected themselves for years, and to juxtapose these feelings with corrective emotional experiences.

Another clinical implication emerges from the observation that consolidation of emotional memories occurs primarily during REM sleep. Because reconsolidation may work in the same way, medications that inhibit REM sleep may be counterproductive to enduring change in psychotherapy. It is therefore important to know that selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitor, tricyclics, and benzodiazepines inhibit REM sleep, whereas trazodone, buproprion, and mirtazapine do not.8,9. The book describes these and other implications and provides a fresh perspective on how psychotherapy practice may be optimized and integrated in psychiatric care.

The Story Behind the Book

My interest in this topic emerged over the course of my 35-year career as an academic psychiatrist. I was initially trained as a clinical psychiatrist and psychodynamic psychotherapist and have continued to practice and supervise residents ever since. I was also fortunate enough to receive research training (resulting in a PhD in experimental psychology) that focused on cognitive neuroscience and functional neuroimaging of emotion. I have found the dialogue between the basic science of psychiatry and its clinical application to be particularly enriching and informative.

In my role as educator, I have become well acquainted with the challenges (eg, significant differences in the theoretical backgrounds, mindset, and clinical interventions required by these different approaches) psychiatry residents face in developing competence in CBT, psychodynamic psychotherapy, and supportive psychotherapy. Because there is a strong interest in finding common factors and common mechanisms across psychotherapy modalities, it occurred to me that a systems neuroscience perspective could provide an integrative mechanistic framework that would highlight commonalities instead of divergences. Moreover, the goal of integrating pharmacotherapy and psychotherapy is likely to be advanced by explaining how each works in brain-based terms. In my efforts to develop a new brain-based model of change in psychotherapy, I have been fortunate to have remarkable collaborators, including Lynn Nadel, PhD, Emeritus Professor of Psychology at the University of Arizona (a pioneer in the newly emerging understanding of memory).

Concluding Thoughts

It is important to emphasize that we have not yet established that change in psychotherapy occurs through memory reconsolidation. One of the conclusions of our book is that a focus of intervention is recurrent maladaptive patterns, which can be understood as an expression of schemas. Schematic memory is a type of semantic memory and, as an area of neuroscientific investigation, it is relatively new. It remains to be demonstrated empirically that schematic memories can be updated with emotional information. If so, it must then be determined whether this applies to psychotherapy. Although research of this type is still underway, it might be argued that it is important to consider the clinical implications of this model if it were true.

Dr Lane is professor of psychiatry, psychology, and neuroscience at the University of Arizona.


1. Phelps EA, Hofmann SG. Memory editing from science fiction to clinical practice. Nature. 2019;572(7767):43-50.

2. Ryan L, Hoscheidt S, Nadel L. Perspectives on episodic and semantic memory retrieval. In: Dere A, Easton J, Huston J, Nadel L, eds. Handbook of Episodic Memory. Elsevier; 2008:5-18.

3. Kalbe F, Schwabe L. Beyond arousal: Prediction error related to aversive events promotes episodic memory formation. J Exp Psychol Learn Mem Cogn. 2020;46(2):234-246.

4. Lane RD, Ryan L, Nadel L, Greenberg L. Memory reconsolidation, emotional arousal, and the process of change in psychotherapy: New insights from brain science. Behav Brain Sci. 2015;38:e1.

5. Auszra L, Greenberg LS, Herrmann I. Client emotional productivity-optimal client in-session emotional processing in experiential therapy. Psychother Res. 2013;23(6):732-746.

6. Lane RD, Nadel L, eds. Neuroscience of Enduring Change: Implications for Psychotherapy. Oxford University Press; 2020.

7. Kramer U. Review of “Neuroscience of Enduring Change: Implications for Psychotherapy.” Am J Psychother. 2021;74:44-45.

8. Doghramji K, Jangro WC. Adverse effects of psychotropic medications on sleep. Psychiatr Clin North Am. 2016;39(3):487-502. 

9. Borbély AA, Mattmann P, Loepfe M, Strauch I, Lehmann D. Effect of benzodiazepine hypnotics on all-night sleep EEG spectra. Hum Neurobiol. 1985;4(3):189-194.