Modulatory effects of dynamic fMRI-based neurofeedback on emotion regulation networks in adolescent females

Research has shown that difficulties with emotion regulation abilities in childhood and adolescence increase the risk for developing symptoms of mental disorders, e.g anxiety. We investigated whether functional magnetic resonance imaging (fMRI)-based neurofeedback (NF) can modulate brain networks supporting emotion regulation abilities in adolescent females. We performed three experiments (Experiment 1: N = 18; Experiment 2: N = 30; Experiment 3: N = 20). We first compared different NF implementations regarding their effectiveness of modulating prefrontal cortex (PFC)-amygdala functional connectivity (fc). Further we assessed the effects of fc-NF on neural measures, emotional/metacognitive measures and their associations. Finally, we probed the mechanism underlying fc-NF by examining concentrations of inhibitory and excitatory neurotransmitters. Results showed that NF implementations differentially modulate PFC-amygdala fc. Using the most effective NF implementation we observed important relationships between neural and emotional/metacognitive measures, such as practice-related change in fc was related with change in thought control ability. Further, we found that the relationship between state anxiety prior to the MRI session and the effect of fc-NF was moderated by GABA concentrations in the PFC and anterior cingulate cortex. To conclude, we were able to show that fc-NF can be used in adolescent females to shape neural and emotional/metacognitive measures underlying emotion regulation. We further show that neurotransmitter concentrations moderate fc–NF–effects.

[1]  Nikolaos Karalis,et al.  Prefrontal parvalbumin interneurons shape neuronal activity to drive fear expression , 2013, Nature.

[2]  Richard J. Davidson,et al.  Regulation--A Possible Prelude to Violence Dysfunction in the Neural Circuitry of Emotion , 2006 .

[3]  D. Mantini,et al.  Functional and neurochemical interactions within the amygdala–medial prefrontal cortex circuit and their relevance to emotional processing , 2016, Brain Structure and Function.

[4]  Sarah-Jayne Blakemore,et al.  The relationship between puberty and social emotion processing , 2012, Archives of Disease in Childhood.

[5]  A. Hayes.  Introduction to Mediation, Moderation, and Conditional Process Analysis: A Regression-Based Approach , 2013 .

[6]  T. Paus,et al.  Why do many psychiatric disorders emerge during adolescence? , 2008, Nature Reviews Neuroscience.

[7]  Jay N. Giedd,et al.  The influence of puberty on subcortical brain development , 2014, NeuroImage.

[8]  Bettina Sorger,et al.  fMRI neurofeedback facilitates anxiety regulation in females with spider phobia , 2015, Front. Behav. Neurosci..

[9]  D. Pine,et al.  Emotional Reactivity and Risk for Psychopathology Among Adolescents , 2001, CNS Spectrums.

[10]  J. Luciano,et al.  Development and validation of the thought control ability questionnaire , 2005 .

[11]  D. Weinberger,et al.  Neocortical modulation of the amygdala response to fearful stimuli , 2003, Biological Psychiatry.

[12]  M. Lee,et al.  Bayesian Cognitive Modeling: A Practical Course , 2014 .

[13]  B. Sahakian,et al.  The mental wealth of nations , 2008, Nature.

[14]  J. Reis,et al.  Pre-Trial EEG-Based Single-Trial Motor Performance Prediction to Enhance Neuroergonomics for a Hand Force Task , 2016, Front. Hum. Neurosci..

[15]  L. Pessoa,et al.  An fMRI Pilot Study of Cognitive Reappraisal in Children: Divergent Effects on Brain and Behavior , 2015, Journal of psychopathology and behavioral assessment.

[16]  Jianfeng Feng,et al.  Using real-time fMRI to influence effective connectivity in the developing emotion regulation network , 2016, NeuroImage.

[17]  V. Chefer,et al.  Basolateral Amygdala-Driven Augmentation of Medial Prefrontal Cortex GABAergic Neurotransmission in Response to Environmental Stimuli Associated with Cocaine Administration , 2011, Neuropsychopharmacology.

[18]  C. Frith.  The social brain? , 2007, Philosophical Transactions of the Royal Society B: Biological Sciences.

[19]  C. Sebastian,et al.  Developmental Cognitive Neuroscience Neurocognitive Bases of Emotion Regulation Development in Adolescence , 2022 .

[20]  P. Whalen,et al.  The structural and functional connectivity of the amygdala: From normal emotion to pathological anxiety , 2011, Behavioural Brain Research.

[21]  G. Scerif,et al.  Measuring online interpretations and attributions of social situations: Links with adolescent social anxiety. , 2016, Journal of behavior therapy and experimental psychiatry.

[22]  J. Lau,et al.  A developmental angle to understanding the mechanisms of biased cognitions in social anxiety , 2014, Front. Hum. Neurosci..

[23]  P. Renshaw,et al.  Effects of yoga versus walking on mood, anxiety, and brain GABA levels: a randomized controlled MRS study. , 2010, Journal of alternative and complementary medicine.

[24]  R. Little.  A Test of Missing Completely at Random for Multivariate Data with Missing Values , 1988 .

[25]  S. Provencher.  Estimation of metabolite concentrations from localized in vivo proton NMR spectra , 1993, Magnetic resonance in medicine.

[26]  C. Spielberger,et al.  Measuring anxiety and anger with the State-Trait Anxiety Inventory (STAI) and the State-Trait Anger Expression Inventory (STAXI). , 1999 .

[27]  Jean-Luc Anton,et al.  Region of interest analysis using an SPM toolbox , 2010 .

[28]  P. Goldman-Rakic,et al.  A role for inhibition in shaping the temporal flow of information in prefrontal cortex , 2002, Nature Neuroscience.

[29]  Jarrod A. Lewis-Peacock,et al.  Closed-loop brain training: the science of neurofeedback , 2017, Nature Reviews Neuroscience.

[30]  S. Provencher.  Automatic quantitation of localized in vivo 1H spectra with LCModel , 2001, NMR in biomedicine.

[31]  P. Lichtenstein,et al.  Benzodiazepine prescribing for children, adolescents, and young adults from 2006 through 2013: A total population register-linkage study , 2018, PLoS medicine.

[32]  D. C. Howell.  Statistical Methods for Psychology , 1987 .

[33]  N. Voets,et al.  Metabolite-cycled density-weighted concentric rings k-space trajectory (DW-CRT) enables high-resolution 1 H magnetic resonance spectroscopic imaging at 3-Tesla , 2018, Scientific Reports.

[34]  Bettina Sorger,et al.  Windowed Correlation: A Suitable Tool for Providing Dynamic fMRI-Based Functional Connectivity Neurofeedback on Task Difficulty , 2014, PloS one.

[35]  A. Wells,et al.  The Thought Control Questionnaire: a measure of individual differences in the control of unwanted thoughts. , 1994, Behaviour research and therapy.

[36]  D. Linden.  The Challenges and Promise of Neuroimaging in Psychiatry , 2012, Neuron.

[37]  Christian Paret,et al.  Current progress in real-time functional magnetic resonance-based neurofeedback: Methodological challenges and achievements , 2019, NeuroImage.

[38]  A. Meyer-Lindenberg,et al.  5-HTTLPR polymorphism impacts human cingulate-amygdala interactions: a genetic susceptibility mechanism for depression , 2005, Nature Neuroscience.

[39]  Dimitri Van De Ville,et al.  Connectivity-based neurofeedback: Dynamic causal modeling for real-time fMRI☆ , 2013, Neuroimage.

[40]  Simon B. Eickhoff,et al.  A new SPM toolbox for combining probabilistic cytoarchitectonic maps and functional imaging data , 2005, NeuroImage.

[41]  J. Gross,et al.  The cognitive control of emotion , 2005, Trends in Cognitive Sciences.

[42]  S. Blakemore.  The social brain in adolescence , 2008, Nature Reviews Neuroscience.

[43]  Dimitri Van De Ville,et al.  Meta-analysis of real-time fMRI neurofeedback studies using individual participant data: How is brain regulation mediated? , 2016, NeuroImage.

[44]  Todd A. Hare,et al.  A Developmental Shift from Positive to Negative Connectivity in Human Amygdala–Prefrontal Circuitry , 2013, The Journal of Neuroscience.

[45]  R. Davidson,et al.  Dysfunction in the neural circuitry of emotion regulation--a possible prelude to violence. , 2000, Science.

[46]  P. Nuss,et al.  Anxiety disorders and GABA neurotransmission: a disturbance of modulation , 2015, Neuropsychiatric disease and treatment.

[47]  S. W. Rieger,et al.  Learning Control Over Emotion Networks Through Connectivity‐Based Neurofeedback , 2015, Cerebral cortex.

[48]  Christian Mühl,et al.  Flaws in current human training protocols for spontaneous Brain-Computer Interfaces: lessons learned from instructional design , 2013, Front. Hum. Neurosci..

[49]  Bettina Sorger,et al.  Real-Time Self-Regulation of Emotion Networks in Patients with Depression , 2012, PloS one.

[50]  Adam W. McCrimmon,et al.  Review of the Wechsler Abbreviated Scale of Intelligence, Second Edition (WASI-II) , 2013 .

[51]  Jennifer Y F Lau,et al.  Plasticity during childhood and adolescence: innovative approaches to investigating neurocognitive development. , 2013, Developmental science.

[52]  G. Glover,et al.  Biological Substrates of Emotional Reactivity and Regulation in Adolescence During an Emotional Go-Nogo Task , 2008, Biological Psychiatry.

[53]  A. La Greca,et al.  Social Anxiety Among Adolescents: Linkages with Peer Relations and Friendships , 1998, Journal of abnormal child psychology.

[54]  Larry Ambrose,et al.  The power of feedback. , 2002, Healthcare executive.

[55]  Jerzy Bodurka,et al.  Prefrontal Control of the Amygdala during Real-Time fMRI Neurofeedback Training of Emotion Regulation , 2013, PloS one.

[56]  Jacob N Keynan,et al.  Process-based framework for precise neuromodulation , 2019, Nature Human Behaviour.

[57]  R T Constable,et al.  Orbitofrontal cortex neurofeedback produces lasting changes in contamination anxiety and resting-state connectivity , 2013, Translational Psychiatry.

[58]  Tom Johnstone,et al.  Inverse amygdala and medial prefrontal cortex responses to surprised faces , 2003, Neuroreport.

[59]  Christopher S. Monk,et al.  Age‐related changes in amygdala–frontal connectivity during emotional face processing from childhood into young adulthood , 2016, Human brain mapping.

[60]  L. M. M.-T..  Theory of Probability , 1929, Nature.

[61]  Robert L. Leahy,et al.  The Use of Psychological Testing for Treatment Planning and Outcome Assessment , 2000, Journal of Cognitive Psychotherapy.

[62]  Nikolaus Weiskopf,et al.  Cognitive enhancement through real-time fMRI neurofeedback , 2015, Current Opinion in Behavioral Sciences.

[63]  P. Renshaw,et al.  Yoga Asana sessions increase brain GABA levels: a pilot study. , 2007, Journal of alternative and complementary medicine.

[64]  W. Revelle.  psych: Procedures for Personality and Psychological Research , 2017 .

[65]  Lao Juan,et al.  Development and Validation of a Scale for Measuring Instructors' Attitudes toward Concept-Based or Reform-Oriented Teaching of Introductory Statistics in the Health and Behavioral Sciences , 2010, 1007.3219.

[66]  Gaia Scerif,et al.  Social anxiety disorder in adolescence: How developmental cognitive neuroscience findings may shape understanding and interventions for psychopathology , 2015, Developmental Cognitive Neuroscience.

[67]  Kamryn T. Eddy,et al.  Amygdala-frontal connectivity during emotion regulation. , 2007, Social cognitive and affective neuroscience.

[68]  Kathrin Cohen Kadosh,et al.  The social brain in adolescence: Evidence from functional magnetic resonance imaging and behavioural studies , 2011, Neuroscience & Biobehavioral Reviews.

[69]  C. Trentacosta,et al.  Emotion Knowledge, Social Competence, and Behavior Problems in Childhood and Adolescence: A Meta-Analytic Review. , 2010, Social development.

[70]  Reinhold Scherer,et al.  Mind the Traps! Design Guidelines for Rigorous BCI Experiments , 2018 .

[71]  D. Derryberry,et al.  Anxiety-related attentional biases and their regulation by attentional control. , 2002, Journal of abnormal psychology.

[72]  Geraint Rees,et al.  Better Ways to Improve Standards in Brain-Behavior Correlation Analysis , 2012, Front. Hum. Neurosci..

[73]  John O. Willis,et al.  Wechsler Abbreviated Scale of Intelligence , 2014 .

[74]  Angela R. Laird,et al.  Neural network of cognitive emotion regulation — An ALE meta-analysis and MACM analysis , 2014, NeuroImage.

[75]  P. Whalen,et al.  The Structural Integrity of an Amygdala–Prefrontal Pathway Predicts Trait Anxiety , 2009, The Journal of Neuroscience.

[76]  C. Frith,et al.  Recruitment of lateral rostral prefrontal cortex in spontaneous and task-related thoughts , 2010, Quarterly journal of experimental psychology.

[77]  Jennifer A. Silvers,et al.  Age-related differences in emotional reactivity, regulation, and rejection sensitivity in adolescence. , 2012, Emotion.

[78]  Wolfgang Grodd,et al.  Principles of a brain-computer interface (BCI) based on real-time functional magnetic resonance imaging (fMRI) , 2004, IEEE Transactions on Biomedical Engineering.

[79]  Adrian Angold,et al.  Development of a Short Questionnaire for Use in Epidemiological Studies of Depression in Children and Adolescents: Factor Composition and Structure Across Development. , 1995 .

[80]  Amir Shmuel,et al.  Partial Correlation-Based Retinotopically Organized Resting-State Functional Connectivity Within and Between Areas of the Visual Cortex Reflects More Than Cortical Distance , 2016, Brain Connect..

[81]  J. Os,et al.  An updated and conservative systematic review and meta-analysis of epidemiological evidence on psychotic experiences in children and adults: on the pathway from proneness to persistence to dimensional expression across mental disorders , 2012, Psychological Medicine.

[82]  Rainer Goebel,et al.  Neurofeedback: A promising tool for the self-regulation of emotion networks , 2010, NeuroImage.

[83]  Christian Paret,et al.  Down-regulation of amygdala activation with real-time fMRI neurofeedback in a healthy female sample , 2014, Front. Behav. Neurosci..

[84]  M. Maroun,et al.  The Role of the Medial Prefrontal Cortex-Amygdala Circuit in Stress Effects on the Extinction of Fear , 2007, Neural plasticity.

[85]  T. Hendler,et al.  Live from the "regulating brain": Harnessing the brain to change emotion. , 2020, Emotion.

[86]  Jennifer S. Beer,et al.  Prefrontal involvement in the regulation of emotion: convergence of rat and human studies , 2006, Current Opinion in Neurobiology.

[87]  D. A. Lewis,et al.  Changes in the adolescent brain and the pathophysiology of psychotic disorders. , 2014, The lancet. Psychiatry.

[88]  Iroise Dumontheil,et al.  Developmental Differences in the Control of Action Selection by Social Information , 2012, Journal of Cognitive Neuroscience.