Effects of mindfulness-based cognitive therapy on neurophysiological correlates of performance monitoring in adult attention-deficit/hyperactivity disorder

https://doi.org/10.1016/j.clinph.2013.11.031Get rights and content

Highlights

  • Mindfulness-based cognitive therapy (MBCT) suggests enacting comparable neurophysiological effects related to attention and self-regulation as pharmacological treatments for ADHD.

  • Enhanced error-positivity (Pe) amplitudes indexing error saliency/awareness were associated with ameliorated inattention symptoms.

  • Increased NoGo-P3 amplitude reflecting greater inhibitory control correlated with attenuated hyperactivity/impulsivity symptomatology.

Abstract

Objective

To examine whether mindfulness-based cognitive therapy (MBCT) would enhance attenuated amplitudes of event-related potentials (ERPs) indexing performance monitoring biomarkers of attention-deficit/hyperactivity disorder (ADHD).

Methods

Fifty adult ADHD patients took part in a randomised controlled study investigating ERP and clinical measures pre-to-post MBCT. Twenty-six patients were randomly allocated to MBCT, 24 to a wait-list control. Main outcome measures included error processing (ERN, Pe), conflict monitoring (NoGo-N2), and inhibitory control (NoGo-P3) ERPs concomitant to a continuous performance task (CPT-X). Inattention and hyperactivity–impulsivity ADHD symptoms, psychological distress and social functioning, and mindfulness skills were also assessed.

Results

MBCT was associated with increased Pe and NoGo-P3 amplitudes, coinciding with reduced ‘hyperactivity/impulsivity’ and ‘inattention’ symptomatology. Specific to the MBCT; enhanced Pe amplitudes correlated with a decrease in hyperactivity/impulsivity symptoms and increased ‘act-with-awareness’ mindfulness skill, whereas, enhanced P3 correlated with amelioration in inattention symptoms.

Conclusions

MBCT enhanced ERP amplitudes associated with motivational saliency and error awareness, leading to improved inhibitory regulation.

Significance

MBCT suggests having comparable modulation on performance monitoring ERP amplitudes as pharmacological treatments. Further study and development of MBCT as a treatment for ADHD is warranted, in addition to its potential scope for clinical applicability to broader defined externalising disorders and clinical problems associated with impairments of the prefrontal cortex.

Introduction

The human performance monitoring system synchronises flexible and adaptive goal-directed cognition and behaviour, encompassing error processing and conflict monitoring subsystems which update and modify subsequent response. Neural substrates of this complex network are multi-levelled and interdependent, although predominantly postulated within the region of the prefrontal cortex (PFC), specifically the dorsal anterior cingulate cortex (ACC) (Botvinick et al., 2004), and purported to be heavily involved in self-monitoring and self-regulation.

Increased dopaminergic system activity in the ACC correlates with electro-cortical amplitude increases in the early (50–150 ms) error-related negativity (ERN) and later (200–400 ms) positive voltage, error-positivity (Pe) event-related potentials (ERPs) (Holroyd and Coles, 2002, Biehl et al., 2011), evoked in response to conscious detection of error-making. Controversy exists regarding the functional significance of the ERN; whether it reflects activation of the error detection system to mismatch (Gehring et al., 1993) and corresponding correct-related negativity (CRN) (Vidal et al., 2000); a global conflict monitoring system activated by error vs. correct response choice (Yeung et al., 2004a); emotional response to making a known error (Luu et al., 2000); or more likely the interplay between cognitive and affective dynamics in error processing (Yeung, 2004b). The Pe generally reflects awareness of a committed error (Nieuwenhuis et al., 2001, Overbeek, 2005, Shalgi et al., 2009), implying a greater degree of affective evaluation to error significance compared to the ERN (Falkenstein, 2004). Impairments in performance monitoring are proposed to underlie symptoms of attention-deficit/hyperactivity disorder (ADHD) (Shiels and Hawk, 2010), supported by the clinical efficacy of methylphenidate-based pharmacology (Sunohara et al., 1999) which increase catecholamine release, such as dopamine (Missale et al., 1998).

Furthermore, depleted prefrontal cerebral dopamine, via branched chain amino acids (BCAAs) ingestion, has shown to attenuate N2 and P3 ERP component amplitudes (Neuhaus et al., 2009). The N2 (150–400 ms) reflects global performance monitoring processes associated with attention and motor response preparation (Eimer et al., 1996, Donkers and van Boxtel, 2004). Specifically, increased amplitude of the NoGo-N2 (evoked when a response is made for ‘NoGo’ stimuli) has been associated with increased conflict monitoring (Donkers and van Boxtel, 2004), and response inhibition (Falkenstein et al., 1999, Nieuwenhuis et al., 2004). The NoGo-P3 (300–500 ms) reflects a ‘closure’ potential of this inhibitory gating response circuit, exclusive to response inhibition execution (Donkers and van Boxtel, 2004). Attenuated ERN, Pe, NoGo-N2 and NoGo-P3 amplitudes evoked during tasks examining performance monitoring have been found in children (Albrecht et al., 2008, Senderecka et al., 2011) and adults (Prox et al., 2007, McLoughlin et al., 2009) with ADHD and other externalising problems (Sokhadze et al., 2008, Ruchsow et al., 2005, Franken et al., 2007, Brazil et al., 2009), representing biomarkers which subsequently ‘normalise’ when treated with pharmacology, targeting neurotransmission (Sunohara et al., 1999). Pharmacological treatments have limitations however, as average response rates are often lower in adults compared to children alongside related safety issues of medication abuse/addiction, and an overall lack of evidence for long-term treatment effects.

Mindfulness-based cognitive therapy (MBCT) is the coalescence of cognitive behavioural therapy (CBT) and mindfulness; a form of sustained attention training. Proposals subsume MBCT’s therapeutic working pathways into: (a) attention regulation, (b) emotion regulation, (c) somatic awareness, (d) distancing from a self-focused perspective (Hölzel et al., 2011). Gaining a more sophisticated conscious relational understanding and active control of such internal domains during MBCT enhances cognitive flexibility, acute present-moment attention and bio-regulation, enabling insight and adaptation of maladaptive cognitions and behaviours underlying psychiatric symptoms.

Extant clinical applications of MBCT point to its versatility, possibly due to its potential for multi-faceted channels of efficacy. Disorders whose aetiology and maintenance are associated with dysfunctional fronto-limbic PFC-amygdala cortical networks and consequent emotion regulation, such as depression (Kenny and Williams, 2007, van Alderen et al., 2012), suicide vulnerability (Williams et al., 2006), bipolar disorder (Williams et al., 2008), generalised anxiety disorders (Evans et al., 2008), and borderline personality disorder (Sachse et al., 2010), have shown preliminary (or with depression, more extensive) promising clinical response to MBCT. Furthermore, MBCT has shown to be on par with anti-depressant medication for relapse prevention (40–50% MBCT vs. 60% treatment-as-usual) (Teasdale et al., 2000, Ma and Teasdale, 2004, Kuyken et al., 2008, Segal et al., 2010). Attention regulation during MBCT provides a fitting rationale for its therapeutic application to ADHD. A modified protocol already indicates its feasibility for managing ADHD symptoms (Zylowska et al., 2008), warranting larger scale controlled trials. In line, non-clinical applications of intensive mindfulness training have shown to optimise response inhibition (Sahdra et al., 2011).

Parallel to treatment trials, advancing scientific knowledge of the working mechanisms of MBCT for psychiatric disorders is equally justified, contributing to improved clinical efficacy. To this regard, we were interested whether the attention training component of MBCT would have comparable therapeutic pathways as pharmacological treatments facilitating better attention regulation in ADHD (Volkow et al., 2007), via enhanced neurotransmission pathways. We hypothesised the mindfulness process would improve attention and self-regulation, examining this hypothesis using ERPs related to sustained attention and inhibitory control, further associated with ACC activity. To this end, ERPs provide reliable measures of brain function, regulated by neurotransmission (Cassidy et al., 2012). Specifically, we postulated amplitudes of ERPs pertaining to error-processing (ERN and Pe), and inhibitory processes (NoGo-N2 and NoGo-P3) would increase following exposure to MBCT, reflecting optimised performance monitoring. Furthermore, we anticipated ERP changes associated with the MBCT would improve clinical symptoms. To examine this hypothesis, correlational analyses using increment change measures of ERP, clinical, and mindfulness indexes were also conducted.

Section snippets

Sample

Sixty-one adult ADHD patients were recruited via Radboud University Nijmegen Medical Centre outpatient unit, 32 randomly allocated to the treatment condition (MBCT), and 29 to a wait-list (WL) control group. Subsequently, 11 patients (6 MBCT; 5 WL) did not attend the T2/post testing session. For two cases we dropped their participation because one did not attend the full 12-week MBCT intervention, the second started extra mindfulness training outside the intervention; and the further nine

Results

Due to the various findings analysed vs. reporting length constraints, non-significant results are not explicitly reported in the following sections.

Discussion

To our knowledge this is the first study to explore the effects of MBCT on ERP markers and related clinical amelioration in adult ADHD. Primarily, we investigated whether amplitudes of ERPs indexing performance monitoring, related to inattention and hyperactivity–impulsivity symptoms, would increase following MBCT. In accord, MBCT enhanced electro-cortical amplitudes of later evoked ERPs associated with error awareness, motivational saliency, and inhibitory control, alongside amelioration in

Summary

MBCT increased Pe and NoGo-P3 ERP amplitudes, collectively improving inhibitory gating regulation, akin to a reflexive ‘switching’ ability, associated with underlying noradrenergic-regulated global attention processes related to enhanced awareness/vigilance. In alignment, dopaminergic-regulated focused attention may not have been the principal facet by which the MBCT worked, supported by the lack of modulation on the ERN. Furthermore, improved motor and emotion regulation, reflected in

Financial support

This research was supported by BrainGain SmartMix Programme of the Netherlands Ministry of Economic Affairs and Netherlands Ministry of Education, Culture and Science.

Conflict of Interest

None.

Acknowledgements

The authors gratefully thank all those who participated in the study. We also thank Dr. Marieke Lansbergen for her input; Jan Leijtens, Andrea Loing, Myrddin Hermans, and Nada Janssen for assistance with data collection; and Geert Schattenberg for data management.

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