The Nemo Real-Time Fmri Neurofeedback Study: Protocol of a Randomised Controlled Clinical Intervention Trial in the Neural Foundations of Mother–Infant Bonding
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Open access Protocol BMJ Open: first published as 10.1136/bmjopen-2018-027747 on 16 July 2019. Downloaded from The NeMo real-time fMRI neurofeedback study: protocol of a randomised controlled clinical intervention trial in the neural foundations of mother–infant bonding Monika Eckstein,1 Anna-Lena Zietlow,1 Martin Fungisai Gerchen,2,3 Mike Michael Schmitgen,4 Sarah Ashcroft-Jones,1 Peter Kirsch,2,3 Beate Ditzen1 To cite: Eckstein M, ABSTRACT Strengths and limitations of this study Zietlow A-L, Gerchen MF, et al. Introduction Most mothers feel an immediate, The NeMo real-time fMRI strong emotional bond with their newborn. On a ► The novelty of used methods allows the investiga- neurofeedback study: protocol neurobiological level, this is accompanied with the of a randomised controlled tion of the effect of real-time functional MRI (rtfMRI) activation of the brain reward systems, including the clinical intervention trial in the neurofeedback (NFB) on maternal bonding. striatum. However, approximately 10% of all mothers neural foundations of mother– ► The study investigates the ability of rtfMRI-NFB report difficulties to bond emotionally with their infant bonding. BMJ Open to upregulate brain activity in correlation with be- 2019;9:e027747. doi:10.1136/ infant and display impaired reward responses to the havioural and biopsychological markers. bmjopen-2018-027747 interaction with their infant which might have long- ► The simultaneous investigation of two brain regions term negative effects for the child’s development. As ► Prepublication history for as well as the presence of a control group proposed this paper is available online. previous studies suggest that activation of the striatal in the methods of this protocol enables a compara- To view these files, please visit reward system can be regulated through functional tive analysis of the benefits of the rtfMRI training, as the journal online (http:// dx. doi. MRI (fMRI)-based neurofeedback (NFB), we have well as increasing clarity regarding the role of differ- org/ 10. 1136/ bmjopen- 2018- designed and investigate fMRI-NFB training to treat ential brain regions in social reward. 027747). maternal bonding difficulties. ► The proposed method, through its longitudinal de- Methods and analysis In the planned trial, mothers sign with follow-up measures, will help to evidence http://bmjopen.bmj.com/ ME and A-LZ contributed will be presented pictures of their infant and real- equally. how NFB training brings about behavioural change, time fMRI (rtfMRI), peripheral measures, neural, in turn allowing for better understanding of the po- ME and A-LZ are shared first endocrine, psychophysiological and behavioural tential applications, predictive neural signatures and authors. measures will be assessed. Mothers with bonding participant criteria crucial for the success of rtfMRI. difficulties (n=68) will be randomised to one of two ► Due to the statistical co-occurrence of mater- Received 13 November 2018 double-blind intervention groups at 4–6 months nal bonding difficulties and postpartum depression Revised 22 March 2019 postpartum. They will participate in three repeated and the similar pattern of muted reward respons- Accepted 22 May 2019 NFB training sessions with rtfMRI-NFB training to es in both instances, the explanatory power of increase activation of (a) the ventral striatum or (b) the results of the rtfMRI-NFB intervention may be on October 1, 2021 by guest. Protected copyright. the anterior cingulate. Interview data and real-time confounded. mother–infant interaction behaviour pre-intervention, post-intervention and at follow-up will serve as clinical outcome measures. INTRODUCTION © Author(s) (or their Ethics and dissemination Study procedures are employer(s)) 2019. Re-use in line with the recommendations of the World Neurobiological, emotional and behavioural permitted under CC BY-NC. No Medical Association (revised Declaration of Helsinki) aspects of maternal bonding commercial re-use. See rights and were approved by the Ethics Committee of the The parental bond is the first social bond and permissions. Published by Medical Faculty, s-450/2017, Heidelberg University. that infants experience in life. Usually, it is BMJ. All participants will provide written informed the mother who serves as the infant’s imme- For numbered affiliations see consent after receiving a detailed oral and written end of article. diate and most central social interaction explanation of all procedures and can withdraw their partner. Maternal bonding is reflective of the Correspondence to consent at any time without negative consequence. first emotional bond that a mother gradu- Dr Monika Eckstein; Results will be internationally published and ally develops with her infant, within the first monika. eckstein@ med. uni- disseminated, to further the discussion on non- weeks postpartum, and is characterised by heidelberg. de and Dr. Anna- pharmacological treatment options in complex positive feelings, emotional warmth and affec- Lena Zietlow; mental disorders. tion towards the infant.1 In the eyes of some anna- lena. zietlow@ med. uni- Trial registration number DRKS00014570; Pre-results. heidelberg. de researchers, maternal bonding represents Eckstein M, et al. BMJ Open 2019;9:e027747. doi:10.1136/bmjopen-2018-027747 1 Open access one of the most important psychological processes that Depression during the postpartum period itself is BMJ Open: first published as 10.1136/bmjopen-2018-027747 on 16 July 2019. Downloaded from gradually enfold after birth2 and is a significant and generally characterised by loss of interest or joylessness, central aspect of the emerging relationship between insomnia, feelings of guilt, difficulties concentrating mother and infant.3 and, in severe cases, suicidal tendencies. Intense feel- The initial period after birth is also known as the ings and self-blame about being a bad mother are also ‘Baby-Honeymoon’, a state of euphoria and happiness often reported.20 On a neurobiological level, postpartum fuelled by the desire to constantly be near and to ‘fall in depression relates to a reduced level of reactivity in the love’ with the infant, which allows the mother to take on striatal reward system, for example in the putamen,21 but the challenges of the adaptation to parenthood. In this also the amygdala network22 together with endocrine way, maternal bonding also fulfils a biological function changes in the serotonin and steroid systems.23 Studies by ensuring the care for and subsequent survival of the show that in particular the mother–infant relationship,24 25 newborn.4 On the behavioural level, maternal bonding as well as the actual mother–infant interaction,26 both emerges through touch, eye-contact, use of ‘motherese’ short term and long term can be impaired by peripartum and the smiling at or caressing of the infant.5 Maternal and postpartum depression.24 27 Results of a recent study bonding can therefore said to be expressed in the care- suggest that the link between maternal depressive symp- giving behaviours of the parent, in their focus on and high toms at 2 months postpartum and maternal report about level of sensitivity to the needs of the infant.6 On the other interaction with the infant at 6 months was mediated hand, maternal bonding is also formed in the mother’s by maternal feelings of attachment.28 The present study emotions and thoughts about the infant and in the mental focuses on bonding impairments, rather than postpartum representations of motherhood that the mother holds.7 depression, although there will be inevitable co-occur- The strength of maternal bonding can also be demon- rence in the participant sample. strated on a neurobiological level.8 Central structures such Research indicates that experiences and interaction as the striatum, ventral tegmental area, amygdala, septum in the ‘sensitive’ postpartum period have long-term and hypothalamus are involved in affiliative behaviour, consequences for the cognitive as well as socio-emo- together with a combination of neurotransmitters and tional development in children.24 29 Animal studies have modulators such as dopamine and oxytocin.9 10 For affilia- also demonstrated that positive caring behaviours of tive traits, it has been proposed that those are mediated by the mother positively influence offspring brain develop- dopaminergic projections from the ventral tegmental area ment and long-term stress-coping behaviours even in the and endogenous opioids in the hypothalamus with projec- next generation via epigenetic changes.30 Conversely, in tions to the septum, especially during physical contact11 humans, decreased maternal bonding can result in higher that underlie rewarding feelings of affiliation. rates of self-directed affect regulation strategies and One finding of central relevance to maternal bonding increased stress reactivity31 of the infant, as well as vari- in particular is that mothers who report a good emotional able self-comfort behaviours, moderated by the infant’s http://bmjopen.bmj.com/ bonding to their infant show increased reward-related gender and age.31 Research also indicates that restrained activation in dopaminergic brain regions (the nucleus (distant) maternal behaviour can have far-reaching nega- accumbens in the ventral striatum) in response to infant tive consequences for self-regulation, social behaviour and stimuli.12 These effects are particularly evident in the stress management in the infant24 29 even into adulthood mother, in comparison to other caregivers, and have