Neuroimaging of ADHD: From matter over mind to mind over matter
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1
King's College London, Child & Adolescent Psychiatry, United Kingdom
The last two decades of neuroimaging of ADHD have shown consistent deficits in the structure, function and chemistry of the brain. Cognitively, ADHD patients suffer from deficits in “cool “and “hot” executive functions, most prominently in tasks of attention, inhibition, timing and motivation control. Our most recent structural meta-analysis shows that ADHD children and adults suffer from reduced structure in the right basal ganglia and insula as well as ventromedial orbitofrontal cortex (Norman et al., 2016). This parallels our meta-analysis of positron emission tomography (PET) studies that shows that medication-naïve adult ADHD patients have reduced dopamine transporter levels in the basal ganglia, in line with evidence for reduced striatal dopamine levels (Fusar-Poli et al., 2011). Our meta-analyses of functional magnetic resonance imaging (fMRI) studies show cognitive domain-specific deficits in several dissociated fronto-striato-parietal and fronto-parieto-cerebellar networks during tasks of inhibitory control (inferior fronto-striatal networks) (Hart et al., 2013, Norman et al., 2016), attention (dorsal fronto-striato-parietal networks) (Hart et al., 2013) and timing functions (inferior fronto-parieto-cerebellar networks) (Hart et al., 2012). There is also emerging evidence for deficits in dopaminergically innervated “hot” executive function networks, such as motivation control networks (Plichta & Scheres et al., 2014). Furthermore, apart from poor activation of task-relevant networks, there is evidence for reduced deactivation of the default more network in ADHD, and both, the poor activation of task-relevant networks and the poor ability to “switch off” of the default mode network, presumably reflecting increased mind wandering, appears to be associated with poor cognitive performance (Christakou et al., 2013). Furthermore, some of these structural and neurofunctional deficits are disorder-specific relative to patients with OCD (Norman et al., 2016), with conduct disorder (Rubia, 2011, Alegria et al., 2016) and with autism. The most prominent disorder-specific deficits compared to these other childhood disorders are the functional deficits in right inferior frontal cortex/insula (Rubia, 2011, Norman et al., 2016) and the structural deficits in basal ganglia and insula (Norman et al., 2016). Our meta-analyses of the effects of acute and long-term stimulant medication -the benchmark treatment for ADHD -on the function of the ADHD brain shows most prominent upregulation effects in these very regions such as right inferior frontal cortex/insula (Rubia et al., 2014, Norman et al., 2014). An exciting new avenue is to test the concept of mind over matter in the form of real-time fMRI-Neurofeedback in ADHD of these very brain regions that are most consistently underfunctioning, disorder-specific and consistently upregulated with stimulant medication, such as right inferior frontal cortex. For this purpose, we conducted a proof of concept randomised controlled trial in 31 adolescents with ADHD, teaching them to self-upregulate the right inferior frontal cortex (N = 18 , active group) or the left parahippocampal gyrus (N = 13, control group) in 14 sessions of 8 minutes of real-time fMRI Neurofeedback. The main clinical outcome measures were parent rated ADHD symptom severity measures. In addition we acquired pre and post measures of cognitive tasks that are mediated by right inferior prefrontal cortex such as inhibition, attention and timing functions, and fMRI activation during a motor inhibition task that typically elicits reduced inferior frontal activation. We also tested transfer effects (without feedback) and longer-term follow-up effects 11 months later. Both NF groups showed significantly linearly progressive increased activation with increasing session numbers in their respective target regions relative to the other group. Both groups also showed reduced ADHD symptoms from pre to post with no significant group differences; these changes, furthermore correlated significantly with the brain changes in their respective target regions. Only the active group, however, showed a transfer effect, whereby they showed increased activation in rIFC without the neurofeedback. Also, only the active group maintained the achieved improvements in ADHD symptoms at an average of 11 month follow-up. Furthermore, only the active group improved in intra-subject response variability and (trend-wise) in sustained attention. Lastly, only the active group showed significantly enhanced rIFC activation after the training relative to before the training during a Stop motor inhibition task, relative to the control group, who did not show this effect. The rIFC upregulation effect was similar to the one we have previously observed with stimulant medication (Rubia et al., 2014). The proof of concept study shows that mind over matter is possible in ADHD whereby ADHD adolescents can learn to self-up-regulate a brain region that is consistently and disorder-specifically impaired and modulated by stimulant medication. The self-upregulation of this right inferior frontal activation furthermore is associated with improved ADHD symptoms, cognition and inhibitory rIFC activation. Future studies will have to replicate the findings against sham neurofeedback.
References
Alegria A, Radua J, Rubia K (2016) A meta-analysis of functional magnetic resonance imaging studies of disruptive behavior disorders. Am J Psychiatry, in press. Christakou A, Murphy C, Chantiluke K, Cubillo A,Smith AB, Daley, E, Ecker, C, Giampietro V, Murphy, D, Rubia, K (2013) Disorder-specific functional abnormalities during sustained attention in youth with Attention Deficit Hyperactivity Disorder (ADHD) and with Autism. Mol Psych, 8(2):236-44
Fusar-Poli, P, Rubia K, Rossi G, Sartori G, Ballotin U (2012) Striatal dopamine transporter alterations in ADHD: Pathophysiology of adaptation to psychostimulants? A meta-analysis. American J Psychiatry, 2012;169:264 –272
Hart H, Radua J, Mataix D, Rubia K (2012) Meta-analysis of fMRI studies of timing functions in ADHD. Neuroscience Biobehavioural Review, 36(10): 2248-2256.
Hart H, Radua J, Mataix D, Rubia K (2013) Meta-analysis of fMRI studies of inhibition and attention in ADHD: exploring task-specific, stimulant medication and age effects. JAMA Psychiatry 70(2):185-98
Norman, L, Carlisi, C, Lukito S, Hart H, Mataix-Cols, Radua J, D, Rubia, K (2016) A comparative meta-analysis of structural and functional brain abnormalities in ADHD and OCD. JAMA Psychiatry, doi: 10.1001/jamapsychiatry.2016.0700. Epub ahead of print.
Plichta MM, Scheres A. Ventral-striatal responsiveness during reward anticipation in ADHD and its relation to trait impulsivity in the healthy population: A meta-analytic review of the fMRI literature. Neuroscience Biobehavioural Review. 2014;38:125-34.
Rubia K. (2011). “Cool” inferior fronto-cerebellar dysfunction in Attention Deficit Hyperactivity Disorder (ADHD) versus “hot” ventromedial orbitofronto-limbic dysfunction in conduct disorder. Biological Psychiatry, 2011; 69: e69–e87.
Rubia K, Alzamora A, Smith ABS, Cubillo A, Brammer M, Radua Q (2014): Effects of stimulants on brain function in ADHD: a systematic review and meta-analysis. Biological Psychiatry, 5;76(8):616-28.
Keywords:
ADHD- attention deficit disorder,
fMRI BOLD,
fMRI neurofeedback,
Inhibition (Psychology),
Obsessive-Compulsive Disorder,
Autism Spectrum Disorders,
stimulants
Conference:
SAN2016 Meeting, Corfu, Greece, 6 Oct - 9 Oct, 2016.
Presentation Type:
Oral Presentation in SAN 2016 Conference
Topic:
Oral Presentations
Citation:
Rubia
K,
Norman
L,
Lukito
S,
Alegria
A and
Wulff
M
(2016). Neuroimaging of ADHD: From matter over mind to mind over matter
.
Conference Abstract:
SAN2016 Meeting.
doi: 10.3389/conf.fnhum.2016.220.00037
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Received:
29 Jul 2016;
Published Online:
30 Jul 2016.
*
Correspondence:
Prof. Katya Rubia, King's College London, Child & Adolescent Psychiatry, London, SE5 8AF, United Kingdom, katya.rubia@kcl.ac.uk