fMRI Neurofeedback and Brain Stimulation for ADHD

Introduction: Psychostimulant medication is effective in ADHD but has side effects and limited long-term efficacy. fMRI Neurofeedback (NF) is a promising novel brain modulation therapy that can target the underlying brain dysfunctions that have been stablished in ADHD over the past 2 decades. We conducted a proof of concept fMRI-NF study in ADHD adolescents, targeting the right inferior frontal cortex (rIFC) which is consistently underactivated in ADHD children during cognitive control and is underlying the mechanism of action of psychostimulant medication (Norman et al., 2016, Rubia et al., 2014).

Methods: Thirty-one ADHD boys were randomized in a single-blind RCT to fMRI-NF (11 sessions) over 2 weeks of the rIFC (active group) or the left parahippocampal gyrus (lPHG, control group). Visual feedback was presented via a video-clip of a rocket that had to be moved to space. Main outcome measures were changes in parents’ ratings of clinical ADHD symptoms which were assessed at pre, post, and on average 11 month follow-up. A computer-based test battery and a fMRI Stop task were also used to assess NF effects on cognition and IFC brain function.

Results: Both groups showed significant linear progressive activation increase with increasing NF sessions in their respective target regions relative to the other group. Both groups also showed significant reduction of ADHD symptoms after treatment and at 11 month follow-up, with no significant group differences, but substantially larger follow-up effect sizes for the active group. Only the active group, furthermore, showed a transfer effect (increasing rIFC activation without NF), improved trend-wise in sustained attention, showed increased IFC activation during the stop task and had significant correlations between brain activation and clinical changes. The active group furthermore showed increased functional connectivity between right IFC and the basal ganglia but reduced functional connectivity with areas of the posterior default mode system. The findings suggest that fMRI-NF of a frontal region upregulates fronto-striatal networks and down regulates areas of mind-wandering in ADHD, both of which are key to the neurofunctional pathology.
Conclusions: The proof of concept study shows that rtfMRI-NF of rIFC is a feasible neurotherapy for ADHD adolescents, associated with short and longer-term symptom improvement, better attention skills and improved inhibitory brain activation. I will also review and discuss other methods of upregulation of frontal brain activity such as non-invasive brain stimulation with TMS and tDCS. Neurotherapeutics seem attractive for ADHD due to their safety and potential longer-term neuroplastic effects, which drugs cannot offer. However, they need to be thoroughly tested for short- and longer-term clinical and cognitive efficacy and their potential for individualised treatment.

References:

• 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, 73: 815-825
• 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.
• Rubia K (2018) Cognitive Neuroscience of Attention Deficit Hyperactivity Disorder (ADHD) and its clinical translation. Front Hum Neuroscience, in press.