Using Transcranial Direct Current Stimulation for the Treatment of Mood Disorders

Talk given the the Hoglund Brain Imaging Center Journal Club

Transcript

1. Using Transcranial Direct Current Stimulation for the Treatment of Mood Disorders Jake Thompson Dr. Evangelia Chrysikou
2. ‣ A noninvasive technique that involves the application of small currents (typically 1-2 mA) to the scalp for a few minutes through two surface electrodes, which can modulate cortical excitability. (Chrysikou & Hamilton, 2011, Restorative Neurology & Neuroscience; Hamilton, Chrysikou, & Coslett, 2011) Transcranial Direct Current Stimulation (tDCS)
3. Transcranial Direct Current Stimulation (tDCS) ‣ Anodal tDCS: increases cortical excitability at the stimulation site through subthreshold neuron soma depolarization. ‣ Cathodal tDCS: decreases cortical excitability at the stimulation site due to neuron soma hyperpolarization. (Nitsche et al., 2008; Stagg & Nitsche, 2011)
4. Transcranial Direct Current Stimulation (tDCS) ! ! (Chrysikou, Hamilton, Coslett, Datta, Bikson, & Thompson-Schill, 2013, Cognitive Neuroscience)
5. Electrical Field Modeling 0 0.41 V/m Electric field/Current density 33% 66% -0.41 V/m +0.41 V/m Electric field/Current density 0 LEFT SIDE VIEW RIGHT SIDE VIEW TOP VIEW !
6. tDCS & fMRI
7. Method Overview
8. Intra-Scanner tDCS
9. Intra-Scanner tDCS
10. intra-scanner tDCS
11. a few examples
12. tDCS had significant behavioral and regionally specific neural facilitation effects. Furthermore, faster naming responses correlated with decreased BOLD signal in Broca’s area. The data support the importance of Broca’s area within the normal naming network and as such indicate that Broca’s area may be a suitable candidate site for tDCS in neurorehabilitation of anomic patients, whose brain damage spares this region
13. The effects of a-tDCS on EPI data from a tDCS and fMRI control study illustrating the null effect of the anode electrode on the quality of the EPI images during each functional run.
15. Improved word-retrieval during atDCS was paralleled by selectively reduced task-related activation in the left ventral IFG, an area specifically implicated in semantic retrieval processes. Under atDCS, resting- state fMRI revealed increased connectivity of the left IFG and additional major hubs overlapping with the language network. Meinzer et al. (2012)
16. @ 1.0mA intensity: no artifacts, no excitatory or inhibitory effects (MEPs and BOLD signal may probe different physiological processes)
17. Uni- and bilateral tDCS over SM1 resulted in functional connectivity changes in widespread brain areas compared with sham stimulation both during and after stimulation. Whereas bilateral tDCS predominantly modulated changes in primary and secondary motor as well as prefrontal regions, unilateral tDCS affected prefrontal, parietal, and cerebellar areas. No direct effect was seen under the stimulating electrode in the unilateral condition. The time course of changes in functional connectivity in the respective brain areas was nonlinear and temporally dispersed.
19. tDCS and Depression ! Transcranial Direct Current Stimulation in the Treatment of Major Depression: A Meta-Analysis ! ! U. G. Kalu, C. E. Sexton, C. K. Loo, and K. P. Ebmeier Department of Psychiatry, University of Oxford !
20. The Dorsolateral Prefrontal Cortex Depression has been associated with a hypoactive left DLPFC. Unbalanced activity between left and right PFC. Can anodal tDCS increase left DLPFC activity, restoring balance?
21. Behavioral Studies The meta-analysis found that active tDCS was associated with a reduction in symptoms of about 30%.! This reduction persisted at follow-ups in studies where follow-ups were reported.! Significant heterogeneity limits the interpretability and generalizability of the findings.
22. Functional Neuromodulation of PFC Activity with tDCS in Unipolar Depression Unipolar depression is associated with negative affect, rumination, decreased motivation, and limited productivity.! Due to its massive individual and societal costs, much effort has been focused on the development of pharmacological and psychological interventions to alleviate the symptoms of depression. ! Although these treatments are effective for some patients, others fail to respond to such interventions alone.
23. A limited but growing number of studies suggest that tDCS—particularly over prefrontal cortex— holds promise for the treatment of depression and has useful characteristics such as low cost, ease of use, and reliable sham methodology ( Dell’Oso et al., 2010; Drevets, 2000; Ferrucci et al., 2009).! The optimal use of tDCS for reliable clinical benefits in depression has not been fully explored. ! We are combining tDCS and fMRI to investigate the effects of neurostimulation on frontal cortical excitability during a negative thought regulation task in depressed and healthy control subjects. Functional Neuromodulation of PFC Activity with tDCS in Unipolar Depression
25. Cognitive Reappraisal of Negative Stimuli Controls showed increased activity of the frontal pole (a), and patients showed increased activity in the right precuneous (b) Controls showed increased activity of the left frontal pole (a), and patients showed increased activity in the left orbitofrontal cortex (b & c) Pre-tDCS > Concurrent tDCS Concurrent tDCS > Pre-tDCS
26. Cognitive Reappraisal of Negative Stimuli During concurrent tDCS over the DLPFC patients increased activation of the left inferior frontal gyrus Patients > Controls
27. Effect of tDCS in Depressed Patients Even during ‘look only’ trails, patients showed increased activation of the left orbitofrontal cortex during anodal stimulation Concurrent tDCS > Pre-tDCS
28. What does it all mean? Findings suggest that anodal stimulation does alter cortical excitability in a manner that can be captured with fMRI.! Anodal stimulation is related to different activation patterns in depressed patients and controls.! Protocol Considerations:! Larger groups may help clean up behavioral comparisons. Increase current from 1.5mA?
29. Next Steps Large scale studies to determine optimal protocol.! Larger samples to investigate tDCS using fMRI.! Examine interactions between tDCS and other depression treatments (psychopharmacology)! Longitudinal studies to examine lasting effects, relapse rates, etc.