Anodal transcranial direct current stimulation over the left dorsolateral prefrontal cortex modulates attention and pain in fibromyalgia: randomized clinical trial

Adriana Ferreira Silva, Maxciel Zortea, Sandra Carvalho, Jorge Leite, Iraci Lucena da Silva Torres, Felipe Fregni, Wolnei Caumo, Adriana Ferreira Silva, Maxciel Zortea, Sandra Carvalho, Jorge Leite, Iraci Lucena da Silva Torres, Felipe Fregni, Wolnei Caumo

Abstract

Cognitive dysfunction in fibromyalgia patients has been reported, especially when increased attentional demands are required. Transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (DLPFC) has been effective in modulating attention. We tested the effects of a single session of tDCS coupled with a Go/No-go task in modulating three distinct attentional networks: alertness, orienting and executive control. Secondarily, the effect on pain measures was evaluated. Forty females with fibromyalgia were randomized to receive active or sham tDCS. Anodal stimulation (1 mA, 20 min) was applied over the DLPFC. Attention indices were assessed using the Attention Network Test (ANT). Heat pain threshold (HPTh) and tolerance (HPTo) were measured. Active compared to sham tDCS led to increased performance in the orienting (mean difference [MD] = 14.63) and executive (MD = 21.00) attention networks. There was no effect on alertness. Active tDCS increased HPTh as compared to sham (MD = 1.93) and HPTo (MD = 1.52). Regression analysis showed the effect on executive attention is mostly independent of the effect on pain. DLPFC may be an important target for neurostimulation therapies in addition to the primary motor cortex for patients who do not respond adequately to neurostimulation therapies.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1
Group differences (main effects) on the ANT scores based on mixed linear model analyses. A: Alerting. B: Orienting. C: Executive. *P 

Figure 2

Attention network test (ANT); cues:…

Figure 2

Attention network test (ANT); cues: no cue, central cue, double cue and spatial…

Figure 2
Attention network test (ANT); cues: no cue, central cue, double cue and spatial cues; and targets: Incongruent, neutral and congruent and an example of the procedure of ANT. Left column: sequence of events per trial of the ANT; right column: possible stimuli associated with each event. Except for the spatial and invalid spatial cue (80% vs. 20% probability, respectively), all cue and flanker constellations were equally probable and appeared up or down of the fixation cross. The target and flanker remained visible on the screen until the patients respond, but for no longer than 1700 ms. While trial duration was fixed to 4000 ms, a temporal jitter was introduced by a variable delay of the cue onset (200, 300, and 400 ms after trial onset) to reduce expectancies.

Figure 3

Flowchart showing recruitment and progress…

Figure 3

Flowchart showing recruitment and progress through the study.

Figure 3
Flowchart showing recruitment and progress through the study.
Figure 2
Figure 2
Attention network test (ANT); cues: no cue, central cue, double cue and spatial cues; and targets: Incongruent, neutral and congruent and an example of the procedure of ANT. Left column: sequence of events per trial of the ANT; right column: possible stimuli associated with each event. Except for the spatial and invalid spatial cue (80% vs. 20% probability, respectively), all cue and flanker constellations were equally probable and appeared up or down of the fixation cross. The target and flanker remained visible on the screen until the patients respond, but for no longer than 1700 ms. While trial duration was fixed to 4000 ms, a temporal jitter was introduced by a variable delay of the cue onset (200, 300, and 400 ms after trial onset) to reduce expectancies.
Figure 3
Figure 3
Flowchart showing recruitment and progress through the study.

References

    1. Volz MS, Suarez-Contreras V, Portilla ALS, Fregni F. Mental imagery-induced attention modulates pain perception and cortical excitability. BMC Neurosci. 2015;16:15. doi: 10.1186/s12868-015-0146-6.
    1. Julien N, Goffaux P, Arsenault P, Marchand S. Widespread pain in fibromyalgia is related to a deficit of endogenous pain inhibition. Pain. 2005;114:295–302. doi: 10.1016/j.pain.2004.12.032.
    1. Caumo W, et al. Cross-Cultural Adaptation and Validation of the Profile of Chronic Pain: Screen for a Brazilian Population. Pain Med. 2013;14:52–61. doi: 10.1111/j.1526-4637.2012.01528.x.
    1. Dall’Agnol L, et al. Repetitive transcranial magnetic stimulation increases the corticospinal inhibition and the brain-derived neurotrophic factor in chronic myofascial pain syndrome: An explanatory double-blinded, randomized, sham-controlled trial. J. Pain. 2014;15:845–855. doi: 10.1016/j.jpain.2014.05.001.
    1. Derbyshire SWG, Whalley MG, Oakley DA. Fibromyalgia pain and its modulation by hypnotic and non-hypnotic suggestion: An fMRI analysis. Eur. J. Pain. 2009;13:542–550. doi: 10.1016/j.ejpain.2008.06.010.
    1. Glass JM. Cognitive dysfunction in fibromyalgia and chronic fatigue syndrome: new trends and future directions. Curr. Rheumatol. Rep. 2006;8:425–429. doi: 10.1007/s11926-006-0036-0.
    1. Resat iliser, B. K. Cognitive Complaints in Patients with Fibromyalgia Versus Older-Aged Women: Case Control Study. J. Psychiatry18 (2015).
    1. Glass JM. Review of Cognitive Dysfunction in Fibromyalgia: A Convergence on Working Memory and Attentional Control Impairments. Rheum. Dis. Clin. North Am. 2009;35:299–311. doi: 10.1016/j.rdc.2009.06.002.
    1. Langner R, Eickhoff SB. Sustaining attention to simple tasks: A meta-analytic review of the neural mechanisms of vigilant attention. Psychol. Bull. 2013;139:870–900. doi: 10.1037/a0030694.
    1. Miró E, et al. Attentional deficits in fibromyalgia and its relationships with pain, emotional distress and sleep dysfunction complaints. Psychol. Health. 2011;26:765–780. doi: 10.1080/08870446.2010.493611.
    1. Posner MI, Petersen SE. The attention systems of the human brain. Annu. Rev. Neurosci. 1990;13:25–42. doi: 10.1146/annurev.ne.13.030190.000325.
    1. Fan J, Mccandliss BD, Sommer T, Raz A, Posner MI. Testing the efficiency and independence of attentional networks. J. Cogn. Neurosci. 2002;14:340–347. doi: 10.1162/089892902317361886.
    1. Fan J, Mccandliss BD, Fossella J, Flombaum JI, Posner MI. The activation of attentional networks. Neuroimage. 2005;26:471–479. doi: 10.1016/j.neuroimage.2005.02.004.
    1. Fregni F, et al. Regulatory Considerations for the Clinical and Research Use of Transcranial Direct Current Stimulation (tDCS): review and recommendations from an expert panel. Clin. Res. Regul. Aff. 2015;32:22–35. doi: 10.3109/10601333.2015.980944.
    1. Boggio PS, Rocha RR, da Silva MT, Fregni F. Differential modulatory effects of transcranial direct current stimulation on a facial expression go-no-go task in males and females. Neurosci. Lett. 2008;447:101–105. doi: 10.1016/j.neulet.2008.10.009.
    1. Marlow NM, Bonilha HS, Short EB. Efficacy of transcranial direct current stimulation and repetitive transcranial magnetic stimulation for treating fibromyalgia syndrome: a systematic review. Pain Pract. 2013;13:131–45. doi: 10.1111/j.1533-2500.2012.00562.x.
    1. Zhu, C. E. et al. Effiectiveness and safety of transcranial direct current stimulation in fibromyalgia: A systematic review and meta-analysis. J Rehabil Med 2–9, doi:10.2340/16501977-2179 (2016).
    1. Coffman BA, Clark VP, Parasuraman R. Battery powered thought: Enhancement of attention, learning, and memory in healthy adults using transcranial direct current stimulation. Neuroimage. 2014;85:895–908. doi: 10.1016/j.neuroimage.2013.07.083.
    1. Leite J, Carvalho S, Fregni F, Boggio PS, Gonçalves ÓF. The effects of cross-hemispheric dorsolateral prefrontal cortex transcranial direct current stimulation (tDCS) on task switching. Brain Stimul. 2013;6:660–667. doi: 10.1016/j.brs.2012.10.006.
    1. Carvalho S, et al. Transcranial direct current stimulation based metaplasticity protocols in working memory. Brain Stimul. 2015;8:289–294. doi: 10.1016/j.brs.2014.11.011.
    1. Brunoni, A., Boggio, P. & Fregni, F. In Neuromodulação terapêutica: Princípios e avanços da estimulação cerebral não invasiva em neurologia, reabilitação, psiquiatria e neuropsicologia (eds Fregni, F., Boggio, P. & Brunoni, A.) 3–20 (Sarvier, 2011).
    1. Cosmo C, et al. A Randomized, Double-Blind, Sham-Controlled Trial of Transcranial Direct Current Stimulation in Attention-Deficit/Hyperactivity Disorder. PLoS One. 2015;10:e0135371. doi: 10.1371/journal.pone.0135371.
    1. Andrews SC, Hoy KE, Enticott PG, Daskalakis ZJ, Fitzgerald PB. Improving working memory: The effect of combining cognitive activity and anodal transcranial direct current stimulation to the left dorsolateral prefrontal cortex. Brain Stimul. 2011;4:84–89. doi: 10.1016/j.brs.2010.06.004.
    1. Barbey AK, Colom R, Grafman J. Dorsolateral prefrontal contributions to human intelligence. Neuropsychologia. 2013;51:1361–1369. doi: 10.1016/j.neuropsychologia.2012.05.017.
    1. Mostofsky SH, et al. fMRI evidence that the neural basis of response inhibition is task-dependent. Cogn. Brain Res. 2003;17:419–430. doi: 10.1016/S0926-6410(03)00144-7.
    1. Lorenz J, Minoshima S, Casey KL. Keeping pain out of mind: The role of the dorsolateral prefrontal cortex in pain modulation. Brain. 2003;126:1079–1091. doi: 10.1093/brain/awg102.
    1. Ka CO, Moldofsky H. Sleep, daytime symptoms, and cognitive performance in patients with fibromyalgia. J. Rheumatol. 1997;24:2014–2023.
    1. Dick BD, Verrier MJ, Harker TK, Rashiq S. Disruption of cognitive function in Fibromyalgia Syndrome☆. Pain. 2008;139:610–616. doi: 10.1016/j.pain.2008.06.017.
    1. Posner MI, Rothbart MK. Research on attention networks as a model for the integration of psychological science. Annu. Rev. Psychol. 2007;58:1–23. doi: 10.1146/annurev.psych.58.110405.085516.
    1. Leite J, Carvalho S, Fregni F, Gonçalves ÓF. Task-specific effects of tDCS-induced cortical excitability changes on cognitive and motor sequence set shifting performance. PLoS One. 2011;6:1–9.
    1. Callejas A, Lupianez J, Tudela P. The three attentional networks: on their independence and interactions. Brain Cogn. 2004;54:225–227. doi: 10.1016/j.bandc.2004.02.012.
    1. Sephton SE, Studts JL, Hoover K, Weissbecker I, Lynch G, Ho I, McGuffin S, Salmon P. Biological and psychological factors associated with memory function in fibromyalgia syndrome. Heal. Psychol. 2003;22:592–7. doi: 10.1037/0278-6133.22.6.592.
    1. Wood PB. Fibromyalgia syndrome: A central role for the hippocampus – A Theoretical construct. J. Musculoskelet. Pain. 2004;12:19–26. doi: 10.1300/J094v12n01_04.
    1. Liston C, et al. Stress-Induced Alterations in Prefrontal Cortical Dendritic Morphology Predict Selective Impairments in Perceptual Attentional Set-Shifting. J. Neurosci. 2006;26:7870–7874. doi: 10.1523/JNEUROSCI.1184-06.2006.
    1. Napadow V, et al. Intrinsic brain connectivity in fibromyalgia is associated with chronic pain intensity. Arthritis Rheum. 2010;62:2545–2555. doi: 10.1002/art.27497.
    1. Napadow V, Kim J, Clauw DJ, Harris RE. Decreased intrinsic brain connectivity is associated with reduced clinical pain in fibromyalgia. Arthritis Rheum. 2012;64:2398–2403. doi: 10.1002/art.34412.
    1. Harris RE, et al. Pregabalin rectifies aberrant brain chemistry, connectivity, and functional response in chronic pain patients. Anesthesiology. 2013;119:1453–1464. doi: 10.1097/ALN.0000000000000017.
    1. Mansouri Fa, Tanaka K, Buckley MJ. Conflict-induced behavioural adjustment: a clue to the executive functions of the prefrontal cortex. Nat. Rev. Neurosci. 2009;10:141–52. doi: 10.1038/nrn2538.
    1. Kong J. Brain Activity Associated with Expectancy-Enhanced Placebo Analgesia as Measured by Functional Magnetic Resonance Imaging. J. Neurosci. 2006;26:381–388. doi: 10.1523/JNEUROSCI.3556-05.2006.
    1. Hsieh JC, Belfrage M, Stone-Elander S, Hansson P, Ingvar M. Central representation of chronic ongoing neuropathic pain studied by positron emission tomography. Pain. 1995;63:225–236. doi: 10.1016/0304-3959(95)00048-W.
    1. Valet M, et al. Patients With Pain Disorder Show Gray-Matter Loss in Pain-Processing Structures: A Voxel-Based Morphometric Study. Psychosom. Med. 2009;71:49–56. doi: 10.1097/PSY.0b013e31818d1e02.
    1. Vaseghi B, Zoghi M, Jaberzadeh S. Does anodal transcranial direct current stimulation modulate sensory perception and pain? A meta-analysis study. Clin. Neurophysiol. 2014;125:1847–1858. doi: 10.1016/j.clinph.2014.01.020.
    1. da Silva NRJ, et al. Combined neuromodulatory interventions in acute experimental pain: assessment of melatonin and non-invasive brain stimulation. Front. Behav. Neurosci. 2015;9:77. doi: 10.3389/fnbeh.2015.00077.
    1. Fregni F, et al. Regulatory Considerations for the Clinical and Research Use of Transcranial Direct Current Stimulation (tDCS): review and recommendations from an expert panel. Clin Res Regul Aff. 2016;32:22–35. doi: 10.3109/10601333.2015.980944.
    1. O’Connell, N. E., Wand, B. M., Marston, L., Spencer, S. & Desouza, L. H. Non-invasive brain stimulation techniques for chronic pain. Cochrane Database Syst. Rev. 1–74, doi:10.1002/14651858.CD008208.pub2 (2010).
    1. Boggio PS, Rocha RR, da Silva MT, Fregni F. Differential modulatory effects of transcranial direct current stimulation on a facial expression go-no-go task in males and females. Neurosci. Lett. 2008;447:101–105. doi: 10.1016/j.neulet.2008.10.009.
    1. Wager TD. Expectations and anxiety as mediators of placebo effects in pain. Pain. 2005;115:225–226. doi: 10.1016/j.pain.2005.03.018.
    1. Eippert F, Finsterbusch J, Bingel U, Büchel C. Direct evidence for spinal cord involvement in placebo analgesia. Science (80-.). 2009;326:404. doi: 10.1126/science.1180142.
    1. Nitsche Ma, Nitsche Ma, Paulus W, Paulus W. Excitability changes induced in the human motor cortex by weak transcranial direct current stimulation. J. Physiol. 2000;527(Pt 3):633–9. doi: 10.1111/j.1469-7793.2000.t01-1-00633.x.
    1. Stagg CJ, Johansen-Berg H. Studying the effects of transcranial direct-current stimulation in stroke recovery using magnetic resonance imaging. Front. Hum. Neurosci. 2013;7:1–8. doi: 10.3389/fnhum.2013.00857.
    1. Craig aDB. Emotional moments across time: a possible neural basis for time perception in the anterior insula. Philos. Trans. R. Soc. Lond. B. Biol. Sci. 2009;364:1933–42. doi: 10.1098/rstb.2009.0008.
    1. DaSilva, A. F., Volz, M. S., Bikson, M. & Fregni, F. Electrode positioning and montage in transcranial direct current stimulation. J. Vis. Exp. e2744, doi:10.3791/2744 (2011).
    1. Polanía R, Paulus W, Antal A, Nitsche MA. Introducing graph theory to track for neuroplastic alterations in the resting human brain: A transcranial direct current stimulation study. Neuroimage. 2011;54:2287–2296. doi: 10.1016/j.neuroimage.2010.09.085.
    1. Datta A, Truong D, Minhas P, Parra LC, Bikson M. Inter-individual variation during transcranial direct current stimulation and normalization of dose using MRI-derived computational models. Front. Psychiatry. 2012;3:1–8. doi: 10.3389/fpsyt.2012.00091.
    1. Castillo-Saavedra L, et al. Clinically Effective Treatment of Fibromyalgia Pain With High-Definition Transcranial Direct Current Stimulation: Phase II Open-Label Dose Optimization. J. Pain. 2016;17:14–26. doi: 10.1016/j.jpain.2015.09.009.
    1. Wolfe F, et al. The American College of Rheumatology preliminary diagnostic criteria for fibromyalgia and measurement of symptom severity. Arthritis Care Res. 2010;62:600–610. doi: 10.1002/acr.20140.
    1. Bennett R. Fibromyalgia: present to future. Curr. Rheumatol. Rep. 2004;7:371–376. doi: 10.1007/s11926-005-0022-y.
    1. Garavan H, Ross TJ, Stein EA. Right hemispheric dominance of inhibitory control: an event-related functional MRI study. Proc. Natl. Acad. Sci. USA. 1999;96:8301–8306. doi: 10.1073/pnas.96.14.8301.
    1. Bertolazi AN, et al. Validation of the Brazilian Portuguese version of the Pittsburgh Sleep Quality Index. Sleep Med. 2011;12:70–75. doi: 10.1016/j.sleep.2010.04.020.
    1. Gorenstein, C., Pang, W., Argimon, I. & Werlang, B. Manual do Inventário de depressão de Beck - BDI-II. (Casa do Psicólogo, 2011).
    1. Amorim P. Mini International Neuropsychiatric Interview (MINI): validação de entrevista breve para diagnóstico de transtornos mentais. Rev. Bras. Psiquiatr. 2000;22:106–115. doi: 10.1590/S1516-44462000000300003.
    1. Marques AP, et al. Validação da versão Brasileira do Fibromyalgia Impact Questionnaire (FIQ) Rev. Bras. Reumatol. 2006;46:24–31.
    1. Sehn F, et al. Cross-Cultural Adaptation and Validation of the Brazilian Portuguese Version of the Pain Catastrophizing Scale. Pain Med. 2012;13:1425–1435. doi: 10.1111/j.1526-4637.2012.01492.x.
    1. Brunoni AR, Fregni F. Clinical trial design in non-invasive brain stimulation psychiatric research. Int. J. Methods Psychiatr. Res. 2011;20:e19–e30. doi: 10.1002/mpr.338.
    1. Fan J, McCandliss BD, Sommer T, Raz A, Posner MI. Testing the Efficiency and Independence of Attentional Networks. J. Cogn. Neurosci. 2002;14:340–7. doi: 10.1162/089892902317361886.
    1. Schestatsky P, et al. Skin autonomic reactivity to thermoalgesic stimuli. Clin. Auton. Res. 2007;17:349–355. doi: 10.1007/s10286-007-0446-8.
    1. Backonja MM, et al. Value of quantitative sensory testing in neurological and pain disorders: NeuPSIG consensus. Pain. 2013;154:1807–1819. doi: 10.1016/j.pain.2013.05.047.

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe