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Feasibility of Non-invasive Brain Modulation for Management of Pain Related to Chemoradiotherapy in Patients with Advanced Head and Neck Cancer

View Article: PubMed Central - PubMed

ABSTRACT

Patients with head and neck cancer often experience a significant decrease in their quality of life during chemoradiotherapy (CRT) due to treatment-related pain, which is frequently classified as severe. Transcranial direct current stimulation (tDCS) is a method of non-invasive brain stimulation that has been frequently used in experimental and clinical pain studies. In this pilot study, we investigated the clinical impact and central mechanisms of twenty primary motor cortex (M1) stimulation sessions with tDCS during 7 weeks of CRT for head and neck cancer. From 48 patients screened, seven met the inclusion criteria and were enrolled. Electroencephalography (EEG) data were recorded before and after tDCS stimulation as well as across the trial to monitor short and long-term impact on brain function. The compliance rate during the long trial was extremely high (98.4%), and patients mostly reported mild side effects in line with the literature (e.g., tingling). Compared to a large standard of care study from our institution, our initial results indicate that M1-tDCS stimulation has a pain relief effect during the CRT that resulted in a significant attenuation of weight reduction and dysphagia normally observed in these patients. These results translated to our patient cohort not needing feeding tubes or IV fluids. Power spectra analysis of EEG data indicated significant changes in α, β, and γ bands immediately after tDCS stimulation and, in addition, α, δ, and θ bands over the long term in the seventh stimulation week (p < 0.05). The independent component EEG clustering analysis showed estimated functional brain regions including precuneus and superior frontal gyrus (SFG) in the seventh week of tDCS stimulation. These areas colocalize with our previous positron emission tomography (PET) study where there was activation in the endogenous μ-opioid system during M1-tDCS. This study provides preliminary evidence demonstrating the feasibility and safety of M1-tDCS as a potential adjuvant neuromechanism-driven analgesic therapy for head and neck cancer patients receiving CRT, inducing immediate and long-term changes in the cortical activity and clinical measures, with minimal side-effects.

No MeSH data available.


Related in: MedlinePlus

EEG signal sources changes to PFC and PreCuneus following 7 weeks of tDCS stimulation. The estimated locations of the EEG sources are marked out for each stage. The blue, red, and yellow dots indicate, respectively, the sources with possible locations at SFG, PreCuneus, and other areas. (A) Estimated signal sources before tDCS stimulation (average of week 2, 3, and 7). (B) Estimated signal sources immediately after tDCS stimulation (average of week 2, 3, and 7). (C) Estimated signal sources in pre-study visit week. (D) Estimated signal sources in week seven. (E) Estimated tDCS-induced mu-opioid activation locations (DosSantos et al., 2014).
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Figure 3: EEG signal sources changes to PFC and PreCuneus following 7 weeks of tDCS stimulation. The estimated locations of the EEG sources are marked out for each stage. The blue, red, and yellow dots indicate, respectively, the sources with possible locations at SFG, PreCuneus, and other areas. (A) Estimated signal sources before tDCS stimulation (average of week 2, 3, and 7). (B) Estimated signal sources immediately after tDCS stimulation (average of week 2, 3, and 7). (C) Estimated signal sources in pre-study visit week. (D) Estimated signal sources in week seven. (E) Estimated tDCS-induced mu-opioid activation locations (DosSantos et al., 2014).

Mentions: Figure 3 shows the clustered ICs from 5 subjects by common properties of their EEG data spectrums and scalp maps. The pre-tDCS stage had three clusters separately that included estimated functional brain regions (Week 2, 3, and 7 EEG data included): left Anterior Cingulate Cortex (ACC) and left Medial Frontal Gyrus (MFG) centered at (MNI: −15, 40, 16); left MFG and Sub-Gyral centered at (−18, −2, 59); Insula, left Precentral Gyrus (primary motor cortex), and left Superior Temporal Gyrus (STG) centered at (−47, −12, 8). The post-tDCS stage had four clusters separately and included estimated functional brain regions (Week 2, 3, and 7 EEG data included): left Superior Frontal Gyrus (SFG) centered at (−9, 12, 57); left SFG, MFG, and ACC centered at (−19, 45, 17); Extra-Nuclear and Insula centered at (−47, −12, 8); Sub-Gyral, Extra-Nuclear and Insula centered at (García-Larrea et al., 1999; Zaghi et al., 2011; Hartley et al., 2014). The pre-study visit week tDCS stage had four clusters separately and included estimated functional brain regions in: Insula, Extra-Nuclear, and Sub-Gyral centered at (40, −11, 20); left STG, Supramarginal Gyrus (somatosensory association cortex), and middle Temporal Gyrus (MTG) centered at (−44, −58, 26); left MFG centered at (6, 61, 14); left MFG centered at (−3, −11, 64). The week 7 tDCS stage had three clusters separately AND included estimated functional brain regions: Sub-Gyral, right Precentral Gyrus, Middle Frontal Gyrus, and SFG centered at (20, −20, 66); left SFG centered at (−17, 50, 50); and left Precuneus and Superior Parietal Lobule centered at (−20, −63, 49). All coordinates reported were MNI coordinates.


Feasibility of Non-invasive Brain Modulation for Management of Pain Related to Chemoradiotherapy in Patients with Advanced Head and Neck Cancer
EEG signal sources changes to PFC and PreCuneus following 7 weeks of tDCS stimulation. The estimated locations of the EEG sources are marked out for each stage. The blue, red, and yellow dots indicate, respectively, the sources with possible locations at SFG, PreCuneus, and other areas. (A) Estimated signal sources before tDCS stimulation (average of week 2, 3, and 7). (B) Estimated signal sources immediately after tDCS stimulation (average of week 2, 3, and 7). (C) Estimated signal sources in pre-study visit week. (D) Estimated signal sources in week seven. (E) Estimated tDCS-induced mu-opioid activation locations (DosSantos et al., 2014).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
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Figure 3: EEG signal sources changes to PFC and PreCuneus following 7 weeks of tDCS stimulation. The estimated locations of the EEG sources are marked out for each stage. The blue, red, and yellow dots indicate, respectively, the sources with possible locations at SFG, PreCuneus, and other areas. (A) Estimated signal sources before tDCS stimulation (average of week 2, 3, and 7). (B) Estimated signal sources immediately after tDCS stimulation (average of week 2, 3, and 7). (C) Estimated signal sources in pre-study visit week. (D) Estimated signal sources in week seven. (E) Estimated tDCS-induced mu-opioid activation locations (DosSantos et al., 2014).
Mentions: Figure 3 shows the clustered ICs from 5 subjects by common properties of their EEG data spectrums and scalp maps. The pre-tDCS stage had three clusters separately that included estimated functional brain regions (Week 2, 3, and 7 EEG data included): left Anterior Cingulate Cortex (ACC) and left Medial Frontal Gyrus (MFG) centered at (MNI: −15, 40, 16); left MFG and Sub-Gyral centered at (−18, −2, 59); Insula, left Precentral Gyrus (primary motor cortex), and left Superior Temporal Gyrus (STG) centered at (−47, −12, 8). The post-tDCS stage had four clusters separately and included estimated functional brain regions (Week 2, 3, and 7 EEG data included): left Superior Frontal Gyrus (SFG) centered at (−9, 12, 57); left SFG, MFG, and ACC centered at (−19, 45, 17); Extra-Nuclear and Insula centered at (−47, −12, 8); Sub-Gyral, Extra-Nuclear and Insula centered at (García-Larrea et al., 1999; Zaghi et al., 2011; Hartley et al., 2014). The pre-study visit week tDCS stage had four clusters separately and included estimated functional brain regions in: Insula, Extra-Nuclear, and Sub-Gyral centered at (40, −11, 20); left STG, Supramarginal Gyrus (somatosensory association cortex), and middle Temporal Gyrus (MTG) centered at (−44, −58, 26); left MFG centered at (6, 61, 14); left MFG centered at (−3, −11, 64). The week 7 tDCS stage had three clusters separately AND included estimated functional brain regions: Sub-Gyral, right Precentral Gyrus, Middle Frontal Gyrus, and SFG centered at (20, −20, 66); left SFG centered at (−17, 50, 50); and left Precuneus and Superior Parietal Lobule centered at (−20, −63, 49). All coordinates reported were MNI coordinates.

View Article: PubMed Central - PubMed

ABSTRACT

Patients with head and neck cancer often experience a significant decrease in their quality of life during chemoradiotherapy (CRT) due to treatment-related pain, which is frequently classified as severe. Transcranial direct current stimulation (tDCS) is a method of non-invasive brain stimulation that has been frequently used in experimental and clinical pain studies. In this pilot study, we investigated the clinical impact and central mechanisms of twenty primary motor cortex (M1) stimulation sessions with tDCS during 7 weeks of CRT for head and neck cancer. From 48 patients screened, seven met the inclusion criteria and were enrolled. Electroencephalography (EEG) data were recorded before and after tDCS stimulation as well as across the trial to monitor short and long-term impact on brain function. The compliance rate during the long trial was extremely high (98.4%), and patients mostly reported mild side effects in line with the literature (e.g., tingling). Compared to a large standard of care study from our institution, our initial results indicate that M1-tDCS stimulation has a pain relief effect during the CRT that resulted in a significant attenuation of weight reduction and dysphagia normally observed in these patients. These results translated to our patient cohort not needing feeding tubes or IV fluids. Power spectra analysis of EEG data indicated significant changes in α, β, and γ bands immediately after tDCS stimulation and, in addition, α, δ, and θ bands over the long term in the seventh stimulation week (p < 0.05). The independent component EEG clustering analysis showed estimated functional brain regions including precuneus and superior frontal gyrus (SFG) in the seventh week of tDCS stimulation. These areas colocalize with our previous positron emission tomography (PET) study where there was activation in the endogenous μ-opioid system during M1-tDCS. This study provides preliminary evidence demonstrating the feasibility and safety of M1-tDCS as a potential adjuvant neuromechanism-driven analgesic therapy for head and neck cancer patients receiving CRT, inducing immediate and long-term changes in the cortical activity and clinical measures, with minimal side-effects.

No MeSH data available.


Related in: MedlinePlus