CASE REPORT
Transcranial Direct Current Stimulation for Treating Depression in a Patient With Right Hemispheric Dominance A Case Study Pedro Shiozawa, MD, Mailu Enokibara da Silva, MD, and Quirino Cordeiro, MD, PhD Abstract: We report the case of a 66-year-old male patient with major depressive disorder for the last 6 months. The patient had been diagnosed with dyslexia during childhood and was left-handed. The intervention protocol consisted in 10 consecutive daily transcranial direct current stimulation sessions. However, after 5 days of stimulation, the patient presented with intensification of depressive symptoms and panic attacks. It was hypothetized that the intensification of symptoms may have been due to stimulation protocol itself. Considering the patient was left-handed and presented comorbidity with dyslexia, there was a plausible hypothesis of right hemispheric dominance. This was corroborated by the Edinburgh Handedness Scale. In fact, dyslexic patients present right hemisphere dominance more frequently. The patient also presented a single photon emission computed tomography with a hypoperfusion area over the left posterior parietal lobe. After the patients agreement, a 10-day experimental repetitive transcranial magnetic stimulation low-frequency protocol over the left dorsolateral prefrontal cortex was started to inhibit the area, which was hypothetically hyperactivated following the rationale of right dominance. The patient presented amelioration of depressive and anxious symptoms. Given the hemispheric reversal we show in the present case study, however, it seems that therapies that are beneficial to right-handers could be detrimental to left-handers.
addition, the right hemisphere mediates vigilance and arousal, which may explain the sleep disturbances often reported in depression. Conversely, the left hemisphere is specifically involved in processing pleasurable experiences, and its relative attenuation is in line with the symptoms of anhedonia that characterize depression. The left hemisphere is also relatively more involved in decision-making processes, accounting for the indecisiveness that is often accompanied with depression.9 We report the case of a 66-year-old male patient with MDD for the last 6 months. The patient had been diagnosed with dyslexia during childhood and was left-handed. Despite previous treatment with venlafaxine (150 mg daily for 2 months) without clinical improvement, the patient was not under any further pharmacological trial due to the fear of possible adverse effects. Considering the availability of tDCS device in our center and patient's accordance, the medical team decided that the patient should undergo an open-label tDCS protocol for major depression after a written informed consent was provided in accordance to Institutional Review Board requirements. The intervention protocol consisted in 10 consecutive daily tDCS sessions was performed including the weekend. The
Key Words: dyslexia, depression, hemispheric dominance (J ECT 2015;31: 201–202)
P
refrontal brain regions, in particular the right and left dorsolateral prefrontal cortex (DLPFC), have been a focus of imaging studies in major depressive disorder (MDD). Using positron emission tomography, resting-state studies revealed reduced cerebral blood flow and metabolism in the left DLPFC and hypermetabolism in the right DLPFC in acute MDD.1,2 The difference between the left and right DLPFC functional state is also reflected in the therapeutic effects of repetitive transcranial magnetic stimulation (rTMS). Patients with MDD benefit from clinical effects of different neuromodulation strategies such as rTMS and transcranial direct current stimulation (tDCS) (ie, increasing or suppressing cortical activity over the DLPFC).3–5 Both positron emission tomography and rTMS findings have led to the imbalance hypothesis of MDD, which postulates prefrontal asymmetry with relative hypoactivity in the left DLPFC and relative hyperactivity in the right DLPFC (Fig. 1).6–8 There is evidence that the right hemisphere is selectively involved in processing negative emotions, pessimistic thoughts, and unconstructive thinking, which in turn might contribute to elevated anxiety, stress, and pain associated with depression. In From the The Clinical Neuromodulation Laboratory, Santa Casa Medical School, São Paulo, Brazil. Received for publication May 2, 2014; accepted July 29, 2014. Reprints: Pedro Shiozawa, MD, Department of Psychiatry, Santa Casa Medical School, Rua Major Maragliano, 241, Vila Mariana, São Paulo 0460001, Brazil (e‐mail: [email protected]). The authors have no conflicts of interest or financial disclosures to report. Copyright © 2014 Wolters Kluwer Health, Inc. All rights reserved. DOI: 10.1097/YCT.0000000000000180
FIGURE 1. Single photon emission computed tomography showing hypoperfusion area located at the left posterior parietal lobe (white circle). Dyslexic patients have reduced activity in cortical areas in the temporoparietal lobe on the left side of the brain (reviewed in Habib14).
Journal of ECT • Volume 31, Number 3, September 2015
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of tDCS on corticospinal excitability differ moderately in the left-handed and mixed-handed population compared with righthanded subjects.15 In clinical scenario, neuromodulation protocols have widely been based on the assumption that the left hemisphere mediates approach motivational states. Given the hemispheric reversal we show in the present case study, however, it seems that therapies that are beneficial to right-handers could be detrimental to lefthanders. In conclusion, the issue of hemispheric dominance should be in focus among research groups when defining interventional protocols as to optimize clinical results. REFERENCES FIGURE 2. Depression and Anxiety scores during intervention protocols as assessed by Hamilton Depression Rating Scale and Beck Anxiety Inventory.
cathode was positioned over the right and the anode over the left DLPFC. We used a direct current of 2.0 mA for 20 minutes each session. The 35-cm2 rubber electrodes were wrapped in cotton material, which was moistened with saline as to reduce impedance. However, after 5 days of stimulation, the patient presented with intensification of depressive symptoms and panic attacks. The experimental protocol was interrupted. It was hypothesized that the intensification of symptoms may have been due to stimulation protocol itself. Considering that the patient was left-handed and presented comorbidity with dyslexia, there was a plausible hypothesis of right hemispheric dominance. This was in fact corroborated by the Edinburgh Handedness Scale (laterality index, −100). In fact, dyslexic patients present right hemisphere dominance more frequently. The patient also presented a single photon emission computed tomography with a hypoperfusion area over the left posterior parietal lobe. Patients with dyslexia present usually with a right hemisphere dominance and have been under an increased risk of presenting comorbidity with MDD.10,11 After patients agreement, a 10-day experimental rTMS lowfrequency protocol over the left DLPFC was commenced as to inhibit this area, which was hypothetically hyperactive following the rationale of right dominance. Stimulation protocol was as follows: 1 Hz stimulation at 90% of motor threshold, with train duration of 60 seconds and session duration of 20 minutes. The rTMS study protocol was performed after we obtained an Institutional Review Board-approved informed consent regarding the new intervention. The patient presented amelioration of depressive and anxiety symptoms as assessed by the Hamilton Depression Rating Scale version 17 items and the Beck Anxiety Inventory (Fig. 2). Many cognitive functions show some degree of variation with handedness. Aspects of language and spatial cognition that are clearly lateralized in right-handers are more bilaterally distributed in left-handers.12–14 To decrease symptoms of depression, neuromodulation strategies such as TMS and tDCS are used to shift the balance of neural activity toward patients' left hemispheres to stimulate approach-related emotions.13 However, a recent controlled trial demonstrated that the modulating effects
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1. Phillips ML, Drevets WC, Rauch SL, et al. Neurobiology of emotion perception II: Implications for major psychiatric disorders. Biol Psychiatry. 2003;54:515–528. 2. Mayberg HS. Modulating dysfunctional limbic-cortical circuits in depression: towards development of brain-based algorithms for diagnosis and optimised treatment. Br Med Bull. 2003;65:193–207. 3. Burt T, Lisanby SH, Sackeim HA. Neuropsychiatric applications of transcranial magnetic stimulation: a meta analysis. Int J Neuropsychopharmacol. 2002;5:73–103. 4. Gershon AA, Dannon PN, Grunhaus L. Transcranial magnetic stimulation in the treatment of depression. Am J Psychiatry. 2003;160: 835–845. 5. Fitzgerald PB, Brown TL, Marston NAU, et al. Transcranial magnetic stimulation in the treatment of depression: a double-blind, placebo-controlled trial. Arch Gen Psychiatry. 2003;60:1002–1008. 6. Sackeim HA, Greenberg MS, Weiman AL, et al. Hemispheric asymmetry in the expression of positive and negative emotions. Neurologic evidence. Arch Neurol. 1982;39:218. 7. Maeda F, Keenan JP, Pascual-Leone A. Interhemispheric asymmetry of motor cortical excitability in major depression as measured by transcranial magnetic stimulation. Br J Psychiatry. 2000;177:169–173. 8. Davidson RJ, Irwin W. The functional neuroanatomy of emotion and affective style. Trends Cogn Sci. 1999;3:11–21. 9. Hecht D. Depression and the hyperactive right-hemisphere. Neurosci Res. 2010;68:77–87. 10. Finn ES, Shen X, Holahan JM, et al. Disruption of functional networks in dyslexia: a whole-brain, data-driven analysis of connectivity. Biol Psychiatry. 2014;76:397–404. 11. Vlachos F1, Andreou E, Delliou A. Brain hemisphericity and developmental dyslexia. Res Dev Disabil. 2013;34:1536–1540. 12. Pujol J, Deus J, Losilla J, et al. Cerebral lateralization of language in normal left handed people studied by functional MRI. Neurology. 1999;52: 1038–1043. 13. Hellige J, Bloch M, Cowin E, et al. Individual variation in hemispheric asymmetry: multitask study of effects related to handedness and sex. J Exp Psychol Gen. 1994;123:235–256. 14. Habib M. The neurological basis of developmental dyslexia: an overview and working hypothesis. Brain. 2000;123:2373–2399. 15. Schade S, Moliadze V, Paulus W, et al. Modulating neuronal excitability in the motor cortex with tDCS shows moderate hemispheric asymmetry due to subjects' handedness: a pilot study. Restor Neurol Neurosci. 2012;30: 191–198.
© 2014 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Transcranial Direct Current Stimulation for Treating Depression in a Patient With Right Hemispheric Dominance A Case Study Pedro Shiozawa, MD, Mailu Enokibara da Silva, MD, and Quirino Cordeiro, MD, PhD Abstract: We report the case of a 66-year-old male patient with major depressive disorder for the last 6 months. The patient had been diagnosed with dyslexia during childhood and was left-handed. The intervention protocol consisted in 10 consecutive daily transcranial direct current stimulation sessions. However, after 5 days of stimulation, the patient presented with intensification of depressive symptoms and panic attacks. It was hypothetized that the intensification of symptoms may have been due to stimulation protocol itself. Considering the patient was left-handed and presented comorbidity with dyslexia, there was a plausible hypothesis of right hemispheric dominance. This was corroborated by the Edinburgh Handedness Scale. In fact, dyslexic patients present right hemisphere dominance more frequently. The patient also presented a single photon emission computed tomography with a hypoperfusion area over the left posterior parietal lobe. After the patients agreement, a 10-day experimental repetitive transcranial magnetic stimulation low-frequency protocol over the left dorsolateral prefrontal cortex was started to inhibit the area, which was hypothetically hyperactivated following the rationale of right dominance. The patient presented amelioration of depressive and anxious symptoms. Given the hemispheric reversal we show in the present case study, however, it seems that therapies that are beneficial to right-handers could be detrimental to left-handers.
addition, the right hemisphere mediates vigilance and arousal, which may explain the sleep disturbances often reported in depression. Conversely, the left hemisphere is specifically involved in processing pleasurable experiences, and its relative attenuation is in line with the symptoms of anhedonia that characterize depression. The left hemisphere is also relatively more involved in decision-making processes, accounting for the indecisiveness that is often accompanied with depression.9 We report the case of a 66-year-old male patient with MDD for the last 6 months. The patient had been diagnosed with dyslexia during childhood and was left-handed. Despite previous treatment with venlafaxine (150 mg daily for 2 months) without clinical improvement, the patient was not under any further pharmacological trial due to the fear of possible adverse effects. Considering the availability of tDCS device in our center and patient's accordance, the medical team decided that the patient should undergo an open-label tDCS protocol for major depression after a written informed consent was provided in accordance to Institutional Review Board requirements. The intervention protocol consisted in 10 consecutive daily tDCS sessions was performed including the weekend. The
Key Words: dyslexia, depression, hemispheric dominance (J ECT 2015;31: 201–202)
P
refrontal brain regions, in particular the right and left dorsolateral prefrontal cortex (DLPFC), have been a focus of imaging studies in major depressive disorder (MDD). Using positron emission tomography, resting-state studies revealed reduced cerebral blood flow and metabolism in the left DLPFC and hypermetabolism in the right DLPFC in acute MDD.1,2 The difference between the left and right DLPFC functional state is also reflected in the therapeutic effects of repetitive transcranial magnetic stimulation (rTMS). Patients with MDD benefit from clinical effects of different neuromodulation strategies such as rTMS and transcranial direct current stimulation (tDCS) (ie, increasing or suppressing cortical activity over the DLPFC).3–5 Both positron emission tomography and rTMS findings have led to the imbalance hypothesis of MDD, which postulates prefrontal asymmetry with relative hypoactivity in the left DLPFC and relative hyperactivity in the right DLPFC (Fig. 1).6–8 There is evidence that the right hemisphere is selectively involved in processing negative emotions, pessimistic thoughts, and unconstructive thinking, which in turn might contribute to elevated anxiety, stress, and pain associated with depression. In From the The Clinical Neuromodulation Laboratory, Santa Casa Medical School, São Paulo, Brazil. Received for publication May 2, 2014; accepted July 29, 2014. Reprints: Pedro Shiozawa, MD, Department of Psychiatry, Santa Casa Medical School, Rua Major Maragliano, 241, Vila Mariana, São Paulo 0460001, Brazil (e‐mail: [email protected]). The authors have no conflicts of interest or financial disclosures to report. Copyright © 2014 Wolters Kluwer Health, Inc. All rights reserved. DOI: 10.1097/YCT.0000000000000180
FIGURE 1. Single photon emission computed tomography showing hypoperfusion area located at the left posterior parietal lobe (white circle). Dyslexic patients have reduced activity in cortical areas in the temporoparietal lobe on the left side of the brain (reviewed in Habib14).
Journal of ECT • Volume 31, Number 3, September 2015
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
www.ectjournal.com
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Journal of ECT • Volume 31, Number 3, September 2015
Shiozawa et al
of tDCS on corticospinal excitability differ moderately in the left-handed and mixed-handed population compared with righthanded subjects.15 In clinical scenario, neuromodulation protocols have widely been based on the assumption that the left hemisphere mediates approach motivational states. Given the hemispheric reversal we show in the present case study, however, it seems that therapies that are beneficial to right-handers could be detrimental to lefthanders. In conclusion, the issue of hemispheric dominance should be in focus among research groups when defining interventional protocols as to optimize clinical results. REFERENCES FIGURE 2. Depression and Anxiety scores during intervention protocols as assessed by Hamilton Depression Rating Scale and Beck Anxiety Inventory.
cathode was positioned over the right and the anode over the left DLPFC. We used a direct current of 2.0 mA for 20 minutes each session. The 35-cm2 rubber electrodes were wrapped in cotton material, which was moistened with saline as to reduce impedance. However, after 5 days of stimulation, the patient presented with intensification of depressive symptoms and panic attacks. The experimental protocol was interrupted. It was hypothesized that the intensification of symptoms may have been due to stimulation protocol itself. Considering that the patient was left-handed and presented comorbidity with dyslexia, there was a plausible hypothesis of right hemispheric dominance. This was in fact corroborated by the Edinburgh Handedness Scale (laterality index, −100). In fact, dyslexic patients present right hemisphere dominance more frequently. The patient also presented a single photon emission computed tomography with a hypoperfusion area over the left posterior parietal lobe. Patients with dyslexia present usually with a right hemisphere dominance and have been under an increased risk of presenting comorbidity with MDD.10,11 After patients agreement, a 10-day experimental rTMS lowfrequency protocol over the left DLPFC was commenced as to inhibit this area, which was hypothetically hyperactive following the rationale of right dominance. Stimulation protocol was as follows: 1 Hz stimulation at 90% of motor threshold, with train duration of 60 seconds and session duration of 20 minutes. The rTMS study protocol was performed after we obtained an Institutional Review Board-approved informed consent regarding the new intervention. The patient presented amelioration of depressive and anxiety symptoms as assessed by the Hamilton Depression Rating Scale version 17 items and the Beck Anxiety Inventory (Fig. 2). Many cognitive functions show some degree of variation with handedness. Aspects of language and spatial cognition that are clearly lateralized in right-handers are more bilaterally distributed in left-handers.12–14 To decrease symptoms of depression, neuromodulation strategies such as TMS and tDCS are used to shift the balance of neural activity toward patients' left hemispheres to stimulate approach-related emotions.13 However, a recent controlled trial demonstrated that the modulating effects
202
www.ectjournal.com
1. Phillips ML, Drevets WC, Rauch SL, et al. Neurobiology of emotion perception II: Implications for major psychiatric disorders. Biol Psychiatry. 2003;54:515–528. 2. Mayberg HS. Modulating dysfunctional limbic-cortical circuits in depression: towards development of brain-based algorithms for diagnosis and optimised treatment. Br Med Bull. 2003;65:193–207. 3. Burt T, Lisanby SH, Sackeim HA. Neuropsychiatric applications of transcranial magnetic stimulation: a meta analysis. Int J Neuropsychopharmacol. 2002;5:73–103. 4. Gershon AA, Dannon PN, Grunhaus L. Transcranial magnetic stimulation in the treatment of depression. Am J Psychiatry. 2003;160: 835–845. 5. Fitzgerald PB, Brown TL, Marston NAU, et al. Transcranial magnetic stimulation in the treatment of depression: a double-blind, placebo-controlled trial. Arch Gen Psychiatry. 2003;60:1002–1008. 6. Sackeim HA, Greenberg MS, Weiman AL, et al. Hemispheric asymmetry in the expression of positive and negative emotions. Neurologic evidence. Arch Neurol. 1982;39:218. 7. Maeda F, Keenan JP, Pascual-Leone A. Interhemispheric asymmetry of motor cortical excitability in major depression as measured by transcranial magnetic stimulation. Br J Psychiatry. 2000;177:169–173. 8. Davidson RJ, Irwin W. The functional neuroanatomy of emotion and affective style. Trends Cogn Sci. 1999;3:11–21. 9. Hecht D. Depression and the hyperactive right-hemisphere. Neurosci Res. 2010;68:77–87. 10. Finn ES, Shen X, Holahan JM, et al. Disruption of functional networks in dyslexia: a whole-brain, data-driven analysis of connectivity. Biol Psychiatry. 2014;76:397–404. 11. Vlachos F1, Andreou E, Delliou A. Brain hemisphericity and developmental dyslexia. Res Dev Disabil. 2013;34:1536–1540. 12. Pujol J, Deus J, Losilla J, et al. Cerebral lateralization of language in normal left handed people studied by functional MRI. Neurology. 1999;52: 1038–1043. 13. Hellige J, Bloch M, Cowin E, et al. Individual variation in hemispheric asymmetry: multitask study of effects related to handedness and sex. J Exp Psychol Gen. 1994;123:235–256. 14. Habib M. The neurological basis of developmental dyslexia: an overview and working hypothesis. Brain. 2000;123:2373–2399. 15. Schade S, Moliadze V, Paulus W, et al. Modulating neuronal excitability in the motor cortex with tDCS shows moderate hemispheric asymmetry due to subjects' handedness: a pilot study. Restor Neurol Neurosci. 2012;30: 191–198.
© 2014 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
