- Email: [email protected]
Exploring resting state connectivity in ECT patients with psychotic depression
Abstracts / Brain Stimulation 10 (2017) 346e540
Introduction: It may be possible to simplify determinants of variability into two groups: intrinsic and extrinsic. Intrinsic variability may relate to factors that are impossible to modify, such as age, gender, and genetics. Extrinsic variability is potentially controllable and includes factors such as detection of the motor hotspot, stability of holding coil, the attention level of subjects in a long experiment, etc. In case of stroke patients, two factors may be added to this extrinsic variability, such as anatomical regions and the time from stroke onset. Methods: Non-invasive brain imaging (fMRI, M/EEG) is increasingly available to determine the underlying residual functional anatomy that will influence the effects of NIBS. Results: Longitudinal imaging studies revealed that different motor related areas were activated in a simple motor task during the course of motor recovery. Discussion: This evidence indicates that brain areas dynamically changes its activation pattern and thus it is necessary to take into account when we use NIBS as an intervention for motor recovery. Keywords: Stroke [0203] EARLY AND LATE ONSET DEPRESSION IN LATE LIFE: A PROSPECTIVE STUDY ON CLINICAL AND STRUCTURAL BRAIN CHARACTERISTICS AND RESPONSE TO ELECTROCONVULSIVE THERAPY A. Dols*1, F. Boeckaert 2, P. Sienaert 2, D. Rhebergen 1, H.C. Comijs 1, M. Oudega 1, E. van Exel 1, M. Vandenbulcke 2, M.L. Stek 1. 1 VU University Medical Center Amsterdam, The Netherlands; 2 University Psychiatric Center KU Leuven, Belgium Introduction: The clinical profile of late life depression is frequently associated with cognitive impairment, aging-related brain changes and somatic comorbidity. This two-site naturalistic longitudinal study aimed to explore differences in clinical and brain characteristics and response to electroconvulsive therapy (ECT) in early (EOD) versus late onset (LOD) late life depression (respectively onset < and 55 years). Methods: Between January 2011 and December 2013, 110 patients aged 55 years and older with ECT treated unipolar depression were included in The Mood Disorders in Elderly treated with ECT study (MODECT). Clinical profile and somatic health were assessed. MRI scans were performed before the first ECT and visually rated. Results: Response rate was 78.2%, and similar between the two sites, but significantly higher in LOD compared to EOD (86.9 vs. 67.3%). Clinical, somatic and brain characteristics were not different between EOD and LOD. Response to ECT was associated with late age at onset and presence of psychotic symptoms, and not with structural MRI characteristics. In EOD only, the odds for a higher response were associated with a shorter index episode. Discussion: The clinical profile, somatic comorbidities and brain characteristics in LLD were similar in EOD and LOD. Nevertheless, patients with LOD showed a superior response to ECT compared to patients with EOD. Our results indicate that ECT is very effective in LLD, even in vascular burdened patients. Keywords: ECT, Late onset depression, response, cliical and structural brain chracteristics [0204] NEW INSIGHTS IN VIVO INTO THE TREATMENT OF MIGRAINE AND OTHER CHRONIC PAIN DISORDERS USING NON-INVASIVE NEUROMODULATION A. DaSilva*. Headache & Orofacial Pain Laboratory, University of Michigan, USA Introduction: While understanding brain mechanisms in chronic pain is important, equally important is applying these concepts in the clinical environment. The advent of neuroimaging has allowed for the identification of an intricate network of brain structures that contributes to the pain experience and their specific roles in each dimension of the whole phenomenon. For example, recent in vivo molecular imaging studies have demonstrated that there is a dysfunctional m-opioid and dopamine D2/D3 neurotransmission in certain brain regions of migraineurs during
387
spontaneous headache attacks and allodynia. Interestingly, several studies with primary motor cortex (M1) stimulation (MCS) have shown that epidural electrodes in M1 are effective in providing analgesia in patients with central pain, and that it occurs via indirect modulation of thalamic activity. Evidently, the invasive nature of such a procedure limits its indication to highly severe pain disorders. Methods: Migraine, chronic pain patients and healthy subjects were scanned using positron emission tomography and magnetic resonance imaging (e.g., MRS, functional connectivity) during clinical and experimental pain, as well as following acute or repetitive neuromodulatory sessions. Results: Our studies have shown scientific evidence that novel noninvasive neuromodulation tools can change endogenous m-opioid neurotransmission, functional connectivity, excitatory and inhibitory brain metabolites, and also provide relatively lasting pain relief in some pain disorders, including chronic migraine, trigeminal neuropathic pain, TMD and fibromyalgia. However, their acute and long-term impact on the central nervous system functioning has not been completely established. Discussion: The overall goal of this session is to discuss novel information in central mechanisms of neuromodulation, especially conventional and high-definition transcranial direct current stimulation (tDCS), and transcranial magnetic stimulation (TMS) for migraine and other chronic pain disorders, their placebo and active effects, neuroanatomical targets (e.g., M1, dorsolateral prefrontal cortex, and visual cortex), as well as neuronal predictors of clinical success and failure. Keywords: Migraine, Pain, Neuroimaging, Neuromodulation [0206] MODELING-INFORMED TACS ALLOWS SHAPING OSCILLATORY ACTIVITY IN SPECIFIC BRAIN NETWORKS C.S. Herrmann*. Oldenburg University, Germany Transcranial alternating current stimulation (tACS) is capable of modulating ongoing brain oscillations and, in turn, cognitive processes. In order to achieve these goals, however, careful planning of the experiment is required. We have used finite element models (FEMs) in order to predict where in the brain tACS will result in enhanced current densities. In addition, we have applied a spiking neural network model to predict the response of brain oscillations to external stimulation. By using electroencephalography (EEG) and magnetoencephalography (MEG), we were able to demonstrate that tACS enhances the amplitude of the human alpha rhythm. This step requires careful consideration of the artefact which is introduced by tACS. With the help of functional magnetic resonance imaging, we could where in the brain tACS interacts with hemodynamic brain responses. We will introduce the methods used and will show cognitive results from visual perception and memory tasks. Keywords: Finite element model, spiking network simulation, cognitive processes, EEG [0207] EXPLORING RESTING STATE CONNECTIVITY IN ECT PATIENTS WITH PSYCHOTIC DEPRESSION M. Oudega*1, Y.D. van der Werf 1, A. Dols 1, F. Boeckaert 2, M. Vandenbulcke 2, P. Sienaert 2, M.L. Stek 1, D. Rhebergen 1, O.A. van den Heuvel 1, E. van Exel 1. 1 VU University Medical Center Amsterdam, The Netherlands; 2 University Psychiatric Center KU Leuven, Belgium Introduction: Severe depression with or without psychotic symptoms is associated with high morbidity and mortality. Network dysfunction may be involved in the disease mechanisms of severe depression. We aim to evaluate network connectivity in severely depressed in-patients with and without psychotic symptoms to gain more insight into the underlying disease mechanisms. Moreover psychotic symptoms show high response to ECT and networks involved in psychotic depression may be involved in the therapeutic mechanism of ECT. Methods: A naturalistic cohort study was performed at two sites. Older patients with major depressive disorder referred for ECT with or without psychotic symptoms were included (n¼23 at site one, n¼26 at site two). Resting state 3-Tesla functional MRI scans, with eyes closed, were obtained and Montgomery-Åsberg Depression Rating Scales were completed. We
388
Abstracts / Brain Stimulation 10 (2017) 346e540
denoised data and calculated resting state networks in the two groups separately. We selected five networks of interest (1.bilateral-, 2.left- and 3.right frontoparietal network, 4.default mode network (DMN) and 5.bilateral basal ganglia and insula network) and performed regression analyses with severity of depression, as well as presence or non-presence of psychotic symptoms. Results: The functional connectivity (FC) pattern did not correlate with severity of depression. Depressed patients with psychotic symptoms (n¼14, 61%) compared with patients without psychotic symptoms (n¼9, 39%) from site one showed significantly decreased FC in the right part of the bilateral frontoparietal network (p¼0.002). This result was not replicated when comparing patients with (n¼9, 35%) and without (n¼17, 65%) psychotic symptoms from site two. Discussion: Psychotic depression may be associated with decreased FC of the frontoparietal network, which is involved in cognitive control processes, such as attention and emotion regulation. These findings suggest that FC in the frontoparietal network may be related to subtype of depression, i.e. presence of psychotic symptoms, rather than severity of depression. Since the findings could not be replicated in the 2nd sample, replication is needed before drawing definite conclusions. Keywords: ECT, resting state connectivity, psychotic depression [0208] GENOME-WIDE META-ANALYSIS OF DNA METHYLATION CHANGES ASSOCIATED WITH ANTIDEPRESSANT EFFECTS OF ELECTROCONVULSIVE THERAPY E. Pishva 1, 2, G. Kenis 1, E. Hannon 1, W. Viechtbauer 1, A. Jeffries 2, R. P. Sienaert 3, J. van Os 1, M.L. Stek 4, B.P.F. Lardenoije 1, Rutten*1. 1 Maastricht University Medical Centre, The Netherlands; 2 3 University of Exeter, UK; University Psychiatric Center KU Leuven, Belgium; 4 VU University Medical Center Amsterdam, The Netherlands Introduction: Electroconvulsive therapy (ECT) is a highly effective treatment, and is most frequently used for patients with treatment-resistant depression. Although it has been proposed that ECT induces alterations in the epigenome, and that these epigenomic alterations may act as a molecular mediator of the antidepressant effects of ECT, no epigenetic studies have been conducted on ECT in humans to date. Methods: Two prospectively followed, independent groups of patients treated with ECT, 12 from Maastricht University Medical Centre (Sample I), and 30 from GGZinGeest, Amsterdam (Sample II), were assessed for longitudinal changes of DNA methylation levels in peripheral blood samples before and one week following the last ECT. at the end of the period of ECT. The Infinium HumanMethylation450 BeadChip was used for measuring the levels of DNA methylation in a genome-wide manner. The MontgomeryeÅsberg Depression Rating Scale (MADRS) was administered before the first ECT treatment (baseline), and each week during the ECT course. A meta-analysis of the two datasets was performed, in order to identify CpG sites showing genome-wide, significant associations between changes in DNA methylation levels and improvement in clinical symptoms of depression across the period of ECT. Gene ontology and pathway analyses were subsequently employed in order to identify the related biological processes and functionally defined pathways for the genes that have been assigned to the top-ranked determined CpG sites. Results: Patients showed significant improvement in depressive symptomatology after ECT. The meta-analysis identified that 2 CpG sites in DNASE1L2 and 1 CpG site in RAD52 passed the highly conservative Bonferroni correction for genome-wide analyses, and that a total of 7 CpG sites in/near the genes DNASE1L2, RAD52, IKBKB and CHST8 passed the false discovery rate threshold of statistical significance. Discussion: This first study on longitudinal changes of DNA methylation and changes in depression score across the period of ECT has provided the first molecular evidence that DNA methylation may contribute to the mechanism of action of ECT. The study identified DNASE1L2, RAD52, IKBKB and CHST8 as candidate genes underlying the antidepressant effect of ECT. Keywords: ECT, Genome-wide meta analysis, DNA methylation changes
[0209] HOME-BASED NEUROMODULATORY TECHNOLOGIES FOR MIGRAINE AND OROFACIAL PAIN DISORDERS A. DaSilva*. University of Michigan, USA Introduction: Migraine is a debilitating chronic condition that affects most of the patient’s life, from childhood to late adulthood. Unfortunately, current medicinal and non-pharmacological treatments for migraine are quite often inadequate for successfully preventing and aborting the attacks that go beyond the headache, including aura, nausea, vomiting and inhibitory behavior. Neuromodulation is a promising, novel approach for the treatment of migraine, other primary headaches and orofacial pain disorders. It offers a new option in the treatment that is easily reversible, tends to be highly tolerated by the patients, and allows for their combination with drug therapies. Mechanisms: There is also growing scientific evidence from neuroimaging studies that neuromodulation has the ability to change endogenous central mechanisms related to migraine suffering, pain perception and persistence, including the mu-opioid system. The positive outcome will depend on several factors, for instance the brain target(s), electric current level used, and also number of sessions. Results: For prophylactic treatment of primary headaches and facial pain disorders, frequent visits to a clinic or hospital for the neuromodulatory sessions are needed to produce meaningful pain relief, which makes the treatment regimen a burdensome for patients; especially when they are incapacitated by their ongoing pain and attacks. Hence, their application in clinical practice will depend on the recent industry's capacity to develop portable and more user-friendly devices. Discussion: This presentation will focus on the most recent advances in home-therapy based neuromodulation for migraine and orofacial pain disorders, including transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), vagus nerve stimulation, transcutaneous supraorbital stimulation, and so forth. In addition, we will discuss current and future suitable platforms for home use, their feasibility, evidence from most recent clinical trials, and potential neuromechanisms for their therapeutic effects. Keywords: Pain, Migraine, Neuroimaging, Home therapy [0210] MAGNETIC FOCUSING BY MAGNETIC SHIELDING FOR NON-INVASIVE BRAIN STIMULATION Q. Meng 1, 2, M. Cherry 1, X. Du 1, H. Lu 2, E. Hong 1, Y. Yang 2, F.-S. Choa*1. 1 University of Maryland, USA; 2 National Institutes of Health, USA Instruction: Transcranial magnetic stimulation (TMS) is one of the most widely used methods for brain stimulation. It is utilized in diagnosis and treatment for many neural diseases, such as neuropathic pain and loss of function caused by stroke. Current commercial TMS stimulators cannot provide well targeted stimulation. Due to fast field divergence, the effective distance in TMS is limited to around 1.5 cm. A breakthrough is needed to achieve non-invasive, focused brain stimulation. Methods: We demonstrated using magnetic shield to achieve magnetic focusing without sacrificing significant amount of throughput. The shield is composed of multiple layers of copper ring arrays, which utilize induced current in the ring to generate counter magnetic fields. We experimentally set up a two pole stimulator system designed for animals (rats). A transient magnetic field probe was used for field measurements. Results: The shield effect depends on not only the design of shield structure but also the intensity of original magnetic field from the stimulator. A higher original magnetic field can produce stronger counter field and achieve smaller size focal point. A tight focal spot with a diameter of 0.5cm was achieved by using 4 layers of copper ring arrays when data was measured at mid plane of the stimulator and 3cm away from iron surface as figure 1a illustrated. Discussion: With proper designing and arrangement of array structures and rings locations, the combined original and counter fields can produce a final focused field distribution. Such a multilayer copper ring array made shield structure will be useful for future targeted non-invasive stimulation applications.
Introduction: It may be possible to simplify determinants of variability into two groups: intrinsic and extrinsic. Intrinsic variability may relate to factors that are impossible to modify, such as age, gender, and genetics. Extrinsic variability is potentially controllable and includes factors such as detection of the motor hotspot, stability of holding coil, the attention level of subjects in a long experiment, etc. In case of stroke patients, two factors may be added to this extrinsic variability, such as anatomical regions and the time from stroke onset. Methods: Non-invasive brain imaging (fMRI, M/EEG) is increasingly available to determine the underlying residual functional anatomy that will influence the effects of NIBS. Results: Longitudinal imaging studies revealed that different motor related areas were activated in a simple motor task during the course of motor recovery. Discussion: This evidence indicates that brain areas dynamically changes its activation pattern and thus it is necessary to take into account when we use NIBS as an intervention for motor recovery. Keywords: Stroke [0203] EARLY AND LATE ONSET DEPRESSION IN LATE LIFE: A PROSPECTIVE STUDY ON CLINICAL AND STRUCTURAL BRAIN CHARACTERISTICS AND RESPONSE TO ELECTROCONVULSIVE THERAPY A. Dols*1, F. Boeckaert 2, P. Sienaert 2, D. Rhebergen 1, H.C. Comijs 1, M. Oudega 1, E. van Exel 1, M. Vandenbulcke 2, M.L. Stek 1. 1 VU University Medical Center Amsterdam, The Netherlands; 2 University Psychiatric Center KU Leuven, Belgium Introduction: The clinical profile of late life depression is frequently associated with cognitive impairment, aging-related brain changes and somatic comorbidity. This two-site naturalistic longitudinal study aimed to explore differences in clinical and brain characteristics and response to electroconvulsive therapy (ECT) in early (EOD) versus late onset (LOD) late life depression (respectively onset < and 55 years). Methods: Between January 2011 and December 2013, 110 patients aged 55 years and older with ECT treated unipolar depression were included in The Mood Disorders in Elderly treated with ECT study (MODECT). Clinical profile and somatic health were assessed. MRI scans were performed before the first ECT and visually rated. Results: Response rate was 78.2%, and similar between the two sites, but significantly higher in LOD compared to EOD (86.9 vs. 67.3%). Clinical, somatic and brain characteristics were not different between EOD and LOD. Response to ECT was associated with late age at onset and presence of psychotic symptoms, and not with structural MRI characteristics. In EOD only, the odds for a higher response were associated with a shorter index episode. Discussion: The clinical profile, somatic comorbidities and brain characteristics in LLD were similar in EOD and LOD. Nevertheless, patients with LOD showed a superior response to ECT compared to patients with EOD. Our results indicate that ECT is very effective in LLD, even in vascular burdened patients. Keywords: ECT, Late onset depression, response, cliical and structural brain chracteristics [0204] NEW INSIGHTS IN VIVO INTO THE TREATMENT OF MIGRAINE AND OTHER CHRONIC PAIN DISORDERS USING NON-INVASIVE NEUROMODULATION A. DaSilva*. Headache & Orofacial Pain Laboratory, University of Michigan, USA Introduction: While understanding brain mechanisms in chronic pain is important, equally important is applying these concepts in the clinical environment. The advent of neuroimaging has allowed for the identification of an intricate network of brain structures that contributes to the pain experience and their specific roles in each dimension of the whole phenomenon. For example, recent in vivo molecular imaging studies have demonstrated that there is a dysfunctional m-opioid and dopamine D2/D3 neurotransmission in certain brain regions of migraineurs during
387
spontaneous headache attacks and allodynia. Interestingly, several studies with primary motor cortex (M1) stimulation (MCS) have shown that epidural electrodes in M1 are effective in providing analgesia in patients with central pain, and that it occurs via indirect modulation of thalamic activity. Evidently, the invasive nature of such a procedure limits its indication to highly severe pain disorders. Methods: Migraine, chronic pain patients and healthy subjects were scanned using positron emission tomography and magnetic resonance imaging (e.g., MRS, functional connectivity) during clinical and experimental pain, as well as following acute or repetitive neuromodulatory sessions. Results: Our studies have shown scientific evidence that novel noninvasive neuromodulation tools can change endogenous m-opioid neurotransmission, functional connectivity, excitatory and inhibitory brain metabolites, and also provide relatively lasting pain relief in some pain disorders, including chronic migraine, trigeminal neuropathic pain, TMD and fibromyalgia. However, their acute and long-term impact on the central nervous system functioning has not been completely established. Discussion: The overall goal of this session is to discuss novel information in central mechanisms of neuromodulation, especially conventional and high-definition transcranial direct current stimulation (tDCS), and transcranial magnetic stimulation (TMS) for migraine and other chronic pain disorders, their placebo and active effects, neuroanatomical targets (e.g., M1, dorsolateral prefrontal cortex, and visual cortex), as well as neuronal predictors of clinical success and failure. Keywords: Migraine, Pain, Neuroimaging, Neuromodulation [0206] MODELING-INFORMED TACS ALLOWS SHAPING OSCILLATORY ACTIVITY IN SPECIFIC BRAIN NETWORKS C.S. Herrmann*. Oldenburg University, Germany Transcranial alternating current stimulation (tACS) is capable of modulating ongoing brain oscillations and, in turn, cognitive processes. In order to achieve these goals, however, careful planning of the experiment is required. We have used finite element models (FEMs) in order to predict where in the brain tACS will result in enhanced current densities. In addition, we have applied a spiking neural network model to predict the response of brain oscillations to external stimulation. By using electroencephalography (EEG) and magnetoencephalography (MEG), we were able to demonstrate that tACS enhances the amplitude of the human alpha rhythm. This step requires careful consideration of the artefact which is introduced by tACS. With the help of functional magnetic resonance imaging, we could where in the brain tACS interacts with hemodynamic brain responses. We will introduce the methods used and will show cognitive results from visual perception and memory tasks. Keywords: Finite element model, spiking network simulation, cognitive processes, EEG [0207] EXPLORING RESTING STATE CONNECTIVITY IN ECT PATIENTS WITH PSYCHOTIC DEPRESSION M. Oudega*1, Y.D. van der Werf 1, A. Dols 1, F. Boeckaert 2, M. Vandenbulcke 2, P. Sienaert 2, M.L. Stek 1, D. Rhebergen 1, O.A. van den Heuvel 1, E. van Exel 1. 1 VU University Medical Center Amsterdam, The Netherlands; 2 University Psychiatric Center KU Leuven, Belgium Introduction: Severe depression with or without psychotic symptoms is associated with high morbidity and mortality. Network dysfunction may be involved in the disease mechanisms of severe depression. We aim to evaluate network connectivity in severely depressed in-patients with and without psychotic symptoms to gain more insight into the underlying disease mechanisms. Moreover psychotic symptoms show high response to ECT and networks involved in psychotic depression may be involved in the therapeutic mechanism of ECT. Methods: A naturalistic cohort study was performed at two sites. Older patients with major depressive disorder referred for ECT with or without psychotic symptoms were included (n¼23 at site one, n¼26 at site two). Resting state 3-Tesla functional MRI scans, with eyes closed, were obtained and Montgomery-Åsberg Depression Rating Scales were completed. We
388
Abstracts / Brain Stimulation 10 (2017) 346e540
denoised data and calculated resting state networks in the two groups separately. We selected five networks of interest (1.bilateral-, 2.left- and 3.right frontoparietal network, 4.default mode network (DMN) and 5.bilateral basal ganglia and insula network) and performed regression analyses with severity of depression, as well as presence or non-presence of psychotic symptoms. Results: The functional connectivity (FC) pattern did not correlate with severity of depression. Depressed patients with psychotic symptoms (n¼14, 61%) compared with patients without psychotic symptoms (n¼9, 39%) from site one showed significantly decreased FC in the right part of the bilateral frontoparietal network (p¼0.002). This result was not replicated when comparing patients with (n¼9, 35%) and without (n¼17, 65%) psychotic symptoms from site two. Discussion: Psychotic depression may be associated with decreased FC of the frontoparietal network, which is involved in cognitive control processes, such as attention and emotion regulation. These findings suggest that FC in the frontoparietal network may be related to subtype of depression, i.e. presence of psychotic symptoms, rather than severity of depression. Since the findings could not be replicated in the 2nd sample, replication is needed before drawing definite conclusions. Keywords: ECT, resting state connectivity, psychotic depression [0208] GENOME-WIDE META-ANALYSIS OF DNA METHYLATION CHANGES ASSOCIATED WITH ANTIDEPRESSANT EFFECTS OF ELECTROCONVULSIVE THERAPY E. Pishva 1, 2, G. Kenis 1, E. Hannon 1, W. Viechtbauer 1, A. Jeffries 2, R. P. Sienaert 3, J. van Os 1, M.L. Stek 4, B.P.F. Lardenoije 1, Rutten*1. 1 Maastricht University Medical Centre, The Netherlands; 2 3 University of Exeter, UK; University Psychiatric Center KU Leuven, Belgium; 4 VU University Medical Center Amsterdam, The Netherlands Introduction: Electroconvulsive therapy (ECT) is a highly effective treatment, and is most frequently used for patients with treatment-resistant depression. Although it has been proposed that ECT induces alterations in the epigenome, and that these epigenomic alterations may act as a molecular mediator of the antidepressant effects of ECT, no epigenetic studies have been conducted on ECT in humans to date. Methods: Two prospectively followed, independent groups of patients treated with ECT, 12 from Maastricht University Medical Centre (Sample I), and 30 from GGZinGeest, Amsterdam (Sample II), were assessed for longitudinal changes of DNA methylation levels in peripheral blood samples before and one week following the last ECT. at the end of the period of ECT. The Infinium HumanMethylation450 BeadChip was used for measuring the levels of DNA methylation in a genome-wide manner. The MontgomeryeÅsberg Depression Rating Scale (MADRS) was administered before the first ECT treatment (baseline), and each week during the ECT course. A meta-analysis of the two datasets was performed, in order to identify CpG sites showing genome-wide, significant associations between changes in DNA methylation levels and improvement in clinical symptoms of depression across the period of ECT. Gene ontology and pathway analyses were subsequently employed in order to identify the related biological processes and functionally defined pathways for the genes that have been assigned to the top-ranked determined CpG sites. Results: Patients showed significant improvement in depressive symptomatology after ECT. The meta-analysis identified that 2 CpG sites in DNASE1L2 and 1 CpG site in RAD52 passed the highly conservative Bonferroni correction for genome-wide analyses, and that a total of 7 CpG sites in/near the genes DNASE1L2, RAD52, IKBKB and CHST8 passed the false discovery rate threshold of statistical significance. Discussion: This first study on longitudinal changes of DNA methylation and changes in depression score across the period of ECT has provided the first molecular evidence that DNA methylation may contribute to the mechanism of action of ECT. The study identified DNASE1L2, RAD52, IKBKB and CHST8 as candidate genes underlying the antidepressant effect of ECT. Keywords: ECT, Genome-wide meta analysis, DNA methylation changes
[0209] HOME-BASED NEUROMODULATORY TECHNOLOGIES FOR MIGRAINE AND OROFACIAL PAIN DISORDERS A. DaSilva*. University of Michigan, USA Introduction: Migraine is a debilitating chronic condition that affects most of the patient’s life, from childhood to late adulthood. Unfortunately, current medicinal and non-pharmacological treatments for migraine are quite often inadequate for successfully preventing and aborting the attacks that go beyond the headache, including aura, nausea, vomiting and inhibitory behavior. Neuromodulation is a promising, novel approach for the treatment of migraine, other primary headaches and orofacial pain disorders. It offers a new option in the treatment that is easily reversible, tends to be highly tolerated by the patients, and allows for their combination with drug therapies. Mechanisms: There is also growing scientific evidence from neuroimaging studies that neuromodulation has the ability to change endogenous central mechanisms related to migraine suffering, pain perception and persistence, including the mu-opioid system. The positive outcome will depend on several factors, for instance the brain target(s), electric current level used, and also number of sessions. Results: For prophylactic treatment of primary headaches and facial pain disorders, frequent visits to a clinic or hospital for the neuromodulatory sessions are needed to produce meaningful pain relief, which makes the treatment regimen a burdensome for patients; especially when they are incapacitated by their ongoing pain and attacks. Hence, their application in clinical practice will depend on the recent industry's capacity to develop portable and more user-friendly devices. Discussion: This presentation will focus on the most recent advances in home-therapy based neuromodulation for migraine and orofacial pain disorders, including transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), vagus nerve stimulation, transcutaneous supraorbital stimulation, and so forth. In addition, we will discuss current and future suitable platforms for home use, their feasibility, evidence from most recent clinical trials, and potential neuromechanisms for their therapeutic effects. Keywords: Pain, Migraine, Neuroimaging, Home therapy [0210] MAGNETIC FOCUSING BY MAGNETIC SHIELDING FOR NON-INVASIVE BRAIN STIMULATION Q. Meng 1, 2, M. Cherry 1, X. Du 1, H. Lu 2, E. Hong 1, Y. Yang 2, F.-S. Choa*1. 1 University of Maryland, USA; 2 National Institutes of Health, USA Instruction: Transcranial magnetic stimulation (TMS) is one of the most widely used methods for brain stimulation. It is utilized in diagnosis and treatment for many neural diseases, such as neuropathic pain and loss of function caused by stroke. Current commercial TMS stimulators cannot provide well targeted stimulation. Due to fast field divergence, the effective distance in TMS is limited to around 1.5 cm. A breakthrough is needed to achieve non-invasive, focused brain stimulation. Methods: We demonstrated using magnetic shield to achieve magnetic focusing without sacrificing significant amount of throughput. The shield is composed of multiple layers of copper ring arrays, which utilize induced current in the ring to generate counter magnetic fields. We experimentally set up a two pole stimulator system designed for animals (rats). A transient magnetic field probe was used for field measurements. Results: The shield effect depends on not only the design of shield structure but also the intensity of original magnetic field from the stimulator. A higher original magnetic field can produce stronger counter field and achieve smaller size focal point. A tight focal spot with a diameter of 0.5cm was achieved by using 4 layers of copper ring arrays when data was measured at mid plane of the stimulator and 3cm away from iron surface as figure 1a illustrated. Discussion: With proper designing and arrangement of array structures and rings locations, the combined original and counter fields can produce a final focused field distribution. Such a multilayer copper ring array made shield structure will be useful for future targeted non-invasive stimulation applications.