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Temporal neuronavigation of transcranial brain stimulation: Exploiting the periodicity of intrinsic brain activity
398
Abstracts / Brain Stimulation 10 (2017) 346e540
admitted to study was randomly assigned into active treatment (n ¼ 19) or sham (n ¼ 21) group. Patients’ antipsychotic medication was kept unchanged during the study. The patients received 13e15 session of aTMS at 110% motor threshold or sham stimulation over the left dorsolateral prefrontal cortex (DLPFC), as adjunctive therapy, for 3 weeks. The clinical assessments were made with the Positive and Negative Syndrome Scale (PANSS) at baseline and 5 days after treatment. Results: Treatment with individualized a-frequency nTMS for 3 weeks significantly improved general psychotic symptoms in the active aTMS group (p ¼ 0.033, effect size ¼ 0.65). Also, there was a statistically significant difference in total PANSS scores between the two groups (p ¼ 0.035, effect size ¼ 0.63). Positive or negative symptoms showed no significant differences in change between groups. Discussion: Application of aTMS to the left DLPFC was beneficial compared with sham in improving total and general psychopathological symptoms of schizophrenia. These results suggest that aTMS may be an efficient add-on therapy for treatment-resistant schizophrenia. Keywords: Repetitive magnetic stimulation, Alpha rhythm, Schizophrenia, Treatment resistance [0253] PREFRONTAL ANODAL TDCS AS A NEUROPSYCHIATRIC TREATMENT eFACTORS BEYOND PREFRONTAL STIMULATION. C.K. Loo*, D. Martin, K.-A. Ho, A. Alonzo, S. Bai, S. Dokos. University of New South Wales, Australia Introduction: Anodal tDCS to the prefrontal cortex is currently being investigated for treatment of a range of neuropsychiatric disorders, including depression, schizophrenia, anxiety, cognitive impairment. The rationale of treatment has focussed on enhancement of prefrontal function. Methods: Using depression as an example, a series of studies investigated the effectiveness of prefrontal anodal tDCS when the position of the cathode was varied (right prefrontal (n¼100), extracephalic (n¼11), occipital (n¼7), cerebellar (n¼7)). A pilot study also tested tDCS with electrodes placed over bilateral anterior temporal regions, similar to the montage used in bitemporal ECT (n¼4). Using a “platform research” approach, some participants participated in more than 1 study, treated during different episodes of depression. Computational modelling was used to demonstrate electric field distribution patterns with these different montages, based on an anatomically accurate head model reconstructed from MRI head and brain scans of a healthy male. Results: Antidepressant effects were seen with all the above montage arrangements except for fronto-cerebellar tDCS, though computational modelling results showed that all the prefrontal anodal tDCS montages resulted in substantive prefrontal stimulation. Fronto-extracephalic tDCS appeared to result in a faster onset of action. Computational modelling results showed that montages differed in intensity of stimulation in the subgenual anterior cingulate, brainstem, cerebellum and temporal lobe regions, with fronto-extracephalic tDCS resulting in greater stimulation particularly in anterior cingulate and brainstem areas. Discussion: Though small numbers were involved in the pilot studies, the above clinical and modelling data suggest that stimulation of regions other than the prefrontal cortex may be important for the neuropsychiatric effects of tDCS, investigated here in depression. Keywords: prefrontal stimulation, neuropsychiatric disorder, treatment, computer modelling [0256] TEMPORAL NEURONAVIGATION OF TRANSCRANIAL BRAIN STIMULATION: EXPLOITING THE PERIODICITY OF INTRINSIC BRAIN ACTIVITY H.R. Siebner*1, 2. 1 Copenhagen University Hospital Hvidovre, Denmark; Copenhagen University Hospital Bispebjerg, Denmark
2
Purpose: To discuss recent studies that show the feasibility and potential of brain-state informed transcranial brain stimulation (TBS) in the “time domain”. The presentation will focus on TBS approaches in which the timing or pattern of TBS was adjusted to the rhythmicity of the intrinsic neural activity in the targeted brain region (i.e., primary motor hand area).
Methods: In healthy young volunteers, we performed electrophysiological proof-of-principle studies which involved TBS of the human primary motor hand area. We used electroencephalographic or electromyographic recordings to identify rhythmic fluctuations of cortical activity (EEG) or corticomotor excitability (MEP) We realized a “closed-loop” EEG-TMS approach which traced the oscillatory activity on-line and used this information to selectively apply TBS in a specific phase of the ongoing oscillation. Using an “open-loop” approach, we first captured the temporal profile of regionally expressed cortical activity or excitability changes and used this information to design “open-loop” TBS protocols with individually adjusted temporal patterns. Results: The studies provided converging evidence that the responsiveness to TBS is modified by the intrinsic oscillatory properties of the targeted cortex. Conclusions: The temporal pattern of intrinsic brain activity can inform the optimal timing or the selection of the optimal rhythmic pattern of TBS. Once these temporal relationships and the underlying mechanisms are systematically investigated and thoroughly understood, the periodicity of intrinsic brain activity will become a promising target for personalized TBS. Increasing the state-specific, temporal precision of TBS and maximizing temporal resonance between intrinsic and TBS-induced neural activity constitute promising strategies to boost the efficacy and reliability of TBS in a therapeutic setting. Keywords: Closed loop stimulation, Cortical oscillation, Combining EEGTMS, Temporal neuronavigation [0257] CLOSED-LOOP TRANSCRANIAL BRAIN STIMULATION DURING SLEEP: EEG-INFORMED, PHASE-SPECIFIC TARGETING OF HUMAN SLOW OSCILLATIONS WITH SINGLE-PULSE TMS H.R. Siebner*1, 2. 1 Copenhagen University Hospital Hvidovre, Denmark; Copenhagen University Hospital Bispebjerg, Denmark
2
Purpose: To provide proof-of-concept that the phase of oscillatory neocortical activity has a significant impact on the brain response evoked by single-pulse transcranial magnetic stimulation (sp-TMS). Methods: In healthy young volunteers, we traced the expression of slow oscillations (SO) in real time during non-rapid eye movement (NREM) sleep. We used this information to apply sp-TMS during opposite phases of spontaneously expressed SO. SOs consist of alternating phases of global depolarization (up-state) and hyperpolarization (down-state) which are associated with marked fluctuations in spontaneous neuronal excitation. We reasoned that this should be reflected in phase-dependent shifts in neocortical excitability. We tested this hypothesis by applying focal single-pulse TMS to the primary motor cortical hand area (M1HAND). The timing of TMS was determined by a closed-loop set-up: Single TMS pulses were triggered online by automatic detection of SO up-states and down-states in the EEG. Results: We found rapid phase-dependent shifts in neocortical excitability in the human M1-HAND. Both, MEPs and TEPs, were consistently larger when evoked during SO up-states than during down-states. Within each SO state, TEP amplitudes depended on the actual EEG potential at the time and site of stimulation. Conclusions: The EEG-informed, closed-loop EEG-TMS set-up enables temporal neuronavigation of TMS by selectively targeting distinct phases of neocortical oscillations. The increased temporal precision and the possibility to target distinct oscillatory neocortical states in a closed-loop fashion bear great potential for optimizing and individualizing therapeutic TMS interventions. Keywords: Closed-loop stimulation, Cortical oscillation, Sleep, Temporal neuronavigation [0260] INFLUENCE OF HIGH-DEFINITION ANODAL TRANSCRANIAL DIRECT CURRENT STIMULATION (HD-ATDCS) ON MOTOR LEARNING OF A HIGH-SPEED BIMANUAL TASK N.H. Pixa*, F. Steinberg, M. Doppelmayr. Johannes Gutenberg-University Mainz, Germany
Abstracts / Brain Stimulation 10 (2017) 346e540
admitted to study was randomly assigned into active treatment (n ¼ 19) or sham (n ¼ 21) group. Patients’ antipsychotic medication was kept unchanged during the study. The patients received 13e15 session of aTMS at 110% motor threshold or sham stimulation over the left dorsolateral prefrontal cortex (DLPFC), as adjunctive therapy, for 3 weeks. The clinical assessments were made with the Positive and Negative Syndrome Scale (PANSS) at baseline and 5 days after treatment. Results: Treatment with individualized a-frequency nTMS for 3 weeks significantly improved general psychotic symptoms in the active aTMS group (p ¼ 0.033, effect size ¼ 0.65). Also, there was a statistically significant difference in total PANSS scores between the two groups (p ¼ 0.035, effect size ¼ 0.63). Positive or negative symptoms showed no significant differences in change between groups. Discussion: Application of aTMS to the left DLPFC was beneficial compared with sham in improving total and general psychopathological symptoms of schizophrenia. These results suggest that aTMS may be an efficient add-on therapy for treatment-resistant schizophrenia. Keywords: Repetitive magnetic stimulation, Alpha rhythm, Schizophrenia, Treatment resistance [0253] PREFRONTAL ANODAL TDCS AS A NEUROPSYCHIATRIC TREATMENT eFACTORS BEYOND PREFRONTAL STIMULATION. C.K. Loo*, D. Martin, K.-A. Ho, A. Alonzo, S. Bai, S. Dokos. University of New South Wales, Australia Introduction: Anodal tDCS to the prefrontal cortex is currently being investigated for treatment of a range of neuropsychiatric disorders, including depression, schizophrenia, anxiety, cognitive impairment. The rationale of treatment has focussed on enhancement of prefrontal function. Methods: Using depression as an example, a series of studies investigated the effectiveness of prefrontal anodal tDCS when the position of the cathode was varied (right prefrontal (n¼100), extracephalic (n¼11), occipital (n¼7), cerebellar (n¼7)). A pilot study also tested tDCS with electrodes placed over bilateral anterior temporal regions, similar to the montage used in bitemporal ECT (n¼4). Using a “platform research” approach, some participants participated in more than 1 study, treated during different episodes of depression. Computational modelling was used to demonstrate electric field distribution patterns with these different montages, based on an anatomically accurate head model reconstructed from MRI head and brain scans of a healthy male. Results: Antidepressant effects were seen with all the above montage arrangements except for fronto-cerebellar tDCS, though computational modelling results showed that all the prefrontal anodal tDCS montages resulted in substantive prefrontal stimulation. Fronto-extracephalic tDCS appeared to result in a faster onset of action. Computational modelling results showed that montages differed in intensity of stimulation in the subgenual anterior cingulate, brainstem, cerebellum and temporal lobe regions, with fronto-extracephalic tDCS resulting in greater stimulation particularly in anterior cingulate and brainstem areas. Discussion: Though small numbers were involved in the pilot studies, the above clinical and modelling data suggest that stimulation of regions other than the prefrontal cortex may be important for the neuropsychiatric effects of tDCS, investigated here in depression. Keywords: prefrontal stimulation, neuropsychiatric disorder, treatment, computer modelling [0256] TEMPORAL NEURONAVIGATION OF TRANSCRANIAL BRAIN STIMULATION: EXPLOITING THE PERIODICITY OF INTRINSIC BRAIN ACTIVITY H.R. Siebner*1, 2. 1 Copenhagen University Hospital Hvidovre, Denmark; Copenhagen University Hospital Bispebjerg, Denmark
2
Purpose: To discuss recent studies that show the feasibility and potential of brain-state informed transcranial brain stimulation (TBS) in the “time domain”. The presentation will focus on TBS approaches in which the timing or pattern of TBS was adjusted to the rhythmicity of the intrinsic neural activity in the targeted brain region (i.e., primary motor hand area).
Methods: In healthy young volunteers, we performed electrophysiological proof-of-principle studies which involved TBS of the human primary motor hand area. We used electroencephalographic or electromyographic recordings to identify rhythmic fluctuations of cortical activity (EEG) or corticomotor excitability (MEP) We realized a “closed-loop” EEG-TMS approach which traced the oscillatory activity on-line and used this information to selectively apply TBS in a specific phase of the ongoing oscillation. Using an “open-loop” approach, we first captured the temporal profile of regionally expressed cortical activity or excitability changes and used this information to design “open-loop” TBS protocols with individually adjusted temporal patterns. Results: The studies provided converging evidence that the responsiveness to TBS is modified by the intrinsic oscillatory properties of the targeted cortex. Conclusions: The temporal pattern of intrinsic brain activity can inform the optimal timing or the selection of the optimal rhythmic pattern of TBS. Once these temporal relationships and the underlying mechanisms are systematically investigated and thoroughly understood, the periodicity of intrinsic brain activity will become a promising target for personalized TBS. Increasing the state-specific, temporal precision of TBS and maximizing temporal resonance between intrinsic and TBS-induced neural activity constitute promising strategies to boost the efficacy and reliability of TBS in a therapeutic setting. Keywords: Closed loop stimulation, Cortical oscillation, Combining EEGTMS, Temporal neuronavigation [0257] CLOSED-LOOP TRANSCRANIAL BRAIN STIMULATION DURING SLEEP: EEG-INFORMED, PHASE-SPECIFIC TARGETING OF HUMAN SLOW OSCILLATIONS WITH SINGLE-PULSE TMS H.R. Siebner*1, 2. 1 Copenhagen University Hospital Hvidovre, Denmark; Copenhagen University Hospital Bispebjerg, Denmark
2
Purpose: To provide proof-of-concept that the phase of oscillatory neocortical activity has a significant impact on the brain response evoked by single-pulse transcranial magnetic stimulation (sp-TMS). Methods: In healthy young volunteers, we traced the expression of slow oscillations (SO) in real time during non-rapid eye movement (NREM) sleep. We used this information to apply sp-TMS during opposite phases of spontaneously expressed SO. SOs consist of alternating phases of global depolarization (up-state) and hyperpolarization (down-state) which are associated with marked fluctuations in spontaneous neuronal excitation. We reasoned that this should be reflected in phase-dependent shifts in neocortical excitability. We tested this hypothesis by applying focal single-pulse TMS to the primary motor cortical hand area (M1HAND). The timing of TMS was determined by a closed-loop set-up: Single TMS pulses were triggered online by automatic detection of SO up-states and down-states in the EEG. Results: We found rapid phase-dependent shifts in neocortical excitability in the human M1-HAND. Both, MEPs and TEPs, were consistently larger when evoked during SO up-states than during down-states. Within each SO state, TEP amplitudes depended on the actual EEG potential at the time and site of stimulation. Conclusions: The EEG-informed, closed-loop EEG-TMS set-up enables temporal neuronavigation of TMS by selectively targeting distinct phases of neocortical oscillations. The increased temporal precision and the possibility to target distinct oscillatory neocortical states in a closed-loop fashion bear great potential for optimizing and individualizing therapeutic TMS interventions. Keywords: Closed-loop stimulation, Cortical oscillation, Sleep, Temporal neuronavigation [0260] INFLUENCE OF HIGH-DEFINITION ANODAL TRANSCRANIAL DIRECT CURRENT STIMULATION (HD-ATDCS) ON MOTOR LEARNING OF A HIGH-SPEED BIMANUAL TASK N.H. Pixa*, F. Steinberg, M. Doppelmayr. Johannes Gutenberg-University Mainz, Germany