- Email: [email protected]
Effects of electrode drift in transcranial direct current stimulation
320
Abstracts / Brain Stimulation 8 (2015) 310e325
cortical inhibition and facilitation, and silent period) of the stimulated and non-stimulated motor cortex before and after navigated rTMS. rTMS induced a significant increase in excitability in the affected (non-stimulated ) motor cortex (p <0.001) and led to improved performance in the finger tapping task and pinch force task (p < 0.001 and p < 0.002 respectively). These physiological and behavioral effects were more prominent (or robust) in the group of stroke patients than in the control group. Low-frequency rTMS involving precise and consistent targeting of the unaffected hemisphere in stroke patients enhanced the cortical excitability of the affected hemisphere and the motor response of the hemiparetic hand. The effects of rTMS were more robust in patients than in healthy subjects. These findings support that (1) navigated rTMS can improve motor function in stroke, and (2) that pathophysiology following unilateral lesion might positively bias the rTMS response.
45 Contralateral and ipsilateral corticobulbar pathway projections for laryngeal muscles in healthy subjects and patients Marina Zmajevic Schönwald a,*, Maja Rogic Vidakovic b,* a Department of Neurosurgery, Clinical Unit for Intraoperative Neurophysiologic Monitoring, Clinical Medical Centre “Sisters of Mercy”, Zagreb, Croatia b Laboratory for Human and Experimental Neurophysiology (LAHEN), Department of Neuroscience, School of Medicine, University of Split, Croatia, Tel.:+385(0)21 557 876 *E-mail: [email protected], [email protected]. Introduction: Here we present assessment of excitability of contralateral and ipsilateral corticobulbar pathways, using the methodologies of navigated transcranial magnetic stimulation (nTMS) and transcranial electrical stimulation (TES). Methods: In the present study we applied event-related nTMS generating modified patterned nTMS protocol to the primary motor cortex for laryngeal muscle representation of the left and right hemisphere, respectively, and recorded contralateral (left hemisphere stimulation) and ipsilateral (right hemisphere stimulation) corticobulbar motor evoked potentials (CoMEPs) from the right cricothyroid muscle in the group of 11 healthy subjects. In the group of 15 patients under undergoing craniotomy, CoMEPs were recorded from bilateral cricothyroid muscles by applying TES over C3/Cz and C4/Cz. Results: In 5 out of 11 healthy subjects both contralateral and ipsilateral CoMEPs were recorded from right cricothyroid muscle. In 8 out of 15 patients contralateral and ipsilateral CoMEPs were elicited with TES over C3/Cz, while in 5 out of 15 patients contralateral and ipsilateral CoMEPs were elicited with TES over C4/Cz. Contralateral CoMEP amplitude responses were significantly larger compared to ipsilateral CoMEP amplitudes in both groups. Discussions: We obtained significantly larger amplitude responses of contralateral CoMEPs from laryngeal muscles compared to ipsilateral CoMEPs amplitude using nTMS in healthy subjects and TES in patients. This confirms bilateral nature of corticobulbar pathways projections for laryngeal muscles, with contralateral domination. These findings will influence preoperative and intraoperative CoMEPs monitoring and mapping of primary motor cortex for laryngeal muscles, and facilitate neurophysiologic research of motor speech disorders.
46 Transcranial Magnetic Stimulation Neurophysiologic and Therapeutic Studies in Child and Adolescent Depression Paul Croarkin DO, MSCS Assistant Professor of Psychiatry, Mayo Clinic, Rochester, MN, USA
Major Depressive Disorder (MDD) is a common psychiatric disease in childhood which confers substantial morbidity and a significant societal burden. The pathophysiology and optimal treatment of early-onset MDD is poorly understood. Transcranial magnetic stimulation (TMS) is an important tool for therapeutic and neurophysiologic research studies in children and adolescents with mood disorders. This presentation will provide an overview of recent work from the Mayo Clinic Pediatric Neurostimulation lab. Recent neurophysiologic investigations examining youth with MDD and healthy controls include a cross-sectional study of cortical excitability (assessed with motor threshold and intracortical facilitation measures) and inhibition (assessed with shortinterval cortical inhibition and cortical silent period measures). Initial results suggest that children and adolescents with depression have increased glutamatergic intracortical facilitation. Another study examining long-interval cortical inhibition in depressed adolescents initiating treatment with fluoxetine suggests that baseline deficits in long-interval cortical inhibition may be associated with a poor response to fluoxetine. Exploratory work also suggests that motor threshold and long-interval cortical inhibition measures change with age in early life. Our group has now also treated 24 depressed adolescents with high frequency repetitive transcranial magnetic stimulation. (30 sessions of 10 Hz rTMS at 120% motor threshold). In open-label treatment, the mean Children’s Depression Rating Scale Revised score increased over the course of 30 sessions and further at 6 month follow-up. A blinded, randomized, sham-controlled trial is in progress. Ethical principles and careful consideration of the risk-benefit ratio must remain at the forefront of this work with a vulnerable population. However, future research will develop TMS as a research tool for developmental neuroscience and novel treatment in youth struggling with psychiatric diseases.
47 Effects of electrode drift in transcranial direct current stimulation Adam J. Woods PhD a,*, Vaughn Bryant MS a, Daniela Sacchetti MS b, Felix Gervits b, Roy Hamilton MD, MS b a Cognitive Aging and Memory Clinical Translational Research Program, Institute on Aging, Department of Aging and Geriatric Research, University of Florida b Center for Cognitive Neuroscience, Laboratory for Cognition and Neural Stimulation, Department of Neurology, University of Pennsylvania *E-mail: ajwoods@ufl.edu. Conventional transcranial direct current stimulation (tDCS) methods involve application of weak electrical current through electrodes encased in saline soaked sponges affixed to the head using elastic straps. In the absence of careful preparation, electrodes can drift from their original location over the course of a tDCS session. The current research investigates the influence of electrode drift on distribution of electric fields generated by conventional tDCS. We used MRI-derived finite element models of electric fields produced by tDCS to investigate the influence of incremental drift in electrodes for two of the most common electrode montages used in the literature: M1/SO (motor to contralateral supraorbital) and F3/F4 (bilateral frontal). Based on these models, we extracted predicted current intensity from 20 representative structures in the brain. Results from separate RMANOVAs for M1/SO and F3/F4 montages demonstrated that 5% incremental drift in electrode position significantly changed the distribution of current delivered by tDCS to the human brain (F’s > 8.6, p’s<.001). Pairwise comparisons demonstrated that as little as 5% drift was able to produce significant differences in current intensity in structures distributed across the brain (p’s< .03). Drift in electrode position during a session of tDCS produces significant
Abstracts / Brain Stimulation 8 (2015) 310e325
alteration in the intensity of stimulation delivered to the brain. Elimination of this source of variability will facilitate replication and interpretation of tDCS findings. Furthermore, measurement and statistically accounting for drift may prove important for better characterizing the effects of tDCS on the human brain and behavior.
48 Potentiation of anticonvulsants effects by repetitive transcranial magnetic stimulation V. Kistsen a, V. Evstigneev a, B. Dubovik b, V. Ulashchic c a Neurology and Neurosurgery Dept., Belarusian Medical Academy of Postgraduate Education, Minsk, Belarus b Dept of Pharmacology, Belarusian Medical University, Minsk, Belarus c Belarusian Institute of Physiology Objective: The aim of our study was to reveal of repetitive transcranial magnetic stimulation (rTMS) and antiepileptic drugs (AEDs) interaction effects. Methods: The comparative analysis of anticonvulsive effects of rTMS combination with different AEDs was performed by maximal electroshock test (MEST) on Wistar rats which took AEDs in minimal effective doses (ED). rTMS with 1 Hz frequency and subthreshold intensity was completed. Results of combined therapy groups were conferred with monotherapy (AED or rTMS only) and control group (n¼10 in each group). The clinical part of study was designed to evaluate the effect of rTMS by multivoxel 1H-MRS on 28 patients (mean age 28.12.9 years) which take AEDs in minimal therapeutic doses. Results: rTMS has additive effect concerning MTHLE absence when assign with carbamazepine in ED40 in 90% (p¼0.01) and topiramate in ED30 in 80% animals (p¼0.035). Tonic phase duration significant shorten practically in all rTMS+AEDs groups, particular with topiramate (p¼0.002), but had not potentiating effect with gabapentin (p¼0.12). rTMS shortened phase of clonic seizures and total seizure duration for all AEDs (p<0.05). Period after turningover reflex recovery corrected by rTMS in carbamazepine group only (p¼0.04). Normalization of NAA/Cho+Cr after single rTMS was registrated at 50% of patients at real rTMS group (p<0.05). These clinical reduction of seizure frequency were correlated with increases in NAA/Cho+Cr ratio in the ipsilateral hippocampus region after rTMS session (r¼0.7, p¼0.037). For the sham group, there were no any significant changes in NAA/Cho+Cr ratio levels (p>0.1). Conclusions: Thereby, rTMS has an additive effect with AEDs. That effect correlate with neurometabolic effect in deep brain regions and can predict course of epilepsy after complex therapy with lowintensity rTMS. Results of this study can to be a reason to include rTMS in epilepsy treatment with low AEDs dose what can deliver patients from negative side effects.
49 The effect of inactivation of prefrontal cortex on immediate behavioral adaptation in group reversal task by offline repetitive transcranial magnetic stimulation (rTMS) in monkeys Takayuki Hosokawa , Shinya Nakamura , Yuta Matsui , Munekazu Yamada , Toshio Iijima , Ken-Ichiro Tsutsui Division of Systems Neuroscience, Tohoku University Graduate School of Life Sciences To investigate the brain areas related to categorical thinking, we trained two Japanese monkeys (Macaca fuscata) to perform a group reversal task. In this behavioral task, one of eight visual stimuli, half of which were associated with juice and the rest with saline, was chosen to serve as a cue to predict which type of liquid was to be
321
given at the end of the trial. As monkeys learned the stimulusoutcome relation, they showed anticipatory licking after the presentation of a juice-predicting stimulus, and no licking after the presentation of a saline-predicting stimulus. We occasionally reversed the stimulus-outcome relation in all stimuli without any explicit cue. The monkeys showed extremely quick adaptation to the change of this relation after making a single error at the reversal, indicating that they could generalize the relational change experienced for one stimulus for the other stimuli. This result suggests that the monkeys had recognized the stimuli associated with the same outcome as a category. A category of this kind based on experience and learning is termed the “acquired category”, in contrast to the “perceptual category” based on perceptual resemblance. We investigated the functions of the prefrontal areas by inhibiting the neural activity by low-frequency repetitive transcranial magnetic stimulation (rTMS). We separately inactivated the dorsolateral prefrontal cortex (DLPFC), ventrolateral prefrontal cortex (VLPFC), and dorsal prefrontal cortex (dPFC) by applying rTMS bilaterally before the monkeys performed the task (twice for each hemisphere at 1 Hz for 5 minutes). Inactivation of DLPFC or VLPFC, but not of dPFC, impaired the behavioral performance after the reversal: the monkeys needed significantly more trials to adapt their behavior to the reversal. These results suggest that DLPFC and VLPFC play critical roles in behavioral adaptation in group reversal based on acquired category information.
51 Different roles of the monkey dorsolateral prefrontal, premotor and posterior parietal cortices in a delayed response task revealed by functional disturbance by on-line rTMS S. Nakamura , T. Hosokawa , T. Iijima , K.I. Tsutsui Tohoku University, Japan *E-mail: [email protected]. Previous studies have demonstrated that the dorsolateral prefrontal cortex (DLPFC) plays an essential role in short-term memory, the posterior parietal cortex (PPC) forms the multimodal spatial information necessary for action planning and execution, and the premotor cortex (PMC) is involved in planning and preparing a specific motor action on the basis of the information provided from the DLPFC and PPC. However, there are few studies which have examined the functions of these brain areas under identical conditions, such as with the same animal and behavioral task. In this study, we applied repetitive transcranial magnetic stimulation (rTMS) for disturbing the neural activity and examined how the DLPFC, PPC and PMC differentially contributed to the execution of a delayed response task. We trained two monkeys to perform the delayed response task. In the task, one of eight buttons arranged in a circle was illuminated as a cue, and pressing that button after a variable delay was rewarded. 10-Hz 10-pulse rTMS was delivered 0.5 s after the beginning of the delay. The task performance was significantly impaired by rTMS to the DLPFC in a delay-dependent manner when the target button was in the hemifield contralateral to the stimulated hemisphere irrespective of which hand was used. rTMS to the PMC impaired the performance when the monkey used the hand contralateral to the stimulated hemisphere irrespective of the target location. The result of rTMS to the PPC was rather complex, in which the performance was impaired when the monkey reached the target button in the hemifield contralateral to the stimulated hemisphere with the hand contralateral to the target hemifield. These results are consistent with the previous findings and suggest that these brain areas work as separate functional elements for successful performance of the delayed response task.
Abstracts / Brain Stimulation 8 (2015) 310e325
cortical inhibition and facilitation, and silent period) of the stimulated and non-stimulated motor cortex before and after navigated rTMS. rTMS induced a significant increase in excitability in the affected (non-stimulated ) motor cortex (p <0.001) and led to improved performance in the finger tapping task and pinch force task (p < 0.001 and p < 0.002 respectively). These physiological and behavioral effects were more prominent (or robust) in the group of stroke patients than in the control group. Low-frequency rTMS involving precise and consistent targeting of the unaffected hemisphere in stroke patients enhanced the cortical excitability of the affected hemisphere and the motor response of the hemiparetic hand. The effects of rTMS were more robust in patients than in healthy subjects. These findings support that (1) navigated rTMS can improve motor function in stroke, and (2) that pathophysiology following unilateral lesion might positively bias the rTMS response.
45 Contralateral and ipsilateral corticobulbar pathway projections for laryngeal muscles in healthy subjects and patients Marina Zmajevic Schönwald a,*, Maja Rogic Vidakovic b,* a Department of Neurosurgery, Clinical Unit for Intraoperative Neurophysiologic Monitoring, Clinical Medical Centre “Sisters of Mercy”, Zagreb, Croatia b Laboratory for Human and Experimental Neurophysiology (LAHEN), Department of Neuroscience, School of Medicine, University of Split, Croatia, Tel.:+385(0)21 557 876 *E-mail: [email protected], [email protected]. Introduction: Here we present assessment of excitability of contralateral and ipsilateral corticobulbar pathways, using the methodologies of navigated transcranial magnetic stimulation (nTMS) and transcranial electrical stimulation (TES). Methods: In the present study we applied event-related nTMS generating modified patterned nTMS protocol to the primary motor cortex for laryngeal muscle representation of the left and right hemisphere, respectively, and recorded contralateral (left hemisphere stimulation) and ipsilateral (right hemisphere stimulation) corticobulbar motor evoked potentials (CoMEPs) from the right cricothyroid muscle in the group of 11 healthy subjects. In the group of 15 patients under undergoing craniotomy, CoMEPs were recorded from bilateral cricothyroid muscles by applying TES over C3/Cz and C4/Cz. Results: In 5 out of 11 healthy subjects both contralateral and ipsilateral CoMEPs were recorded from right cricothyroid muscle. In 8 out of 15 patients contralateral and ipsilateral CoMEPs were elicited with TES over C3/Cz, while in 5 out of 15 patients contralateral and ipsilateral CoMEPs were elicited with TES over C4/Cz. Contralateral CoMEP amplitude responses were significantly larger compared to ipsilateral CoMEP amplitudes in both groups. Discussions: We obtained significantly larger amplitude responses of contralateral CoMEPs from laryngeal muscles compared to ipsilateral CoMEPs amplitude using nTMS in healthy subjects and TES in patients. This confirms bilateral nature of corticobulbar pathways projections for laryngeal muscles, with contralateral domination. These findings will influence preoperative and intraoperative CoMEPs monitoring and mapping of primary motor cortex for laryngeal muscles, and facilitate neurophysiologic research of motor speech disorders.
46 Transcranial Magnetic Stimulation Neurophysiologic and Therapeutic Studies in Child and Adolescent Depression Paul Croarkin DO, MSCS Assistant Professor of Psychiatry, Mayo Clinic, Rochester, MN, USA
Major Depressive Disorder (MDD) is a common psychiatric disease in childhood which confers substantial morbidity and a significant societal burden. The pathophysiology and optimal treatment of early-onset MDD is poorly understood. Transcranial magnetic stimulation (TMS) is an important tool for therapeutic and neurophysiologic research studies in children and adolescents with mood disorders. This presentation will provide an overview of recent work from the Mayo Clinic Pediatric Neurostimulation lab. Recent neurophysiologic investigations examining youth with MDD and healthy controls include a cross-sectional study of cortical excitability (assessed with motor threshold and intracortical facilitation measures) and inhibition (assessed with shortinterval cortical inhibition and cortical silent period measures). Initial results suggest that children and adolescents with depression have increased glutamatergic intracortical facilitation. Another study examining long-interval cortical inhibition in depressed adolescents initiating treatment with fluoxetine suggests that baseline deficits in long-interval cortical inhibition may be associated with a poor response to fluoxetine. Exploratory work also suggests that motor threshold and long-interval cortical inhibition measures change with age in early life. Our group has now also treated 24 depressed adolescents with high frequency repetitive transcranial magnetic stimulation. (30 sessions of 10 Hz rTMS at 120% motor threshold). In open-label treatment, the mean Children’s Depression Rating Scale Revised score increased over the course of 30 sessions and further at 6 month follow-up. A blinded, randomized, sham-controlled trial is in progress. Ethical principles and careful consideration of the risk-benefit ratio must remain at the forefront of this work with a vulnerable population. However, future research will develop TMS as a research tool for developmental neuroscience and novel treatment in youth struggling with psychiatric diseases.
47 Effects of electrode drift in transcranial direct current stimulation Adam J. Woods PhD a,*, Vaughn Bryant MS a, Daniela Sacchetti MS b, Felix Gervits b, Roy Hamilton MD, MS b a Cognitive Aging and Memory Clinical Translational Research Program, Institute on Aging, Department of Aging and Geriatric Research, University of Florida b Center for Cognitive Neuroscience, Laboratory for Cognition and Neural Stimulation, Department of Neurology, University of Pennsylvania *E-mail: ajwoods@ufl.edu. Conventional transcranial direct current stimulation (tDCS) methods involve application of weak electrical current through electrodes encased in saline soaked sponges affixed to the head using elastic straps. In the absence of careful preparation, electrodes can drift from their original location over the course of a tDCS session. The current research investigates the influence of electrode drift on distribution of electric fields generated by conventional tDCS. We used MRI-derived finite element models of electric fields produced by tDCS to investigate the influence of incremental drift in electrodes for two of the most common electrode montages used in the literature: M1/SO (motor to contralateral supraorbital) and F3/F4 (bilateral frontal). Based on these models, we extracted predicted current intensity from 20 representative structures in the brain. Results from separate RMANOVAs for M1/SO and F3/F4 montages demonstrated that 5% incremental drift in electrode position significantly changed the distribution of current delivered by tDCS to the human brain (F’s > 8.6, p’s<.001). Pairwise comparisons demonstrated that as little as 5% drift was able to produce significant differences in current intensity in structures distributed across the brain (p’s< .03). Drift in electrode position during a session of tDCS produces significant
Abstracts / Brain Stimulation 8 (2015) 310e325
alteration in the intensity of stimulation delivered to the brain. Elimination of this source of variability will facilitate replication and interpretation of tDCS findings. Furthermore, measurement and statistically accounting for drift may prove important for better characterizing the effects of tDCS on the human brain and behavior.
48 Potentiation of anticonvulsants effects by repetitive transcranial magnetic stimulation V. Kistsen a, V. Evstigneev a, B. Dubovik b, V. Ulashchic c a Neurology and Neurosurgery Dept., Belarusian Medical Academy of Postgraduate Education, Minsk, Belarus b Dept of Pharmacology, Belarusian Medical University, Minsk, Belarus c Belarusian Institute of Physiology Objective: The aim of our study was to reveal of repetitive transcranial magnetic stimulation (rTMS) and antiepileptic drugs (AEDs) interaction effects. Methods: The comparative analysis of anticonvulsive effects of rTMS combination with different AEDs was performed by maximal electroshock test (MEST) on Wistar rats which took AEDs in minimal effective doses (ED). rTMS with 1 Hz frequency and subthreshold intensity was completed. Results of combined therapy groups were conferred with monotherapy (AED or rTMS only) and control group (n¼10 in each group). The clinical part of study was designed to evaluate the effect of rTMS by multivoxel 1H-MRS on 28 patients (mean age 28.12.9 years) which take AEDs in minimal therapeutic doses. Results: rTMS has additive effect concerning MTHLE absence when assign with carbamazepine in ED40 in 90% (p¼0.01) and topiramate in ED30 in 80% animals (p¼0.035). Tonic phase duration significant shorten practically in all rTMS+AEDs groups, particular with topiramate (p¼0.002), but had not potentiating effect with gabapentin (p¼0.12). rTMS shortened phase of clonic seizures and total seizure duration for all AEDs (p<0.05). Period after turningover reflex recovery corrected by rTMS in carbamazepine group only (p¼0.04). Normalization of NAA/Cho+Cr after single rTMS was registrated at 50% of patients at real rTMS group (p<0.05). These clinical reduction of seizure frequency were correlated with increases in NAA/Cho+Cr ratio in the ipsilateral hippocampus region after rTMS session (r¼0.7, p¼0.037). For the sham group, there were no any significant changes in NAA/Cho+Cr ratio levels (p>0.1). Conclusions: Thereby, rTMS has an additive effect with AEDs. That effect correlate with neurometabolic effect in deep brain regions and can predict course of epilepsy after complex therapy with lowintensity rTMS. Results of this study can to be a reason to include rTMS in epilepsy treatment with low AEDs dose what can deliver patients from negative side effects.
49 The effect of inactivation of prefrontal cortex on immediate behavioral adaptation in group reversal task by offline repetitive transcranial magnetic stimulation (rTMS) in monkeys Takayuki Hosokawa , Shinya Nakamura , Yuta Matsui , Munekazu Yamada , Toshio Iijima , Ken-Ichiro Tsutsui Division of Systems Neuroscience, Tohoku University Graduate School of Life Sciences To investigate the brain areas related to categorical thinking, we trained two Japanese monkeys (Macaca fuscata) to perform a group reversal task. In this behavioral task, one of eight visual stimuli, half of which were associated with juice and the rest with saline, was chosen to serve as a cue to predict which type of liquid was to be
321
given at the end of the trial. As monkeys learned the stimulusoutcome relation, they showed anticipatory licking after the presentation of a juice-predicting stimulus, and no licking after the presentation of a saline-predicting stimulus. We occasionally reversed the stimulus-outcome relation in all stimuli without any explicit cue. The monkeys showed extremely quick adaptation to the change of this relation after making a single error at the reversal, indicating that they could generalize the relational change experienced for one stimulus for the other stimuli. This result suggests that the monkeys had recognized the stimuli associated with the same outcome as a category. A category of this kind based on experience and learning is termed the “acquired category”, in contrast to the “perceptual category” based on perceptual resemblance. We investigated the functions of the prefrontal areas by inhibiting the neural activity by low-frequency repetitive transcranial magnetic stimulation (rTMS). We separately inactivated the dorsolateral prefrontal cortex (DLPFC), ventrolateral prefrontal cortex (VLPFC), and dorsal prefrontal cortex (dPFC) by applying rTMS bilaterally before the monkeys performed the task (twice for each hemisphere at 1 Hz for 5 minutes). Inactivation of DLPFC or VLPFC, but not of dPFC, impaired the behavioral performance after the reversal: the monkeys needed significantly more trials to adapt their behavior to the reversal. These results suggest that DLPFC and VLPFC play critical roles in behavioral adaptation in group reversal based on acquired category information.
51 Different roles of the monkey dorsolateral prefrontal, premotor and posterior parietal cortices in a delayed response task revealed by functional disturbance by on-line rTMS S. Nakamura , T. Hosokawa , T. Iijima , K.I. Tsutsui Tohoku University, Japan *E-mail: [email protected]. Previous studies have demonstrated that the dorsolateral prefrontal cortex (DLPFC) plays an essential role in short-term memory, the posterior parietal cortex (PPC) forms the multimodal spatial information necessary for action planning and execution, and the premotor cortex (PMC) is involved in planning and preparing a specific motor action on the basis of the information provided from the DLPFC and PPC. However, there are few studies which have examined the functions of these brain areas under identical conditions, such as with the same animal and behavioral task. In this study, we applied repetitive transcranial magnetic stimulation (rTMS) for disturbing the neural activity and examined how the DLPFC, PPC and PMC differentially contributed to the execution of a delayed response task. We trained two monkeys to perform the delayed response task. In the task, one of eight buttons arranged in a circle was illuminated as a cue, and pressing that button after a variable delay was rewarded. 10-Hz 10-pulse rTMS was delivered 0.5 s after the beginning of the delay. The task performance was significantly impaired by rTMS to the DLPFC in a delay-dependent manner when the target button was in the hemifield contralateral to the stimulated hemisphere irrespective of which hand was used. rTMS to the PMC impaired the performance when the monkey used the hand contralateral to the stimulated hemisphere irrespective of the target location. The result of rTMS to the PPC was rather complex, in which the performance was impaired when the monkey reached the target button in the hemifield contralateral to the stimulated hemisphere with the hand contralateral to the target hemifield. These results are consistent with the previous findings and suggest that these brain areas work as separate functional elements for successful performance of the delayed response task.