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P 10. Acute state-dependent changes in corticomotor threshold in the absence of overt motor activity
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Society Proceedings / Clinical Neurophysiology 124 (2013) e39–e187
first dorsal interosseous muscle (FDI) and abductor pollicis brevis (APB). The analyzed cSPs were induced at eight different SIs normalized to the rMT of each subject (60, 70, 80, 90, 100, 110, 120, 130 % of rMT). 10 trials were performed at each SI in a randomized sequence at an inter-trial interval of 12 s. During the TMS, subjects were asked to keep a constant contraction of the target muscles against resistance of approximately 1 mV of peak-to-peak EMG. Late cSPs were identified with a minimum duration of 10 ms and maximum difference of 50 ms between the offset of cSP and onset of late cSP. The late cSPs were analyzed by taking the mean duration at each SI for all the individual subjects. To confirm the presence of late cSPs at different SIs, we used ANOVA with normalized SI as fixed factor and subject as random factor. Post-hoc tests for the SI effect were analyzed and p-values were adjusted with least significant difference (LSD). Results: We found that the time between the offset of the cSP and the onset of the late cSP was40 ms. ANOVA confirmed that late cSPs were present in most subjects. The SI had a significant effect on the appearance of the late cSP in EMG recorded both from FDI (F = 4.504, p = 001, Fig. 2) and from APB (F = 3.882, p = 002). The post hoc test revealed that SI had a significant effect on the appearance of late cSPs at certain SIs (Fig. 2). Especially, TMS with SIs close to rMT was able to induce a late cSP, while at higher SIs the late cSPs disappeared. Conclusion: We have confirmed the appearance of late cSP at SIs around rMT. The origin of the late cSP is not yet known and requires further investigation.
Fig. 1. Demonstration of cSP and late cSP at subthreshold SI.
Fig. 2. Group mean of the late cSP duration as a function of normalized SI. The grey area surrounding the group mean represents standard error. SIs at which the late cSPs were confirmed statistically to appear are indicated by red dots. The level of significance based on the post-hoc test is also indicated above the red dots.
References Fuhr et al. (1991). Orth et al. (2003). Kessler et al. (2002). Hess et al. (1987). Roick et al. (1993). Rossini (1990). Uozumi et al. (1992). doi:10.1016/j.clinph.2013.04.088
P 10. Acute state-dependent changes in corticomotor threshold in the absence of overt motor activity—A. Karabanov, E. Raffin, H. Siebner (DRCMR, Hvidovre, Denmark) Background: The cortical motor threshold (CMT) is often used to individually adjust the intensity of transcranial magnetic stimulation
(TMS). It reflects the integrated excitability of the corticomotor projection, including the excitability at the spinal level. The CMT reflects axonal and synaptic excitability as CMT can be modified by drugs that voltage-gated sodium channel blockers or non-NMDA glutamatergic drugs. Aims and hypothesis: The CMT is not a static measure but is subject to state-dependent fluctuations. To test this hypothesis we used an adaptive stair-case procedure to track acute changes in CMT associated with motor imagery (MI) or shifts in visuospatial attention (VA). Method: Eight healthy subjects were asked to imagine a continuous thumb-index movement with the left or right hand (MI-left and MI-right), to shift their visuospatial attention to the left or right FDI (VA-left and VA-right) or to fixate a cross in the central visual field. Using a fast (<15 pulses) threshold-hunting procedure (Borckardt, 2006), we assessed task-dependent CMT changes in the left primary
Society Proceedings / Clinical Neurophysiology 124 (2013) e39–e187
motor hand area (M1) during each task. CMT was defined as the stimulus intensity, at which a single TMS pulse elicited a MEP of 50 lV in the relaxed right first dorsal interosseus muscle (FDI) with a probability of 0.5. The CMT measurements during the VA and MI task were normalized to the control condition. All participants underwent two experimental sessions on separate days, in which the TMS pulse either induced a posterior-to-anterior (PA) or anterior-to-posterior (AP) current in M1. Results: The number of pulses needed to determine rMT did not significantly differ across conditions (average: 13.5). Using the normalized CMT values as dependent variable, we computed a repeated measures ANOVA with the factors Current (AP/PA), Task (MI/VA) and Site (Left/Right). We found a significant Task-by-Site interaction (p = 0.004). Post hoc testing confirmed that CMT during MI-right was significantly lower than during MI-left or during VAright. This was the case for AP and PA current direction. Discussion: The resting CMT is subject to rapid state-dependent changes in the absence of overt motor activity. We show that these acute CMT changes can be captured with a threshold-hunting procedure. The “CMT tracking” approach might be particularly useful to assess the temporal dynamics of corticomotor excitability changes induced by interventional brain stimulation protocols. doi:10.1016/j.clinph.2013.04.089
P 11. Cortical inhibition within motor and frontal regions in alcohol dependence: A TMS–EEG study—J. Naim-Feil a,b, J.L. Bradshaw c, N. Rogasch a, Z.J. Daskalakis a,d, D. Sheppard e, D.I. Lubman f, P.B. Fitzgerald a (a Monash University, Monash Alfred Psychiatry Research Centre, Melbourne, Australia, b Weizmann Institute of Science, Physics of Complex Systems, Rehovot, Australia, c Monash University, Experimental Neuropsychology Research Unit, Melbourne, Australia, d Centre for Addiction and Mental Health, University of Toronto, Toronto, Canada, e Monash Injury Research Institute, Melbourne, Australia, f Turning Point Alcohol and Drug Centre, Melbourne, Australia) Background: Preclinical studies suggest that alterations within the frontal cortex play a critical role in the neurophysiology of alcohol dependence. The combination of transcranial magnetic stimulation and electroencephalography (TMS-EEG) allows a direct assessment of cortical excitability and inhibition within the frontal cortex in human subjects. We report the first application of TMS-EEG to measure these indices within the frontal cortices of patients with alcohol dependence. Methods: Cortical inhibition was assessed in 12 patients with alcohol dependence and 14 healthy controls through single and pairedpulse transcranial magnetic stimulations (TMS) paradigms delivered to both the frontal and motor cortices. Long interval cortical inhibition (LICI) was used to index inhibition in the frontal cortex. Short intracortical inhibition (SICI) and cortical silent period (CSP) was used to index inhibition, while intracortical facilitation (ICF) measured facilitation, in the motor cortex. Cortical excitability was indexed by the resting motor threshold (RMT) and active motor threshold (AMT). Results: The alcohol dependent group demonstrated deficits in LICI across both the left and right dorsolateral prefrontal cortex relative to healthy controls. The alcohol dependent group also exhibited reduced RMT and AMT. In terms of motor cortex inhibition, there were no significant differences in SICI, ICF or CSP, although increased intra-trial-variability in SICI was observed in the alcohol dependent group. Conclusions: The current study provides the first direct evidence of reduced cortical inhibition that is specific to the frontal cortex of patients with alcohol dependence. Our study also revealed evidence
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of altered cortical excitability in the motor cortex of patients with alcohol dependence; however, the utility of using the motor cortex to index cortical alterations related to alcohol dependence remains unclear. Although these findings are preliminary, they provide critical neurophysiological evidence of disrupted cortical excitability within the frontal cortex of alcohol dependent patients. doi:10.1016/j.clinph.2013.04.090
P 12. Transcranial alternating current stimulation enhances endogenous alpha for 30 min only for moderate alpha levels—T. Neuling, S. Rach, C. Herrmann (Carl von Ossietzky Universität Oldenburg, Department for Experimental Psychology, Oldenburg, Germany) Introduction: Transcranial alternating current stimulation (tACS) has been proven to successfully influence endogenous brain oscillations in a frequency specific manner (Zaehle et al., 2010). Besides effects on the electrophysiology, tACS is also able to influence perception and behavior (Neuling et al., 2012). After tACS, the endogenous power of the stimulated frequency is enhanced when compared a pre-stimulation period, however, little is known about the duration of this effect and which parameters contribute to this effect. Objectives: Our goal was to discern how long endogenous brain oscillations are enhanced post tACS and how pre-stimulation power of the oscillation modulates this effect. Materials and methods: Two experiments were conducted whereby subjects had their eyes either open or closed. Experimental procedure is demonstrated in Fig. 1. Participants were stimulated with their individual alpha frequency (IAF) for 20 min or received sham stimulation. Stimulation electrode positions were chosen in order to effect occipital alpha (Neuling et al., 2012). Five minutes before (pre) and 30 min after stimulation (post), the electroencephalogram (EEG) was recorded. During the experiment, subjects performed a simple auditory detection task to ensure vigilance (Fig. 1C). Results: In the eyes closed experiment, no effects on the oscillatory power could be demonstrated (Fig. 2AI). After stimulation, both in the stimulation and in the sham group, IAF power was not significantly different than pre-stimulation levels (Fig. 2BI). Likewise, no significant effects in the entire post period could be revealed (Fig. 2CI). Contrary to the results in the eyed closed experiment, an effect on the oscillatory power, limited to the alpha range, was found in the eyes open experiment (Fig. 2AII). The power increase from the pre-to the post stimulation period was significant in the stimulated group, but not in the sham group (Fig. 2BII). This enhancement effect was significant over the entire30 min post-stimulation recording (Fig. 2CII). Conclusion: If the endogenous alpha oscillations are high, stimulation with tACS fails to increase alpha power due to ceiling effects. The neuronal network activity is unaffected by external oscillations, at least in terms of oscillatory power. Endogenous oscillations exhibiting lower power are more prone to effects of tACS. Here, tACS is able to enhance endogenous oscillations over a long duration. It might be speculated that the enhancement effect would last even longer than 30 min. The results of our study illustrate the feasibility of tACS as a tool for non-invasive brain stimulation and demonstrate the potential for therapeutic application to balance altered brain oscillations. References Zaehle T, Rach S, Herrmann CS. Transcranial alternating current stimulation enhances individual alpha activity in human EEG. PLoS One 2010;5:e13766. Neuling T, Rach S, Wagner S, Wolters CH, Herrmann CS. Good vibrations: oscillatory phase shapes perception. NeuroImage 2012;63:771–8.
Society Proceedings / Clinical Neurophysiology 124 (2013) e39–e187
first dorsal interosseous muscle (FDI) and abductor pollicis brevis (APB). The analyzed cSPs were induced at eight different SIs normalized to the rMT of each subject (60, 70, 80, 90, 100, 110, 120, 130 % of rMT). 10 trials were performed at each SI in a randomized sequence at an inter-trial interval of 12 s. During the TMS, subjects were asked to keep a constant contraction of the target muscles against resistance of approximately 1 mV of peak-to-peak EMG. Late cSPs were identified with a minimum duration of 10 ms and maximum difference of 50 ms between the offset of cSP and onset of late cSP. The late cSPs were analyzed by taking the mean duration at each SI for all the individual subjects. To confirm the presence of late cSPs at different SIs, we used ANOVA with normalized SI as fixed factor and subject as random factor. Post-hoc tests for the SI effect were analyzed and p-values were adjusted with least significant difference (LSD). Results: We found that the time between the offset of the cSP and the onset of the late cSP was40 ms. ANOVA confirmed that late cSPs were present in most subjects. The SI had a significant effect on the appearance of the late cSP in EMG recorded both from FDI (F = 4.504, p = 001, Fig. 2) and from APB (F = 3.882, p = 002). The post hoc test revealed that SI had a significant effect on the appearance of late cSPs at certain SIs (Fig. 2). Especially, TMS with SIs close to rMT was able to induce a late cSP, while at higher SIs the late cSPs disappeared. Conclusion: We have confirmed the appearance of late cSP at SIs around rMT. The origin of the late cSP is not yet known and requires further investigation.
Fig. 1. Demonstration of cSP and late cSP at subthreshold SI.
Fig. 2. Group mean of the late cSP duration as a function of normalized SI. The grey area surrounding the group mean represents standard error. SIs at which the late cSPs were confirmed statistically to appear are indicated by red dots. The level of significance based on the post-hoc test is also indicated above the red dots.
References Fuhr et al. (1991). Orth et al. (2003). Kessler et al. (2002). Hess et al. (1987). Roick et al. (1993). Rossini (1990). Uozumi et al. (1992). doi:10.1016/j.clinph.2013.04.088
P 10. Acute state-dependent changes in corticomotor threshold in the absence of overt motor activity—A. Karabanov, E. Raffin, H. Siebner (DRCMR, Hvidovre, Denmark) Background: The cortical motor threshold (CMT) is often used to individually adjust the intensity of transcranial magnetic stimulation
(TMS). It reflects the integrated excitability of the corticomotor projection, including the excitability at the spinal level. The CMT reflects axonal and synaptic excitability as CMT can be modified by drugs that voltage-gated sodium channel blockers or non-NMDA glutamatergic drugs. Aims and hypothesis: The CMT is not a static measure but is subject to state-dependent fluctuations. To test this hypothesis we used an adaptive stair-case procedure to track acute changes in CMT associated with motor imagery (MI) or shifts in visuospatial attention (VA). Method: Eight healthy subjects were asked to imagine a continuous thumb-index movement with the left or right hand (MI-left and MI-right), to shift their visuospatial attention to the left or right FDI (VA-left and VA-right) or to fixate a cross in the central visual field. Using a fast (<15 pulses) threshold-hunting procedure (Borckardt, 2006), we assessed task-dependent CMT changes in the left primary
Society Proceedings / Clinical Neurophysiology 124 (2013) e39–e187
motor hand area (M1) during each task. CMT was defined as the stimulus intensity, at which a single TMS pulse elicited a MEP of 50 lV in the relaxed right first dorsal interosseus muscle (FDI) with a probability of 0.5. The CMT measurements during the VA and MI task were normalized to the control condition. All participants underwent two experimental sessions on separate days, in which the TMS pulse either induced a posterior-to-anterior (PA) or anterior-to-posterior (AP) current in M1. Results: The number of pulses needed to determine rMT did not significantly differ across conditions (average: 13.5). Using the normalized CMT values as dependent variable, we computed a repeated measures ANOVA with the factors Current (AP/PA), Task (MI/VA) and Site (Left/Right). We found a significant Task-by-Site interaction (p = 0.004). Post hoc testing confirmed that CMT during MI-right was significantly lower than during MI-left or during VAright. This was the case for AP and PA current direction. Discussion: The resting CMT is subject to rapid state-dependent changes in the absence of overt motor activity. We show that these acute CMT changes can be captured with a threshold-hunting procedure. The “CMT tracking” approach might be particularly useful to assess the temporal dynamics of corticomotor excitability changes induced by interventional brain stimulation protocols. doi:10.1016/j.clinph.2013.04.089
P 11. Cortical inhibition within motor and frontal regions in alcohol dependence: A TMS–EEG study—J. Naim-Feil a,b, J.L. Bradshaw c, N. Rogasch a, Z.J. Daskalakis a,d, D. Sheppard e, D.I. Lubman f, P.B. Fitzgerald a (a Monash University, Monash Alfred Psychiatry Research Centre, Melbourne, Australia, b Weizmann Institute of Science, Physics of Complex Systems, Rehovot, Australia, c Monash University, Experimental Neuropsychology Research Unit, Melbourne, Australia, d Centre for Addiction and Mental Health, University of Toronto, Toronto, Canada, e Monash Injury Research Institute, Melbourne, Australia, f Turning Point Alcohol and Drug Centre, Melbourne, Australia) Background: Preclinical studies suggest that alterations within the frontal cortex play a critical role in the neurophysiology of alcohol dependence. The combination of transcranial magnetic stimulation and electroencephalography (TMS-EEG) allows a direct assessment of cortical excitability and inhibition within the frontal cortex in human subjects. We report the first application of TMS-EEG to measure these indices within the frontal cortices of patients with alcohol dependence. Methods: Cortical inhibition was assessed in 12 patients with alcohol dependence and 14 healthy controls through single and pairedpulse transcranial magnetic stimulations (TMS) paradigms delivered to both the frontal and motor cortices. Long interval cortical inhibition (LICI) was used to index inhibition in the frontal cortex. Short intracortical inhibition (SICI) and cortical silent period (CSP) was used to index inhibition, while intracortical facilitation (ICF) measured facilitation, in the motor cortex. Cortical excitability was indexed by the resting motor threshold (RMT) and active motor threshold (AMT). Results: The alcohol dependent group demonstrated deficits in LICI across both the left and right dorsolateral prefrontal cortex relative to healthy controls. The alcohol dependent group also exhibited reduced RMT and AMT. In terms of motor cortex inhibition, there were no significant differences in SICI, ICF or CSP, although increased intra-trial-variability in SICI was observed in the alcohol dependent group. Conclusions: The current study provides the first direct evidence of reduced cortical inhibition that is specific to the frontal cortex of patients with alcohol dependence. Our study also revealed evidence
e69
of altered cortical excitability in the motor cortex of patients with alcohol dependence; however, the utility of using the motor cortex to index cortical alterations related to alcohol dependence remains unclear. Although these findings are preliminary, they provide critical neurophysiological evidence of disrupted cortical excitability within the frontal cortex of alcohol dependent patients. doi:10.1016/j.clinph.2013.04.090
P 12. Transcranial alternating current stimulation enhances endogenous alpha for 30 min only for moderate alpha levels—T. Neuling, S. Rach, C. Herrmann (Carl von Ossietzky Universität Oldenburg, Department for Experimental Psychology, Oldenburg, Germany) Introduction: Transcranial alternating current stimulation (tACS) has been proven to successfully influence endogenous brain oscillations in a frequency specific manner (Zaehle et al., 2010). Besides effects on the electrophysiology, tACS is also able to influence perception and behavior (Neuling et al., 2012). After tACS, the endogenous power of the stimulated frequency is enhanced when compared a pre-stimulation period, however, little is known about the duration of this effect and which parameters contribute to this effect. Objectives: Our goal was to discern how long endogenous brain oscillations are enhanced post tACS and how pre-stimulation power of the oscillation modulates this effect. Materials and methods: Two experiments were conducted whereby subjects had their eyes either open or closed. Experimental procedure is demonstrated in Fig. 1. Participants were stimulated with their individual alpha frequency (IAF) for 20 min or received sham stimulation. Stimulation electrode positions were chosen in order to effect occipital alpha (Neuling et al., 2012). Five minutes before (pre) and 30 min after stimulation (post), the electroencephalogram (EEG) was recorded. During the experiment, subjects performed a simple auditory detection task to ensure vigilance (Fig. 1C). Results: In the eyes closed experiment, no effects on the oscillatory power could be demonstrated (Fig. 2AI). After stimulation, both in the stimulation and in the sham group, IAF power was not significantly different than pre-stimulation levels (Fig. 2BI). Likewise, no significant effects in the entire post period could be revealed (Fig. 2CI). Contrary to the results in the eyed closed experiment, an effect on the oscillatory power, limited to the alpha range, was found in the eyes open experiment (Fig. 2AII). The power increase from the pre-to the post stimulation period was significant in the stimulated group, but not in the sham group (Fig. 2BII). This enhancement effect was significant over the entire30 min post-stimulation recording (Fig. 2CII). Conclusion: If the endogenous alpha oscillations are high, stimulation with tACS fails to increase alpha power due to ceiling effects. The neuronal network activity is unaffected by external oscillations, at least in terms of oscillatory power. Endogenous oscillations exhibiting lower power are more prone to effects of tACS. Here, tACS is able to enhance endogenous oscillations over a long duration. It might be speculated that the enhancement effect would last even longer than 30 min. The results of our study illustrate the feasibility of tACS as a tool for non-invasive brain stimulation and demonstrate the potential for therapeutic application to balance altered brain oscillations. References Zaehle T, Rach S, Herrmann CS. Transcranial alternating current stimulation enhances individual alpha activity in human EEG. PLoS One 2010;5:e13766. Neuling T, Rach S, Wagner S, Wolters CH, Herrmann CS. Good vibrations: oscillatory phase shapes perception. NeuroImage 2012;63:771–8.