- Email: [email protected]
Central motor conduction examined with the triple stimulation technique correlates with pyramidal tract dysfunction and disability in patients with multiple sclerosis
Society Proceedings / Clinical Neurophysiology 118 (2007) e9–e116
Decreased phase shift between neck suction induced blood pressure and cerebral blood flow velocity oscillations indicates impaired cerebral autoregulation in type II diabetics— M.J. Hilz 1, U. Zikeli 1, R. Baltadzhieva 1, N. Dimitriov 2,3, C.M. Brown 1, H. Marthol 1 (1 Department of Neurology, University of Erlangen-Nuremberg, Erlangen, Germany Hospital St. Naum, Medical University, Sofia, Bulgaria, 2 Department of Neurology, University of ErlangenNuremberg, Erlangen, Germany, 3 Hospital St. Naum, Medical University, Sofia, Bulgaria) Introduction: Compromised cerebral autoregulation (CA) contributes to cerebrovascular complications in diabetic patients. In patients with diabetic cardiac autonomic neuropathy (CAN), standard methods of CA evaluation often fail to objectify the quality of CA. 0.1 Hz sinusoidal neck suction (NS) is a refined technique to quantify CA using transfer function analysis and calculation of the gain and phase shift between NS induced blood pressure (BP) and cerebral blood flow velocity (CBFV) oscillations. Objective: To determine whether NS is suited to objectify CA in diabetic patients with CAN. Methods: In 9 type II diabetics with pre-existing CAN (57 ± 7 years) and 11 age-matched controls (59 ± 11 years), we continuously recorded RR-intervals (RRI), mean BP and mean middle cerebral artery CBFV at rest and during 0.1 Hz sinusoidal NS ( 30 mmHg). We determined BP and CBFV responses to NS from spectral powers of BP and CBFV oscillations at 0.1 Hz at rest and during NS and calculated the 0.1 Hz transfer function gain and phase shift between BP and CBFV oscillations as parameters of CA for coherence >0.5. We compared parameters before and during NS using the Wilcoxon-test, and patient and control data by the U-test. Significance was set at p < 0.05. Results: In both groups, NS did not significantly influence RRI, BP and CBFV. NS significantly increased 0.1 Hz powers of BP (0.6 ± 0.4 vs. 1.3 ± 0.9 mmHg2) and CBFV (0.6 ± 0.5 vs. 1.5 ± 1.0 cm2/s2/mmHg2) in the controls, but not in the patients. The gain between 0.1 Hz BP and CBFV oscillations remained stable in both groups. Phase shift remained stable in controls but decreased in patients ( 1.1 ± 0.7 rad vs. 1.7 ± 0.5 rad). Conclusion: In our patients, the lack of 0.1 Hz power increase of BP and CBFV oscillations was due to CAN. Thus, gain analysis failed to show altered CA. In contrast, phase shift analysis revealed a decrease in patients and identified altered CA in the diabetics. To summarize, 0.1 Hz NS and analysis of phase shift between 0.1 Hz BP and CBFV oscillations is suited to identify subtle impairment of CA in diabetics in the presence of coexisting CAN, even if gain analysis fails to identify abnormal CA. doi:10.1016/j.clinph.2006.11.115
Treadmill training induced improvement of spinal reflex modulation in children with cerebral palsy—M. Hodapp 1, J. Vry 2, V. Mall 2, M. Faist 1 (1 Neurologie, Universita¨tsklinikum, Freiburg, 2 Neuropa¨diatrie, Universita¨tsklinikum, Freiburg) Objectives: In healthy children short latency leg muscle reflexes are profoundly modulated throughout the step cycle in a func-
e47
tionally meaningful way and contribute to the EMG pattern observed during gait. With the maturation of the corticospinal tract the reflex amplitudes are depressed by supraspinal inhibitory mechanisms. For the soleus muscle the modulation pattern shows a relative maximum in the mid-stance phase and a complete depression during the swing phase. In a recent study, we could show, that the rhythmic part of the modulation pattern is present in children with early bilateral supraspinal lesion but compared to healthy children the reflexes were less depressed with increasing age and during the swing phase still reflexes were present. Treadmill training improves clinically the walking pattern in children with cerebral palsy (CP). Presuming that short latency reflexes contribute significantly to the walking pattern a change in the modulation may occur after training. The aim of the present study was to assess whether treadmill training improves the soleus reflex modulation during gait in CP. Methods: Seven children (aged 6–16 years) with diplegic CP underwent a brief treadmill training of 10 min daily for 14 consecutive days. All of them were functional walkers. Before the first and one day after the last training session soleus Hoffmann (H-) reflexes were investigated during walking on a treadmill. Reflex amplitudes were normalized with respect to the maximum motor response (Mmax). Reflexes were obtained during eight different phases of the step cycle. Results: Clinically treadmill training improved gait velocity and step length. Soleus H-reflexes before treadmill training were modulated rhythmically with a relative maximum during midstance and smaller amplitudes during the swing phase. After treadmill training reflexes were almost completely depressed during the swing phase. Conclusion: The present data show that treadmill training can induce changes in the modulation of short latency reflexes during gait. The complete suppression of the soleus H-reflex during the swing phase similar to healthy subjects could reflect an improvement towards a functionally more useful pattern. doi:10.1016/j.clinph.2006.11.116
Central motor conduction examined with the triple stimulation technique correlates with pyramidal tract dysfunction and disability in patients with multiple sclerosis—U. Hofstadt-van Oy, D. Hagenburger, C. Klawe, K. Schro¨der (Abt. fu¨ r Neurologie, Krankenhaus der Barmherzigen Bru¨ der, Trier, Germany) Inflammatory lesions and axonal degeneration of central motor conduction pathways result in gait disturbance and contributes particularly to increasing disability in patients with multiple sclerosis. With conventional transcranial magnetic stimulation central conduction times can be estimated but axonal damage or conduction block of motor pathways is less sensitively detected to correlate well with disability. The triple stimulation technique (TST) examines the corticospinal tract by magnetic stimulation of cortical motor areas followed by sequenced distal and proximal peripheral nerve electric stimulation. The originating potential is a result of the collison of the sequenced stimuli. Then the TSTpotential is compared with sequential stimulation of peripheral nerves alone. With the resulting amplitude ratio central conduction failure can be quantified by TST.
e48
Society Proceedings / Clinical Neurophysiology 118 (2007) e9–e116
Methods: Upper limb (to abductor digiti minimi muscle) and lower limb (to abductor hallucis muscle) TST was applied to 40 healthy volunteers to establish normal values. Sixty patients with relapsing remitting, secondary progressive and primary progressive multiple sclerosis underwent neurological examination including classification in the expanded disability status score (EDSS) according to Kurtzke and in the multiple sclerosis functional composite score (MSFC) including the nine hole peg test and timed walking distance to quantify upper und lower limb function. Results: The EDSS of patients varied between 0 and 8, 5. Central conduction failure quantified with TST correlated significantly with the functional system score for pyramidal tract dysfunction of the EDSS and the upper and lower limb motor tests of the MSCF. In higher EDSS ranges >3, 5 correlations were also proved. Conclusion: TST is a useful method to examine central conduction failure in different stages of disability in patients with Multiple sclerosis and correlates well with clinical deficits and disability scales reflecting motor involvement. doi:10.1016/j.clinph.2006.11.117
Interhemispheric interactions between M1 and PM during movement preparation—J. Hoppe, F. Hummel, H. Huber, D. Weiss, C. Gerloff (Neurologische Universita¨tsklinik, Tu¨bingen, Hertie Institut, fu¨r klinische Hirnforschung) Precise interhemispheric interactions constitute a necessary neural basis for bimanual and complex unimanual coordination, because integration of sensorimotor information of both hemispheres is required. At rest, the effect of interhemispheric interactions between homologous motor cortices (M1) is largely inhibitory (Gerloff et al., 1998. J Physiol (Lond) 510, 249–259). In the process of the generation of a movement, interhemispheric inhibition (IHI) between the M1 ipsilateral to the moving hand (iM1) and the M1 contralateral to the moving hand (cM1) turns into facilitation (‘release of IHI’) close to movement onset (Murase et al., 2004. Ann Neurol 55, 400–409). Anatomical studies suggest that callosal connections between homologous M1 are sparse. In fact, denser connectivity exists between premotor cortex (PM) and M1 of the opposite hemisphere (Rouiller et al., 1994. Exp Brain Res 102, 227–243). As an electrophysiological correlate of the latter, IHI has also been shown between PM and M1 (Mochizuki et al., 2004. J Physiol (Lond) 561, 331–338). In the present study, we set out to evaluate the movement-related dynamic modulation of IHI between the PM ipsilateral to the moving hand (iPM) and cM1. Specifically, we hypothesized that IHI from PM to cM1 is modulated earlier that IHI from iM1 to cM1, following a, in part, serial model of premotor and primary motor cortex activation (e.g., Gerloff et al., 1998. J. Clin. Neurophysiol. 15, 502–513). IHI between iPM and cM1 as well as iM1 and cM1 was studied in 14 healthy subjects during a simple reaction time task using with an established bi-hemispheric double-pulse TMS paradigm (Murase et al., 2004. Ann. Neurol. 55, 400–409). The conditioning stimulus was either applied over the right iPM (PM-IHI) or the right M1 (M1-IHI) ipsilateral to the moving right hand. The test stimulus was always applied over the left M1. At the earliest time point immediately after the go-signal comparable IHI was found with iPM and iM1 conditioning stimula-
tion. Over time, IHI was reduced close to movement onset in both conditions (ANOVA, factor TIME, p < 0.001). However there was a significant difference between M1-IHI and PM-IHI (ANOVA, p = 0.02) with an earlier reduction of IHI following PM stimulation compared with M1 stimulation. Whereas serial processing steps in the PM and M1 of the hemisphere contralateral to the moving hand are well accepted, the present data extends this view to interhemispheric interactions. doi:10.1016/j.clinph.2006.11.118
Context-related motor control implemented by modulation of cortical synchrony: A mechanism of successful context-related motor behavior—F. Hummel 1, F. Hummel 1, P. Sauseng 2, J. Hoppe 1, W. Klimesch 2, C. Gerloff 1 (1 Cortical Physiology Research Group, Department of Neurology and Hertie Institute for Clinical Brain Research, EberhardKarls University Tuebingen, Germany, 2 Institute of Psychology, University of Salzburg, Austria) Modulation of learned ‘‘motor programs’’ is the basis of context-adequate behavior, consisting of retrieval or non-retrieval (inhibition) of behavioral elements. Evidence was provided that focal activation/deactivation represents contextual modulation (Hummel, NIMG 2004). However, it remains open, how involved brain areas interact to implement retrieval and non-retrieval (inhibition). To address these questions phase coherence analysis was used to determine interactions between these brain areas. We evaluated EEG task-related phase coherence (TRPhCoh) and power (TRPow). Subjects trained finger movement sequences until they reached an overlearned level (MEM). The main experimental session consisted of 4 conditions: SEQUENCE (MEM vs. NOV [novel sequences of comparable complexity]) and CONTEXT (MOVE [subjects had to perform MEM or NOV] vs. NO-MOVE [subjects were asked not to perform]. The analysis was focused onto the upper a-band (10–13 Hz) (Hummel, Brain 2002). Task-related phase coherence: During MOVE performance of MEM and NOV revealed comparable TRPhCoh increases obtained in a network comprising prefrontal, sensorimotor and posterior parietal cortex. During NO-MOVE however, MEM showed significant decreases of TRPhCoh below baseline in the same network, which was not the case for NOV. Furthermore, a conjunction analysis between MOVE-MEM and NO-MOVEMEM revealed a network comprising prefrontal, posterior parietal and especially left sensorimotor cortex which showed enhanced coupling during MOVE and decoupling during NO-MOVE. Task-related power: During MOVE performance of MEM and NOV induced TRPow decreases obtained from sensorimotor cortex. During NO-MOVE performance of MEM and NOV induced TRPow increases. The present data suggest that modulation of cortical synchrony (coupling, decoupling) might be an underlying mechanism by which the brain implements successful context-related motor behavior. During retrieval of learned and novel motor acts activation of a fronto-centro-parietal network is implemented by enhanced phase coupling. The present data further indicate that deactivation during non-retrieval of learned motor acts is imple-
Decreased phase shift between neck suction induced blood pressure and cerebral blood flow velocity oscillations indicates impaired cerebral autoregulation in type II diabetics— M.J. Hilz 1, U. Zikeli 1, R. Baltadzhieva 1, N. Dimitriov 2,3, C.M. Brown 1, H. Marthol 1 (1 Department of Neurology, University of Erlangen-Nuremberg, Erlangen, Germany Hospital St. Naum, Medical University, Sofia, Bulgaria, 2 Department of Neurology, University of ErlangenNuremberg, Erlangen, Germany, 3 Hospital St. Naum, Medical University, Sofia, Bulgaria) Introduction: Compromised cerebral autoregulation (CA) contributes to cerebrovascular complications in diabetic patients. In patients with diabetic cardiac autonomic neuropathy (CAN), standard methods of CA evaluation often fail to objectify the quality of CA. 0.1 Hz sinusoidal neck suction (NS) is a refined technique to quantify CA using transfer function analysis and calculation of the gain and phase shift between NS induced blood pressure (BP) and cerebral blood flow velocity (CBFV) oscillations. Objective: To determine whether NS is suited to objectify CA in diabetic patients with CAN. Methods: In 9 type II diabetics with pre-existing CAN (57 ± 7 years) and 11 age-matched controls (59 ± 11 years), we continuously recorded RR-intervals (RRI), mean BP and mean middle cerebral artery CBFV at rest and during 0.1 Hz sinusoidal NS ( 30 mmHg). We determined BP and CBFV responses to NS from spectral powers of BP and CBFV oscillations at 0.1 Hz at rest and during NS and calculated the 0.1 Hz transfer function gain and phase shift between BP and CBFV oscillations as parameters of CA for coherence >0.5. We compared parameters before and during NS using the Wilcoxon-test, and patient and control data by the U-test. Significance was set at p < 0.05. Results: In both groups, NS did not significantly influence RRI, BP and CBFV. NS significantly increased 0.1 Hz powers of BP (0.6 ± 0.4 vs. 1.3 ± 0.9 mmHg2) and CBFV (0.6 ± 0.5 vs. 1.5 ± 1.0 cm2/s2/mmHg2) in the controls, but not in the patients. The gain between 0.1 Hz BP and CBFV oscillations remained stable in both groups. Phase shift remained stable in controls but decreased in patients ( 1.1 ± 0.7 rad vs. 1.7 ± 0.5 rad). Conclusion: In our patients, the lack of 0.1 Hz power increase of BP and CBFV oscillations was due to CAN. Thus, gain analysis failed to show altered CA. In contrast, phase shift analysis revealed a decrease in patients and identified altered CA in the diabetics. To summarize, 0.1 Hz NS and analysis of phase shift between 0.1 Hz BP and CBFV oscillations is suited to identify subtle impairment of CA in diabetics in the presence of coexisting CAN, even if gain analysis fails to identify abnormal CA. doi:10.1016/j.clinph.2006.11.115
Treadmill training induced improvement of spinal reflex modulation in children with cerebral palsy—M. Hodapp 1, J. Vry 2, V. Mall 2, M. Faist 1 (1 Neurologie, Universita¨tsklinikum, Freiburg, 2 Neuropa¨diatrie, Universita¨tsklinikum, Freiburg) Objectives: In healthy children short latency leg muscle reflexes are profoundly modulated throughout the step cycle in a func-
e47
tionally meaningful way and contribute to the EMG pattern observed during gait. With the maturation of the corticospinal tract the reflex amplitudes are depressed by supraspinal inhibitory mechanisms. For the soleus muscle the modulation pattern shows a relative maximum in the mid-stance phase and a complete depression during the swing phase. In a recent study, we could show, that the rhythmic part of the modulation pattern is present in children with early bilateral supraspinal lesion but compared to healthy children the reflexes were less depressed with increasing age and during the swing phase still reflexes were present. Treadmill training improves clinically the walking pattern in children with cerebral palsy (CP). Presuming that short latency reflexes contribute significantly to the walking pattern a change in the modulation may occur after training. The aim of the present study was to assess whether treadmill training improves the soleus reflex modulation during gait in CP. Methods: Seven children (aged 6–16 years) with diplegic CP underwent a brief treadmill training of 10 min daily for 14 consecutive days. All of them were functional walkers. Before the first and one day after the last training session soleus Hoffmann (H-) reflexes were investigated during walking on a treadmill. Reflex amplitudes were normalized with respect to the maximum motor response (Mmax). Reflexes were obtained during eight different phases of the step cycle. Results: Clinically treadmill training improved gait velocity and step length. Soleus H-reflexes before treadmill training were modulated rhythmically with a relative maximum during midstance and smaller amplitudes during the swing phase. After treadmill training reflexes were almost completely depressed during the swing phase. Conclusion: The present data show that treadmill training can induce changes in the modulation of short latency reflexes during gait. The complete suppression of the soleus H-reflex during the swing phase similar to healthy subjects could reflect an improvement towards a functionally more useful pattern. doi:10.1016/j.clinph.2006.11.116
Central motor conduction examined with the triple stimulation technique correlates with pyramidal tract dysfunction and disability in patients with multiple sclerosis—U. Hofstadt-van Oy, D. Hagenburger, C. Klawe, K. Schro¨der (Abt. fu¨ r Neurologie, Krankenhaus der Barmherzigen Bru¨ der, Trier, Germany) Inflammatory lesions and axonal degeneration of central motor conduction pathways result in gait disturbance and contributes particularly to increasing disability in patients with multiple sclerosis. With conventional transcranial magnetic stimulation central conduction times can be estimated but axonal damage or conduction block of motor pathways is less sensitively detected to correlate well with disability. The triple stimulation technique (TST) examines the corticospinal tract by magnetic stimulation of cortical motor areas followed by sequenced distal and proximal peripheral nerve electric stimulation. The originating potential is a result of the collison of the sequenced stimuli. Then the TSTpotential is compared with sequential stimulation of peripheral nerves alone. With the resulting amplitude ratio central conduction failure can be quantified by TST.
e48
Society Proceedings / Clinical Neurophysiology 118 (2007) e9–e116
Methods: Upper limb (to abductor digiti minimi muscle) and lower limb (to abductor hallucis muscle) TST was applied to 40 healthy volunteers to establish normal values. Sixty patients with relapsing remitting, secondary progressive and primary progressive multiple sclerosis underwent neurological examination including classification in the expanded disability status score (EDSS) according to Kurtzke and in the multiple sclerosis functional composite score (MSFC) including the nine hole peg test and timed walking distance to quantify upper und lower limb function. Results: The EDSS of patients varied between 0 and 8, 5. Central conduction failure quantified with TST correlated significantly with the functional system score for pyramidal tract dysfunction of the EDSS and the upper and lower limb motor tests of the MSCF. In higher EDSS ranges >3, 5 correlations were also proved. Conclusion: TST is a useful method to examine central conduction failure in different stages of disability in patients with Multiple sclerosis and correlates well with clinical deficits and disability scales reflecting motor involvement. doi:10.1016/j.clinph.2006.11.117
Interhemispheric interactions between M1 and PM during movement preparation—J. Hoppe, F. Hummel, H. Huber, D. Weiss, C. Gerloff (Neurologische Universita¨tsklinik, Tu¨bingen, Hertie Institut, fu¨r klinische Hirnforschung) Precise interhemispheric interactions constitute a necessary neural basis for bimanual and complex unimanual coordination, because integration of sensorimotor information of both hemispheres is required. At rest, the effect of interhemispheric interactions between homologous motor cortices (M1) is largely inhibitory (Gerloff et al., 1998. J Physiol (Lond) 510, 249–259). In the process of the generation of a movement, interhemispheric inhibition (IHI) between the M1 ipsilateral to the moving hand (iM1) and the M1 contralateral to the moving hand (cM1) turns into facilitation (‘release of IHI’) close to movement onset (Murase et al., 2004. Ann Neurol 55, 400–409). Anatomical studies suggest that callosal connections between homologous M1 are sparse. In fact, denser connectivity exists between premotor cortex (PM) and M1 of the opposite hemisphere (Rouiller et al., 1994. Exp Brain Res 102, 227–243). As an electrophysiological correlate of the latter, IHI has also been shown between PM and M1 (Mochizuki et al., 2004. J Physiol (Lond) 561, 331–338). In the present study, we set out to evaluate the movement-related dynamic modulation of IHI between the PM ipsilateral to the moving hand (iPM) and cM1. Specifically, we hypothesized that IHI from PM to cM1 is modulated earlier that IHI from iM1 to cM1, following a, in part, serial model of premotor and primary motor cortex activation (e.g., Gerloff et al., 1998. J. Clin. Neurophysiol. 15, 502–513). IHI between iPM and cM1 as well as iM1 and cM1 was studied in 14 healthy subjects during a simple reaction time task using with an established bi-hemispheric double-pulse TMS paradigm (Murase et al., 2004. Ann. Neurol. 55, 400–409). The conditioning stimulus was either applied over the right iPM (PM-IHI) or the right M1 (M1-IHI) ipsilateral to the moving right hand. The test stimulus was always applied over the left M1. At the earliest time point immediately after the go-signal comparable IHI was found with iPM and iM1 conditioning stimula-
tion. Over time, IHI was reduced close to movement onset in both conditions (ANOVA, factor TIME, p < 0.001). However there was a significant difference between M1-IHI and PM-IHI (ANOVA, p = 0.02) with an earlier reduction of IHI following PM stimulation compared with M1 stimulation. Whereas serial processing steps in the PM and M1 of the hemisphere contralateral to the moving hand are well accepted, the present data extends this view to interhemispheric interactions. doi:10.1016/j.clinph.2006.11.118
Context-related motor control implemented by modulation of cortical synchrony: A mechanism of successful context-related motor behavior—F. Hummel 1, F. Hummel 1, P. Sauseng 2, J. Hoppe 1, W. Klimesch 2, C. Gerloff 1 (1 Cortical Physiology Research Group, Department of Neurology and Hertie Institute for Clinical Brain Research, EberhardKarls University Tuebingen, Germany, 2 Institute of Psychology, University of Salzburg, Austria) Modulation of learned ‘‘motor programs’’ is the basis of context-adequate behavior, consisting of retrieval or non-retrieval (inhibition) of behavioral elements. Evidence was provided that focal activation/deactivation represents contextual modulation (Hummel, NIMG 2004). However, it remains open, how involved brain areas interact to implement retrieval and non-retrieval (inhibition). To address these questions phase coherence analysis was used to determine interactions between these brain areas. We evaluated EEG task-related phase coherence (TRPhCoh) and power (TRPow). Subjects trained finger movement sequences until they reached an overlearned level (MEM). The main experimental session consisted of 4 conditions: SEQUENCE (MEM vs. NOV [novel sequences of comparable complexity]) and CONTEXT (MOVE [subjects had to perform MEM or NOV] vs. NO-MOVE [subjects were asked not to perform]. The analysis was focused onto the upper a-band (10–13 Hz) (Hummel, Brain 2002). Task-related phase coherence: During MOVE performance of MEM and NOV revealed comparable TRPhCoh increases obtained in a network comprising prefrontal, sensorimotor and posterior parietal cortex. During NO-MOVE however, MEM showed significant decreases of TRPhCoh below baseline in the same network, which was not the case for NOV. Furthermore, a conjunction analysis between MOVE-MEM and NO-MOVEMEM revealed a network comprising prefrontal, posterior parietal and especially left sensorimotor cortex which showed enhanced coupling during MOVE and decoupling during NO-MOVE. Task-related power: During MOVE performance of MEM and NOV induced TRPow decreases obtained from sensorimotor cortex. During NO-MOVE performance of MEM and NOV induced TRPow increases. The present data suggest that modulation of cortical synchrony (coupling, decoupling) might be an underlying mechanism by which the brain implements successful context-related motor behavior. During retrieval of learned and novel motor acts activation of a fronto-centro-parietal network is implemented by enhanced phase coupling. The present data further indicate that deactivation during non-retrieval of learned motor acts is imple-