- Email: [email protected]
Impairment of corticospinal excitability in normal pressure hydrocephalus
Brain Stimulation (2008) 1, 239-323
www.brainstimjrnl.com
Abstracts Imaging Poster Only 3
Modulation of [18F]CPFPX binding, a selective A1 adenosine receptor ligand, in the human brain – A study combining PET with neuronavigated repetitive transcranial magnetic stimulation
Sparing R1, Elmenhorst D2, Winz OH2, Minuzzi L2, Paus T3, Fink GR1, Bauer A2, 1Neurologie, Uniklinik Ko¨ln (Ko¨ln, DE); 2Institut fu¨r Neurowissenschaften und Biophysik (Juelich, DE); 3Brain & Body Centre (Nottingham, UK) Objective: This study examines the impact of excitatory (i.e., high frequency) repetitive transcranial magnetic stimulation (rTMS) on the binding of [18F]CPFPX, a selective A1 adenosine receptor (A1AR) ligand in the human brain, with PET. A1AR are widely distributed on cortical and subcortical neurons. The extracellular concentration of adenosine is amongst others coupled to cellular activity or metabolism. Method: In healthy subjects, we used a 140 min bolus plus constant infusion protocol. rTMS was applied in three blocks during the steady state phase of ligand delivery (50 to 140 min) inside the PET scanner. Each rTMS block (20 trains at 10 Hz, duration 1000 msec, intertrain interval 12 sec, intensity 90 % rMT) lasted 4 min. There was a resting period of 10 min following each block. Positioning of the coil over the medial dorsolateral prefrontal cortex (MDLPFC) according to probabilistic coordinates superimposed on individual normalized MRI was done by frameless stereotaxic neuronavigation. In addition, transmission scans were used to confirm the actual position of the coil and the stimulated area. The PET photo multipliers were shielded against the magnetic field of the TMS coil by a grounded metal tube. Plasma radioactivity concentration and metabolite analysis were performed in arterialised venous blood samples. Parametric total distribution volume (DVt) images were generated as tissue to plasma ratio and used for statistical analysis using SPM2. The 4 min blocks of stimulation were compared to 4 minframes before and after stimulation by collapsing the parts of the three strains into one bin using voxelwise paired t-test. Results: The main finding was a significantly reduced [18F]CPFPX binding during stimulation compared to baseline in the ipsilateral dorsal caudate nucleus. Based on this SPM results a region of interest analysis showed a relative DVt decrease of 24%. No changes were detected in the putamen, nucleus accumbens or the contralateral caudate. This decrease persisted to a lower degree over the 4 min after stimulation. Cortical binding at the site of stimulation was not affected. Conclusion: This is the first study to demonstrate a modulation of the binding of [18F]CPFPX by non-invasive brain stimulation in humans. It should be noted that further investigations are ongoing. We, nevertheless, believe that our results may lead to a better understanding of the physiological effects underlying TMS in the future.
Schabrun SM1, Stinear CM2, Byblow WD2, Ridding MC1, 1The University of Adelaide (Adelaide, AU); 2The University of Auckland (Auckland, NZ) Objective: Writer’s Cramp (WC) is a debilitating condition characterised by excessive muscle activity and an impaired ability to produce fractionated movements. Evidence suggests that maladaptive cortical plasticity and excessive representational overlap may be involved in the genesis of the abnormal motor patterns. Additionally, stereotypical afferent input produced during repetitive motor tasks may have an important role in driving representational overlap. Here we sought to establish whether a period of non-associative afferent stimulation (NAS) could reverse the excessive representational overlap in a group of WC patients and, importantly, examine the relationship between overlap and function. Method: Using transcranial magnetic stimulation (TMS), the representations of three hand muscles were mapped in 7 WC and 7 healthy participants. TMS mapping was carried out before and after a 1 hour period of NAS applied to the motor points of the right first dorsal interosseous (FDI) and right abductor pollicis brevis (APB). Participants performed a circle drawing task before and after NAS. Results: Prior to NAS the centres of gravity (CoGs) of the FDI and APB maps were situated significantly closer together (p 5 0.01) and the motor maps demonstrated greater overlap (p 5 0.03) in WC patients, who also demonstrated significant impairment in measures of drawing function (Coefficient of variation of velocity; p , 0.006). Following NAS the degree of overlap was significantly reduced (p 5 0.002), and the distance between the CoGs of the FDI and APB maps was increased (p 5 0.02) in WC patients. There was no significant change in the CoG or overlap measures for the control group following NAS. There was also a significant improvement in drawing performance in the WC patients following NAS. In addition, the increase in separation of the CoGs was positively correlated with the amount of functional improvement seen in the drawing task in WC patients (r 5 0.86, p 5 0.02). Conclusion: These novel findings provide further evidence for a link between increased representational overlap and the debilitating symptoms experienced by WC patients. Following a 1 hour period of NAS patients with the greatest increases in map separation experienced the greatest improvement in drawing function. These findings indicate that rehabilitation protocols which produce ordered and discrete cortical representations are likely to successfully alleviate the symptoms associated with WC.
Clinical Studies Poster Only 6
Impairment of corticospinal excitability in normal pressure hydrocephalus
Kaplan B, Chistyakov A, Hafner H, Zaaroor M, Rambam Medical Center (Haifa, IL)
Clinical Studies Poster Only 5
Separation of motor cortex representational maps is positively correlated with improvements in function in writer’s cramp patients
1935-861X/08/$ -see front matter Ó 2008 Elsevier Inc. All rights reserved.
Objective: Previous studies did not reveal any abnormalities in TMS evoked motor evoked potentials (MEPs) elicited from leg muscles in patients with gait disturbances associated with normal pressure hydrocephalus (NPH). However, to our knowledge effects of NPH on corticospinal excitability have not been investigated. The aim of the present study
240
Abstracts
was to evaluate changes in cortico-spinal excitability in patients with NPH in comparison with healthy subjects as well as patients with walking difficulties due to peripheral neuropathy. Methods: Fifteen patients with NPH were examined using single- and paired-pulse TMS techniques. MEPs were recorded bilaterally from the abductor hallucis brevis muscle. The MEP parameters assessed were the resting motor threshold (rMT), MEP/M-wave area ratio, central motor conduction time (CMCT), peripheral conduction time (PCT), intracortical facilitation (ICF) and short intracortical inhibition (SICI). Results: Significant reduction of the SICI associated with a significant decrease of the rMT was observed in patients with NPH compared to control subjects and patients with peripheral neuropathy. The CMCT and MEP/M-wave area ratio in NPH patients were unchanged. Conclusion: The results of this preliminary study suggest that NPH affects cortico-spinal excitability. The walking disturbances in patients with NPH could be, at least in part, related to the motor cortex disinhibition rather than impairment of central conduction along motor pathways.
Method: RTMS consisted of a triple-pulse burst (50 Hz) repeated every 200 ms for 2 s (10 bursts, 30 pulses); one kind of theta burst TMS (TBS) (Huang et al. 2005). The hemoglobin concentration changes were recorded at the right prefrontal cortex (PFC), premotor area (PM), primary hand motor area (M1) and primary sensory area (S1) during and after TBS over the left PM, M1 and S1 or sham stimulation in eight normal volunteers.
rTMS Poster Only 7
The movement induction in patients with spinal cord lesion after repetitive transcranial magnetic stimulation
Ma`lly J1, Dinya E2, 1Head of the Neurorehabilitation (Sopron, HU); 2 Medical Department (Budapest, HU) The basic therapy is the active and passive motion for the patients with spinal cord lesion (SCL). In spite of the intensive movement therapy about 20 % of patients with SCL could walk again. A few studies indicated that transcranial magnetic stimulation (rTMS) can decrease the spasticity and central pain in SCL. In this study we examined the movement induction in 15 patients with SCL, who were followed for a year. Main characteristics of the patients were: age: 26 6 7.1 yrs, duration of the disease: 2.8 6 4.0 yrs, thoracic lesion: n 5 13, cervical lesion: n 5 2, spastic paresis: n 5 10 hypoton paresis: n 5 5. There was no movement in the legs of 8 patients at the onset of the trial, 6 patients had slight movement in their hips in unloaded circumstances and 1 patient had restricted movement in her lying position. The single TMS at the 80 % of intensity of 2.3 Tover motor cortex could not evoke movement in legs in 9 patients. They were treated with 1 Hz rTMS for 7 days over the motor cortex, the spinal roots above the injury and the lumbar roots. The stimulation period was repeated from 4 to 7 times a year. The movements were tested with 0-3 pointes in the unloaded state. After 1 week treatment with rTMS movement started in the hips (p 5 0.0022). Extension of knee significantly differed from the 1st week after 1 month (p 5 0.0010). The knee flexion changed significantly after 9 months (p 5 0.0022). No movement was induced in the ankle. By the end of the year all of the patients could creep and 10 could take steps with walker while their knee extension was helped by a nurse. The higher number of treatment periods resulted more expressive improvement by the end of the year (sum of the score in hips: 4 times: 16.4 6 2.4; 7 times: 20.0 6 2.8). The development of movement was slow but progressive during the following year. It is encouraging that rTMS may help to recover movement after SCL.
rTMS Poster Only 8
Hemoglobin concentration changes in the contralateral hemisphere during and after theta burst stimulation of the human sensorimotor cortices
In addition, motor evoked potentials (MEPs) to TMS over the right M1 were recorded from the left first dorsal interosseous muscle 200 ms after the end of conditioning TBS over left S1. Results: TBS over PM induced a significant oxy-Hb decrease at the contralateral PM. TBS over M1 elicited a significant oxy-Hb decrease at the contralateral S1, and TBS over S1 significant oxy-Hb decreases at the contralateral M1 and S1.
MEPs to the right M1 stimulation were significantly suppressed by the conditioning TBS over the left S1. Conclusion: These results suggest that there are mainly inhibitory interactions between bilateral PMs and sensorimotor cortices in humans. In addition to the bilateral interaction between the primary motor cortices, the bilateral connections between the sensory and premotor cortices play important roles in smooth bimanual coordination.
rTMS
Mochizuki H1, Furubayashi T1, Hanajima R2, Terao Y2, Okabe S2, Ugawa Y1, 1Fukushima Medical University (Fukushima, JP); 2the University of Tokyo (Tokyo, JP)
Poster Only
Objective: Using near infrared spectroscopy (NIRS) and repetitive transcranial magnetic stimulation (rTMS), we studied interhemispheric interactions between bilateral motor and sensory cortices in humans.
Ho¨ppner J1, Domes G1, Herpertz SC1, Großheinrich N2, Herwig U3, Padberg F2, 1University of Rostock (Rostock, DE); 2Ludwig-Maximilian University (Mu¨nchen, DE); 3Psychiatric University Hospital (Zu¨rich, CH)
9
Reduction of psychomotor agitation in major depression by repetitive transcranial magnetic stimulation
www.brainstimjrnl.com
Abstracts Imaging Poster Only 3
Modulation of [18F]CPFPX binding, a selective A1 adenosine receptor ligand, in the human brain – A study combining PET with neuronavigated repetitive transcranial magnetic stimulation
Sparing R1, Elmenhorst D2, Winz OH2, Minuzzi L2, Paus T3, Fink GR1, Bauer A2, 1Neurologie, Uniklinik Ko¨ln (Ko¨ln, DE); 2Institut fu¨r Neurowissenschaften und Biophysik (Juelich, DE); 3Brain & Body Centre (Nottingham, UK) Objective: This study examines the impact of excitatory (i.e., high frequency) repetitive transcranial magnetic stimulation (rTMS) on the binding of [18F]CPFPX, a selective A1 adenosine receptor (A1AR) ligand in the human brain, with PET. A1AR are widely distributed on cortical and subcortical neurons. The extracellular concentration of adenosine is amongst others coupled to cellular activity or metabolism. Method: In healthy subjects, we used a 140 min bolus plus constant infusion protocol. rTMS was applied in three blocks during the steady state phase of ligand delivery (50 to 140 min) inside the PET scanner. Each rTMS block (20 trains at 10 Hz, duration 1000 msec, intertrain interval 12 sec, intensity 90 % rMT) lasted 4 min. There was a resting period of 10 min following each block. Positioning of the coil over the medial dorsolateral prefrontal cortex (MDLPFC) according to probabilistic coordinates superimposed on individual normalized MRI was done by frameless stereotaxic neuronavigation. In addition, transmission scans were used to confirm the actual position of the coil and the stimulated area. The PET photo multipliers were shielded against the magnetic field of the TMS coil by a grounded metal tube. Plasma radioactivity concentration and metabolite analysis were performed in arterialised venous blood samples. Parametric total distribution volume (DVt) images were generated as tissue to plasma ratio and used for statistical analysis using SPM2. The 4 min blocks of stimulation were compared to 4 minframes before and after stimulation by collapsing the parts of the three strains into one bin using voxelwise paired t-test. Results: The main finding was a significantly reduced [18F]CPFPX binding during stimulation compared to baseline in the ipsilateral dorsal caudate nucleus. Based on this SPM results a region of interest analysis showed a relative DVt decrease of 24%. No changes were detected in the putamen, nucleus accumbens or the contralateral caudate. This decrease persisted to a lower degree over the 4 min after stimulation. Cortical binding at the site of stimulation was not affected. Conclusion: This is the first study to demonstrate a modulation of the binding of [18F]CPFPX by non-invasive brain stimulation in humans. It should be noted that further investigations are ongoing. We, nevertheless, believe that our results may lead to a better understanding of the physiological effects underlying TMS in the future.
Schabrun SM1, Stinear CM2, Byblow WD2, Ridding MC1, 1The University of Adelaide (Adelaide, AU); 2The University of Auckland (Auckland, NZ) Objective: Writer’s Cramp (WC) is a debilitating condition characterised by excessive muscle activity and an impaired ability to produce fractionated movements. Evidence suggests that maladaptive cortical plasticity and excessive representational overlap may be involved in the genesis of the abnormal motor patterns. Additionally, stereotypical afferent input produced during repetitive motor tasks may have an important role in driving representational overlap. Here we sought to establish whether a period of non-associative afferent stimulation (NAS) could reverse the excessive representational overlap in a group of WC patients and, importantly, examine the relationship between overlap and function. Method: Using transcranial magnetic stimulation (TMS), the representations of three hand muscles were mapped in 7 WC and 7 healthy participants. TMS mapping was carried out before and after a 1 hour period of NAS applied to the motor points of the right first dorsal interosseous (FDI) and right abductor pollicis brevis (APB). Participants performed a circle drawing task before and after NAS. Results: Prior to NAS the centres of gravity (CoGs) of the FDI and APB maps were situated significantly closer together (p 5 0.01) and the motor maps demonstrated greater overlap (p 5 0.03) in WC patients, who also demonstrated significant impairment in measures of drawing function (Coefficient of variation of velocity; p , 0.006). Following NAS the degree of overlap was significantly reduced (p 5 0.002), and the distance between the CoGs of the FDI and APB maps was increased (p 5 0.02) in WC patients. There was no significant change in the CoG or overlap measures for the control group following NAS. There was also a significant improvement in drawing performance in the WC patients following NAS. In addition, the increase in separation of the CoGs was positively correlated with the amount of functional improvement seen in the drawing task in WC patients (r 5 0.86, p 5 0.02). Conclusion: These novel findings provide further evidence for a link between increased representational overlap and the debilitating symptoms experienced by WC patients. Following a 1 hour period of NAS patients with the greatest increases in map separation experienced the greatest improvement in drawing function. These findings indicate that rehabilitation protocols which produce ordered and discrete cortical representations are likely to successfully alleviate the symptoms associated with WC.
Clinical Studies Poster Only 6
Impairment of corticospinal excitability in normal pressure hydrocephalus
Kaplan B, Chistyakov A, Hafner H, Zaaroor M, Rambam Medical Center (Haifa, IL)
Clinical Studies Poster Only 5
Separation of motor cortex representational maps is positively correlated with improvements in function in writer’s cramp patients
1935-861X/08/$ -see front matter Ó 2008 Elsevier Inc. All rights reserved.
Objective: Previous studies did not reveal any abnormalities in TMS evoked motor evoked potentials (MEPs) elicited from leg muscles in patients with gait disturbances associated with normal pressure hydrocephalus (NPH). However, to our knowledge effects of NPH on corticospinal excitability have not been investigated. The aim of the present study
240
Abstracts
was to evaluate changes in cortico-spinal excitability in patients with NPH in comparison with healthy subjects as well as patients with walking difficulties due to peripheral neuropathy. Methods: Fifteen patients with NPH were examined using single- and paired-pulse TMS techniques. MEPs were recorded bilaterally from the abductor hallucis brevis muscle. The MEP parameters assessed were the resting motor threshold (rMT), MEP/M-wave area ratio, central motor conduction time (CMCT), peripheral conduction time (PCT), intracortical facilitation (ICF) and short intracortical inhibition (SICI). Results: Significant reduction of the SICI associated with a significant decrease of the rMT was observed in patients with NPH compared to control subjects and patients with peripheral neuropathy. The CMCT and MEP/M-wave area ratio in NPH patients were unchanged. Conclusion: The results of this preliminary study suggest that NPH affects cortico-spinal excitability. The walking disturbances in patients with NPH could be, at least in part, related to the motor cortex disinhibition rather than impairment of central conduction along motor pathways.
Method: RTMS consisted of a triple-pulse burst (50 Hz) repeated every 200 ms for 2 s (10 bursts, 30 pulses); one kind of theta burst TMS (TBS) (Huang et al. 2005). The hemoglobin concentration changes were recorded at the right prefrontal cortex (PFC), premotor area (PM), primary hand motor area (M1) and primary sensory area (S1) during and after TBS over the left PM, M1 and S1 or sham stimulation in eight normal volunteers.
rTMS Poster Only 7
The movement induction in patients with spinal cord lesion after repetitive transcranial magnetic stimulation
Ma`lly J1, Dinya E2, 1Head of the Neurorehabilitation (Sopron, HU); 2 Medical Department (Budapest, HU) The basic therapy is the active and passive motion for the patients with spinal cord lesion (SCL). In spite of the intensive movement therapy about 20 % of patients with SCL could walk again. A few studies indicated that transcranial magnetic stimulation (rTMS) can decrease the spasticity and central pain in SCL. In this study we examined the movement induction in 15 patients with SCL, who were followed for a year. Main characteristics of the patients were: age: 26 6 7.1 yrs, duration of the disease: 2.8 6 4.0 yrs, thoracic lesion: n 5 13, cervical lesion: n 5 2, spastic paresis: n 5 10 hypoton paresis: n 5 5. There was no movement in the legs of 8 patients at the onset of the trial, 6 patients had slight movement in their hips in unloaded circumstances and 1 patient had restricted movement in her lying position. The single TMS at the 80 % of intensity of 2.3 Tover motor cortex could not evoke movement in legs in 9 patients. They were treated with 1 Hz rTMS for 7 days over the motor cortex, the spinal roots above the injury and the lumbar roots. The stimulation period was repeated from 4 to 7 times a year. The movements were tested with 0-3 pointes in the unloaded state. After 1 week treatment with rTMS movement started in the hips (p 5 0.0022). Extension of knee significantly differed from the 1st week after 1 month (p 5 0.0010). The knee flexion changed significantly after 9 months (p 5 0.0022). No movement was induced in the ankle. By the end of the year all of the patients could creep and 10 could take steps with walker while their knee extension was helped by a nurse. The higher number of treatment periods resulted more expressive improvement by the end of the year (sum of the score in hips: 4 times: 16.4 6 2.4; 7 times: 20.0 6 2.8). The development of movement was slow but progressive during the following year. It is encouraging that rTMS may help to recover movement after SCL.
rTMS Poster Only 8
Hemoglobin concentration changes in the contralateral hemisphere during and after theta burst stimulation of the human sensorimotor cortices
In addition, motor evoked potentials (MEPs) to TMS over the right M1 were recorded from the left first dorsal interosseous muscle 200 ms after the end of conditioning TBS over left S1. Results: TBS over PM induced a significant oxy-Hb decrease at the contralateral PM. TBS over M1 elicited a significant oxy-Hb decrease at the contralateral S1, and TBS over S1 significant oxy-Hb decreases at the contralateral M1 and S1.
MEPs to the right M1 stimulation were significantly suppressed by the conditioning TBS over the left S1. Conclusion: These results suggest that there are mainly inhibitory interactions between bilateral PMs and sensorimotor cortices in humans. In addition to the bilateral interaction between the primary motor cortices, the bilateral connections between the sensory and premotor cortices play important roles in smooth bimanual coordination.
rTMS
Mochizuki H1, Furubayashi T1, Hanajima R2, Terao Y2, Okabe S2, Ugawa Y1, 1Fukushima Medical University (Fukushima, JP); 2the University of Tokyo (Tokyo, JP)
Poster Only
Objective: Using near infrared spectroscopy (NIRS) and repetitive transcranial magnetic stimulation (rTMS), we studied interhemispheric interactions between bilateral motor and sensory cortices in humans.
Ho¨ppner J1, Domes G1, Herpertz SC1, Großheinrich N2, Herwig U3, Padberg F2, 1University of Rostock (Rostock, DE); 2Ludwig-Maximilian University (Mu¨nchen, DE); 3Psychiatric University Hospital (Zu¨rich, CH)
9
Reduction of psychomotor agitation in major depression by repetitive transcranial magnetic stimulation