Ignite Creation Date:
2024-05-05 @ 11:41 AM
Last Modification Date:
2024-10-26 @ 9:11 AM
Study NCT ID:
NCT00102999
Status:
COMPLETED
Last Update Posted:
2017-07-02
First Post:
2005-02-04
Brief Title:
Brain Function in Focal Dystonia
Sponsor:
National Institute of Neurological Disorders and Stroke NINDS
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Impaired Motor Learning and LTPLTD-like Plasticity in Dystonia Are Associated With Abnormal Modulation of Cortical Excitability by Somatosensory Volleys
Status:
COMPLETED
Status Verified Date:
2009-01-22
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Objectives
The main objectives of this proposal are 1 to characterize motor learning abnormalities in patients with focal dystonia 2 to show using transcranial magnetic stimulation that this abnormal motor learning went together with an impaired modulation by somatosensory inputs of short and long-interval paired-pulse inhibitions sICI lICI and facilitations sICF ICF of MEPs ICIs and ICFs are thought to reflect activity of inhibitory and excitatory interneurons in the primary motor cortex M1 3 to show that abnormalities of long-term potentiation and long-term depression LTPLTD-like mechanisms tested using a paired associative stimulation PAS intervention thought to play a crucial role in learning are associated in dystonia with an abnormal modulation of ICIs and ICFs by somatosensory inputs
Study population
30 patients with a focal upper limb dystonia and 45 healthy volunteers will take part in the main study 7 patients with a focal upper limb dystonia and 12 healthy volunteers will take part in the control study
Design
In the main study subjects will complete 5 different sessions visit 1 clinical screening 1 hour visit PAS session 3 hours visit 3 a minimum of 7 days later motor learning session 3 hours visit 4 follow-up 24 hours later 1 hour and a half visit 5 follow-up 48 hours later 1 hour and a half During the PAS session they will receive 15 minutes of repeated paired stimulations transcranial magnetic stimulation -TMS- and peripheral stimulation thought to produce LTPLTD like phenomena in M1 During the motor learning sessions they will be asked to perform as fast as possible a metronome-paced 05 Hz pinch of their index finger and thumb They will have 3 blocks of motor practice during the motor learning session
Between each block of motor practice and before and after PAS while they rest subjects will receive paired-pulse transcranial magnetic stimulations TMS associated or not with peripheral nerve stimulation in order to assess interactions at M1 cortical level between somatosensory incoming volleys and intracortical inhibitory and excitatory interneurons
In the control study subjects will complete a unique session They will receive a PAS intervention Before and after the PAS intervention spinal excitability will be tested by the means of H reflexes evoked in wrist flexor muscles
Outcome measures
The behavioral effect of the motor training or of the PAS intervention will be assessed by measuring the mean peak acceleration MPA of thumb movement during the blocks of motor practice and the mean maximal peak force MPF between the index finger and thumb before and after the blocks of motor practice
The activity of different sets of intracortical interneurons short and long interval GABA related inhibitions sICI lICI intracortical glutamate-related facilitation ICF and short interval facilitation sICF can be tested using paired-pulse TMS paradigms The effect of learning or of PAS intervention on the interaction between somatosensory afferent input and intracortical processes will be assessed by comparing the amount of sICI lICI ICF and sICF when associated or not with a peripheral nerve stimulation median and ulnar nerve stimulation in a trained muscle flexor pollicis brevis FPB and a non-trained muscle abductor digiti minimi ADM at different times during and after the motor learning or the PAS intervention
The effect of PAS on spinal cord excitability will be assessed by comparing the size of the H reflex before and after PAS
The main objectives of this proposal are 1 to characterize motor learning abnormalities in patients with focal dystonia 2 to show using transcranial magnetic stimulation that this abnormal motor learning went together with an impaired modulation by somatosensory inputs of short and long-interval paired-pulse inhibitions sICI lICI and facilitations sICF ICF of MEPs ICIs and ICFs are thought to reflect activity of inhibitory and excitatory interneurons in the primary motor cortex M1 3 to show that abnormalities of long-term potentiation and long-term depression LTPLTD-like mechanisms tested using a paired associative stimulation PAS intervention thought to play a crucial role in learning are associated in dystonia with an abnormal modulation of ICIs and ICFs by somatosensory inputs
Study population
30 patients with a focal upper limb dystonia and 45 healthy volunteers will take part in the main study 7 patients with a focal upper limb dystonia and 12 healthy volunteers will take part in the control study
Design
In the main study subjects will complete 5 different sessions visit 1 clinical screening 1 hour visit PAS session 3 hours visit 3 a minimum of 7 days later motor learning session 3 hours visit 4 follow-up 24 hours later 1 hour and a half visit 5 follow-up 48 hours later 1 hour and a half During the PAS session they will receive 15 minutes of repeated paired stimulations transcranial magnetic stimulation -TMS- and peripheral stimulation thought to produce LTPLTD like phenomena in M1 During the motor learning sessions they will be asked to perform as fast as possible a metronome-paced 05 Hz pinch of their index finger and thumb They will have 3 blocks of motor practice during the motor learning session
Between each block of motor practice and before and after PAS while they rest subjects will receive paired-pulse transcranial magnetic stimulations TMS associated or not with peripheral nerve stimulation in order to assess interactions at M1 cortical level between somatosensory incoming volleys and intracortical inhibitory and excitatory interneurons
In the control study subjects will complete a unique session They will receive a PAS intervention Before and after the PAS intervention spinal excitability will be tested by the means of H reflexes evoked in wrist flexor muscles
Outcome measures
The behavioral effect of the motor training or of the PAS intervention will be assessed by measuring the mean peak acceleration MPA of thumb movement during the blocks of motor practice and the mean maximal peak force MPF between the index finger and thumb before and after the blocks of motor practice
The activity of different sets of intracortical interneurons short and long interval GABA related inhibitions sICI lICI intracortical glutamate-related facilitation ICF and short interval facilitation sICF can be tested using paired-pulse TMS paradigms The effect of learning or of PAS intervention on the interaction between somatosensory afferent input and intracortical processes will be assessed by comparing the amount of sICI lICI ICF and sICF when associated or not with a peripheral nerve stimulation median and ulnar nerve stimulation in a trained muscle flexor pollicis brevis FPB and a non-trained muscle abductor digiti minimi ADM at different times during and after the motor learning or the PAS intervention
The effect of PAS on spinal cord excitability will be assessed by comparing the size of the H reflex before and after PAS
Detailed Description:
OBJECTIVES
The main objectives of this proposal are 1 to characterize motor learning abnormalities in patients with focal dystonia 2 to show using transcranial magnetic stimulation that this abnormal motor learning went together with an impaired modulation by somatosensory inputs of short and long-interval paired-pulse inhibitions sICI lICI and facilitations sICF ICF of MEPs ICIs and ICFs are thought to reflect activity of inhibitory and excitatory interneurons in the primary motor cortex M1 3 to show that abnormalities of long-term potentiation and long-term depression LTPLTD-like mechanisms tested using a paired associative stimulation PAS intervention thought to play a crucial role in learning are associated in dystonia with an abnormal modulation of ICIs and ICFs by somatosensory inputs
STUDY POPULATION
30 patients with a focal upper limb dystonia and 45 healthy volunteers will take part in the main study
19 patients with a focal upper limb dystonia and 24 healthy volunteers will take part in the control study
DESIGN
In the main study subjects will complete 5 different sessions visit 1 clinical screening 1 hour visit 2 PAS session 3 hours visit 3 a minimum of 7 days later motor learning session 3 hours visit 4 follow-up 24 hours later 1hour and half visit 5 follow-up 48 hours later 1 hour and half During the PAS session they will receive 15 minutes of repeated paired stimulations transcranial magnetic stimulation -TMS- and peripheral stimulation thought to produce LTPLTD like phenomena in M1 During the motor learning sessions they will be asked to perform as fast as possible a metronome-paced 05 Hz pinch of their index finger and thumb They will have 3 blocks of motor practice during the motor learning session
Between each block of motor practice and before and after PAS while they rest subjects will receive paired-pulse transcranial magnetic stimulations TMS associated or not with peripheral nerve stimulation in order to assess interactions at M1 cortical level between somatosensory incoming volleys and intracortical inhibitory and excitatory interneurons
In the control studies subjects will complete a maximum of eight sessions They will receive a PAS intervention Before and after the PAS intervention spinal excitability will be tested by the means of H reflexes evoked in wrist flexors muscles H reflexes will be delivered alone or will be conditioned by cubital or radial nerve stimulation
OUTCOME MEASURES
The behavioral effect of the motor training or of the PAS intervention will be assessed by measuring the mean peak acceleration MPA of thumb movement during the blocks of motor practice and the mean maximal peak force MPF between the index finger and thumb before and after the blocks of motor practice
The activity of different sets of intracortical interneurons short and long interval GABA related inhibitions sICI lICI intracortical glutamate-related facilitation ICF and short interval facilitation sICF can be tested using paired-pulse TMS paradigms The effect of learning or of PAS intervention on the interaction between somatosensory afferent input and intracortical processes will be assessed by comparing the amount of sICI lICI ICF and sICF when associated or not with a peripheral nerve stimulation median and ulnar nerve stimulation in a trained muscle flexor pollicis brevis FPB and a non-trained muscle abductor digiti minimi ADM at different times during and after the motor learning or the PAS intervention
The effect of PAS on spinal cord excitability will be assessed by comparing the size of the H reflex alone the amounts of postactivation depression and those of presynaptic inhibition before and after PAS
The main objectives of this proposal are 1 to characterize motor learning abnormalities in patients with focal dystonia 2 to show using transcranial magnetic stimulation that this abnormal motor learning went together with an impaired modulation by somatosensory inputs of short and long-interval paired-pulse inhibitions sICI lICI and facilitations sICF ICF of MEPs ICIs and ICFs are thought to reflect activity of inhibitory and excitatory interneurons in the primary motor cortex M1 3 to show that abnormalities of long-term potentiation and long-term depression LTPLTD-like mechanisms tested using a paired associative stimulation PAS intervention thought to play a crucial role in learning are associated in dystonia with an abnormal modulation of ICIs and ICFs by somatosensory inputs
STUDY POPULATION
30 patients with a focal upper limb dystonia and 45 healthy volunteers will take part in the main study
19 patients with a focal upper limb dystonia and 24 healthy volunteers will take part in the control study
DESIGN
In the main study subjects will complete 5 different sessions visit 1 clinical screening 1 hour visit 2 PAS session 3 hours visit 3 a minimum of 7 days later motor learning session 3 hours visit 4 follow-up 24 hours later 1hour and half visit 5 follow-up 48 hours later 1 hour and half During the PAS session they will receive 15 minutes of repeated paired stimulations transcranial magnetic stimulation -TMS- and peripheral stimulation thought to produce LTPLTD like phenomena in M1 During the motor learning sessions they will be asked to perform as fast as possible a metronome-paced 05 Hz pinch of their index finger and thumb They will have 3 blocks of motor practice during the motor learning session
Between each block of motor practice and before and after PAS while they rest subjects will receive paired-pulse transcranial magnetic stimulations TMS associated or not with peripheral nerve stimulation in order to assess interactions at M1 cortical level between somatosensory incoming volleys and intracortical inhibitory and excitatory interneurons
In the control studies subjects will complete a maximum of eight sessions They will receive a PAS intervention Before and after the PAS intervention spinal excitability will be tested by the means of H reflexes evoked in wrist flexors muscles H reflexes will be delivered alone or will be conditioned by cubital or radial nerve stimulation
OUTCOME MEASURES
The behavioral effect of the motor training or of the PAS intervention will be assessed by measuring the mean peak acceleration MPA of thumb movement during the blocks of motor practice and the mean maximal peak force MPF between the index finger and thumb before and after the blocks of motor practice
The activity of different sets of intracortical interneurons short and long interval GABA related inhibitions sICI lICI intracortical glutamate-related facilitation ICF and short interval facilitation sICF can be tested using paired-pulse TMS paradigms The effect of learning or of PAS intervention on the interaction between somatosensory afferent input and intracortical processes will be assessed by comparing the amount of sICI lICI ICF and sICF when associated or not with a peripheral nerve stimulation median and ulnar nerve stimulation in a trained muscle flexor pollicis brevis FPB and a non-trained muscle abductor digiti minimi ADM at different times during and after the motor learning or the PAS intervention
The effect of PAS on spinal cord excitability will be assessed by comparing the size of the H reflex alone the amounts of postactivation depression and those of presynaptic inhibition before and after PAS
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 05-N-0094 | None | None | None |