Impairment of Procedural Learning and Motor Intracortical Inhibition in Neurofibromatosis Type 1 Patients
Background: Cognitive difficulties are the most common neurological complications in neurofibromatosis type 1 (NF1) patients. Recent animal models proposed increased GABA-mediated inhibition as one underlying mechanism directly affecting the induction of long-term potentiation (LTP) and learning. In...
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| Format: | Article |
| Language: | English |
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Elsevier
2015-10-01
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| Series: | EBioMedicine |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396415301183 |
| _version_ | 1818945058682961920 |
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| author | Máximo Zimerman Maximilian J. Wessel Jan E. Timmermann Sofia Granström Christian Gerloff Victor F. Mautner Friedhelm C. Hummel |
| author_facet | Máximo Zimerman Maximilian J. Wessel Jan E. Timmermann Sofia Granström Christian Gerloff Victor F. Mautner Friedhelm C. Hummel |
| author_sort | Máximo Zimerman |
| collection | DOAJ |
| description | Background: Cognitive difficulties are the most common neurological complications in neurofibromatosis type 1 (NF1) patients. Recent animal models proposed increased GABA-mediated inhibition as one underlying mechanism directly affecting the induction of long-term potentiation (LTP) and learning. In most adult NF1 patients, apparent cognitive and attentional deficits, tumors affecting the nervous system and other confounding factors for neuroscientific studies are difficult to control for. Here we used a highly specific group of adult NF1 patients without cognitive or nervous system impairments. Such selected NF1 patients allowed us to address the following open questions: Is the learning process of acquiring a challenging motor skill impaired in NF1 patients? And is such an impairment in relation to differences in intracortical inhibition?
Methods: We used an established non-invasive, double-pulse transcranial magnetic stimulation (dp-TMS) paradigm to assess practice-related modulation of intracortical inhibition, possibly mediated by gamma-minobutyric acid (GABA)ergic-neurotransmission. This was done during an extended learning paradigm in a group of NF1 patients without any neuropsychological deficits, functioning normally in daily life and compared them to healthy age-matched controls.
Findings: NF1 patients experienced substantial decline in motor skill acquisition (F = 9.2, p = 0.008) over five-consecutives training days mediated through a selective reduction in the early acquisition (online) and the consolidation (offline) phase. Furthermore, there was a consistent decrease in task-related intracortical inhibition as a function of the magnitude of learning (T = 2.8, p = 0.014), especially evident after the early acquisition phase.
Interpretations: Collectively, the present results provide evidence that learning of a motor skill is impaired even in clinically intact NF1 patients based, at least partially, on a GABAergic-cortical dysfunctioning as suggested in previous animal work. |
| first_indexed | 2024-12-20T07:53:05Z |
| format | Article |
| id | doaj.art-e4843bc73655423d97741b48cc9cba7e |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-12-20T07:53:05Z |
| publishDate | 2015-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-e4843bc73655423d97741b48cc9cba7e2022-12-21T19:47:48ZengElsevierEBioMedicine2352-39642015-10-012101430143710.1016/j.ebiom.2015.08.036Impairment of Procedural Learning and Motor Intracortical Inhibition in Neurofibromatosis Type 1 PatientsMáximo Zimerman0Maximilian J. Wessel1Jan E. Timmermann2Sofia Granström3Christian Gerloff4Victor F. Mautner5Friedhelm C. Hummel6Brain Imaging and NeuroStimulation (BINS) Laboratory, Department of Neurology, University Medical Center Hamburg-Eppendorf, GermanyBrain Imaging and NeuroStimulation (BINS) Laboratory, Department of Neurology, University Medical Center Hamburg-Eppendorf, GermanyBrain Imaging and NeuroStimulation (BINS) Laboratory, Department of Neurology, University Medical Center Hamburg-Eppendorf, GermanySection for Neurofibromatosis, Department of Neurology, University Medical Center Hamburg-Eppendorf, GermanyBrain Imaging and NeuroStimulation (BINS) Laboratory, Department of Neurology, University Medical Center Hamburg-Eppendorf, GermanySection for Neurofibromatosis, Department of Neurology, University Medical Center Hamburg-Eppendorf, GermanyBrain Imaging and NeuroStimulation (BINS) Laboratory, Department of Neurology, University Medical Center Hamburg-Eppendorf, GermanyBackground: Cognitive difficulties are the most common neurological complications in neurofibromatosis type 1 (NF1) patients. Recent animal models proposed increased GABA-mediated inhibition as one underlying mechanism directly affecting the induction of long-term potentiation (LTP) and learning. In most adult NF1 patients, apparent cognitive and attentional deficits, tumors affecting the nervous system and other confounding factors for neuroscientific studies are difficult to control for. Here we used a highly specific group of adult NF1 patients without cognitive or nervous system impairments. Such selected NF1 patients allowed us to address the following open questions: Is the learning process of acquiring a challenging motor skill impaired in NF1 patients? And is such an impairment in relation to differences in intracortical inhibition? Methods: We used an established non-invasive, double-pulse transcranial magnetic stimulation (dp-TMS) paradigm to assess practice-related modulation of intracortical inhibition, possibly mediated by gamma-minobutyric acid (GABA)ergic-neurotransmission. This was done during an extended learning paradigm in a group of NF1 patients without any neuropsychological deficits, functioning normally in daily life and compared them to healthy age-matched controls. Findings: NF1 patients experienced substantial decline in motor skill acquisition (F = 9.2, p = 0.008) over five-consecutives training days mediated through a selective reduction in the early acquisition (online) and the consolidation (offline) phase. Furthermore, there was a consistent decrease in task-related intracortical inhibition as a function of the magnitude of learning (T = 2.8, p = 0.014), especially evident after the early acquisition phase. Interpretations: Collectively, the present results provide evidence that learning of a motor skill is impaired even in clinically intact NF1 patients based, at least partially, on a GABAergic-cortical dysfunctioning as suggested in previous animal work.http://www.sciencedirect.com/science/article/pii/S2352396415301183TMSNF1Motor LearningSICI |
| spellingShingle | Máximo Zimerman Maximilian J. Wessel Jan E. Timmermann Sofia Granström Christian Gerloff Victor F. Mautner Friedhelm C. Hummel Impairment of Procedural Learning and Motor Intracortical Inhibition in Neurofibromatosis Type 1 Patients EBioMedicine TMS NF1 Motor Learning SICI |
| title | Impairment of Procedural Learning and Motor Intracortical Inhibition in Neurofibromatosis Type 1 Patients |
| title_full | Impairment of Procedural Learning and Motor Intracortical Inhibition in Neurofibromatosis Type 1 Patients |
| title_fullStr | Impairment of Procedural Learning and Motor Intracortical Inhibition in Neurofibromatosis Type 1 Patients |
| title_full_unstemmed | Impairment of Procedural Learning and Motor Intracortical Inhibition in Neurofibromatosis Type 1 Patients |
| title_short | Impairment of Procedural Learning and Motor Intracortical Inhibition in Neurofibromatosis Type 1 Patients |
| title_sort | impairment of procedural learning and motor intracortical inhibition in neurofibromatosis type 1 patients |
| topic | TMS NF1 Motor Learning SICI |
| url | http://www.sciencedirect.com/science/article/pii/S2352396415301183 |
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