TY - JOUR
T1 - Impaired motor cortex plasticity in patients with Noonan syndrome
AU - Mainberger, Florian
AU - Zenker, Martin
AU - Jung, Nikolai H.
AU - Delvendahl, Igor
AU - Brandt, Antonia
AU - Freudenberg, Leonie
AU - Heinen, Florian
AU - Mall, Volker
N1 - Funding Information:
The authors would like to thank the patients and their parents for their participation. We would also like to thank U. Wößner for recruitment of patients with NS. This study was supported by a grant from Deutsche Forschungsgemeinschaft ( MA 3306/4-1 ).
PY - 2013/12
Y1 - 2013/12
N2 - Objective: Noonan syndrome (NS; OMIM 163950) is a developmental disorder caused by activating mutations in various components of the RAS-MAPK pathway. Recent in vitro studies demonstrated impairment of synaptic plasticity caused by RAS-MAPK pathway hyperactivity. Induction of synaptic plasticity critically depends on the level of attention. We therefore studied the induction of synaptic plasticity in patients with NS and healthy volunteers under different conditions of attention using transcranial magnetic stimulation. Methods: We investigated 10 patients with NS and healthy controls (HC) using paired associative stimulation (PAS) with different attention levels (unspecific, visual and electrical attention control). Changes in motor evoked potential (MEP) amplitudes were assessed immediately after as well as 30 and 60. min after PAS. Results: We demonstrated that MEP amplitudes of healthy controls significantly increased from 1.00. ±. 0.17 to 1.74. ±. 0.50. mV (p= 0.001), which was not seen in patients with Noonan-Syndrome (0.88. ±. 0.09 to 1.10. ±. 0.48. mV, p= 0.148) and there was a significant difference between both groups (p= 0.003) when using an unspecific attention control. Under specific electrical attention control, MEP amplitudes decreased significantly in patients with NS, whereas a visual attention focus diminished synaptic plasticity in healthy controls. Conclusion: Our study provides evidence that synaptic plasticity is impaired in patients with NS, which is probably a consequence of constitutive activity of the RAS-MAPK pathway. The induction of synaptic plasticity in these patients critically depends on attention. Significance: This is the first study that indicates reduced synaptic plasticity in patients with a RAS-pathway disorder. Our results may have direct implications for learning and memory strategies in patients with a RAS-pathway disorder.
AB - Objective: Noonan syndrome (NS; OMIM 163950) is a developmental disorder caused by activating mutations in various components of the RAS-MAPK pathway. Recent in vitro studies demonstrated impairment of synaptic plasticity caused by RAS-MAPK pathway hyperactivity. Induction of synaptic plasticity critically depends on the level of attention. We therefore studied the induction of synaptic plasticity in patients with NS and healthy volunteers under different conditions of attention using transcranial magnetic stimulation. Methods: We investigated 10 patients with NS and healthy controls (HC) using paired associative stimulation (PAS) with different attention levels (unspecific, visual and electrical attention control). Changes in motor evoked potential (MEP) amplitudes were assessed immediately after as well as 30 and 60. min after PAS. Results: We demonstrated that MEP amplitudes of healthy controls significantly increased from 1.00. ±. 0.17 to 1.74. ±. 0.50. mV (p= 0.001), which was not seen in patients with Noonan-Syndrome (0.88. ±. 0.09 to 1.10. ±. 0.48. mV, p= 0.148) and there was a significant difference between both groups (p= 0.003) when using an unspecific attention control. Under specific electrical attention control, MEP amplitudes decreased significantly in patients with NS, whereas a visual attention focus diminished synaptic plasticity in healthy controls. Conclusion: Our study provides evidence that synaptic plasticity is impaired in patients with NS, which is probably a consequence of constitutive activity of the RAS-MAPK pathway. The induction of synaptic plasticity in these patients critically depends on attention. Significance: This is the first study that indicates reduced synaptic plasticity in patients with a RAS-pathway disorder. Our results may have direct implications for learning and memory strategies in patients with a RAS-pathway disorder.
KW - Developmental disorder
KW - Long-term potentiation
KW - Paired associative stimulation (PAS)
KW - RAS-pathway
KW - Synaptic plasticity
KW - Transcranial magnetic stimulation (TMS)
UR - http://www.scopus.com/inward/record.url?scp=84887616818&partnerID=8YFLogxK
U2 - 10.1016/j.clinph.2013.04.343
DO - 10.1016/j.clinph.2013.04.343
M3 - Article
C2 - 23763990
AN - SCOPUS:84887616818
SN - 1388-2457
VL - 124
SP - 2439
EP - 2444
JO - Clinical Neurophysiology
JF - Clinical Neurophysiology
IS - 12
ER -