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APOE status modulates the changes in network connectivity induced by brain stimulation in non-demented elders.

Peña-Gomez C, Solé-Padullés C, Clemente IC, Junqué C, Bargalló N, Bosch B, Molinuevo JL, Valls-Solé J, Pascual-Leone A, Bartrés-Faz D - PLoS ONE (2012)

Bottom Line: Baseline task performance was associated with activation of a network of brain regions in prefrontal, parietal, medial temporal and visual associative areas.However, after rTMS APOE ε4-carriers showed significant changes in brain network activation, expressing strikingly similar spatial configuration as the one observed in the non-carrier group prior to stimulation.Similarly, activity in areas of the default-mode network (DMN) was found in a single component among the ε4-non bearers, whereas among carriers it appeared disaggregated in three distinct spatiotemporal components that changed to an integrated single component after rTMS.Our findings demonstrate that genetic background play a fundamental role in the brain responses to focal insults, conditioning expression of distinct brain networks to sustain similar cognitive performance.

View Article: PubMed Central - PubMed

Affiliation: Department de Psiquiatria i Psicobiologia Clinica, Universitat de Barcelona, Barcelona, Catalonia, Spain.

ABSTRACT
Behavioral consequences of a brain insult represent an interaction between the injury and the capacity of the rest of the brain to adapt to it. We provide experimental support for the notion that genetic factors play a critical role in such adaptation. We induced a controlled brain disruption using repetitive transcranial magnetic stimulation (rTMS) and show that APOE status determines its impact on distributed brain networks as assessed by functional MRI (fMRI).Twenty non-demented elders exhibiting mild memory dysfunction underwent two fMRI studies during face-name encoding tasks (before and after rTMS). Baseline task performance was associated with activation of a network of brain regions in prefrontal, parietal, medial temporal and visual associative areas. APOE ε4 bearers exhibited this pattern in two separate independent components, whereas ε4-non carriers presented a single partially overlapping network. Following rTMS all subjects showed slight ameliorations in memory performance, regardless of APOE status. However, after rTMS APOE ε4-carriers showed significant changes in brain network activation, expressing strikingly similar spatial configuration as the one observed in the non-carrier group prior to stimulation. Similarly, activity in areas of the default-mode network (DMN) was found in a single component among the ε4-non bearers, whereas among carriers it appeared disaggregated in three distinct spatiotemporal components that changed to an integrated single component after rTMS.Our findings demonstrate that genetic background play a fundamental role in the brain responses to focal insults, conditioning expression of distinct brain networks to sustain similar cognitive performance.

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Related in: MedlinePlus

Effects of rTMS in the DMN present in deactivation task-related networks.While both groups exhibited increased temporal correlations between the timecourse of this network and rest condition after rTMS, its activity (intensity of the expression) clearly diverged. In the bar graphs it is shown that DMN activity decreased for ε4 non-carriers whereas increased for the ε4-carriers. Corr: Correlation values (r-Pearson) between the timecourse of each network and the ‘resting condition’. Intensity values are thresholded at z = 2.3. Coordinates are given in MNI (x = −4, z = 26). A.U = arbitrary units.
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pone-0051833-g004: Effects of rTMS in the DMN present in deactivation task-related networks.While both groups exhibited increased temporal correlations between the timecourse of this network and rest condition after rTMS, its activity (intensity of the expression) clearly diverged. In the bar graphs it is shown that DMN activity decreased for ε4 non-carriers whereas increased for the ε4-carriers. Corr: Correlation values (r-Pearson) between the timecourse of each network and the ‘resting condition’. Intensity values are thresholded at z = 2.3. Coordinates are given in MNI (x = −4, z = 26). A.U = arbitrary units.

Mentions: When looking at the intensity of deactivation by performing cross correlations between each network and a template of DMN (provided within the GIFT software), it was evident that among ε4-noncarriers the intensity of expression of the DMN was decreased subsequently to brain stimulation, whereas it was increased for APOE ε4 carriers. These results reflect enhanced connectivity between the components of the DMN areas after TMS in this group (see figure 4).


APOE status modulates the changes in network connectivity induced by brain stimulation in non-demented elders.

Peña-Gomez C, Solé-Padullés C, Clemente IC, Junqué C, Bargalló N, Bosch B, Molinuevo JL, Valls-Solé J, Pascual-Leone A, Bartrés-Faz D - PLoS ONE (2012)

Effects of rTMS in the DMN present in deactivation task-related networks.While both groups exhibited increased temporal correlations between the timecourse of this network and rest condition after rTMS, its activity (intensity of the expression) clearly diverged. In the bar graphs it is shown that DMN activity decreased for ε4 non-carriers whereas increased for the ε4-carriers. Corr: Correlation values (r-Pearson) between the timecourse of each network and the ‘resting condition’. Intensity values are thresholded at z = 2.3. Coordinates are given in MNI (x = −4, z = 26). A.U = arbitrary units.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3526481&req=5

pone-0051833-g004: Effects of rTMS in the DMN present in deactivation task-related networks.While both groups exhibited increased temporal correlations between the timecourse of this network and rest condition after rTMS, its activity (intensity of the expression) clearly diverged. In the bar graphs it is shown that DMN activity decreased for ε4 non-carriers whereas increased for the ε4-carriers. Corr: Correlation values (r-Pearson) between the timecourse of each network and the ‘resting condition’. Intensity values are thresholded at z = 2.3. Coordinates are given in MNI (x = −4, z = 26). A.U = arbitrary units.
Mentions: When looking at the intensity of deactivation by performing cross correlations between each network and a template of DMN (provided within the GIFT software), it was evident that among ε4-noncarriers the intensity of expression of the DMN was decreased subsequently to brain stimulation, whereas it was increased for APOE ε4 carriers. These results reflect enhanced connectivity between the components of the DMN areas after TMS in this group (see figure 4).

Bottom Line: Baseline task performance was associated with activation of a network of brain regions in prefrontal, parietal, medial temporal and visual associative areas.However, after rTMS APOE ε4-carriers showed significant changes in brain network activation, expressing strikingly similar spatial configuration as the one observed in the non-carrier group prior to stimulation.Similarly, activity in areas of the default-mode network (DMN) was found in a single component among the ε4-non bearers, whereas among carriers it appeared disaggregated in three distinct spatiotemporal components that changed to an integrated single component after rTMS.Our findings demonstrate that genetic background play a fundamental role in the brain responses to focal insults, conditioning expression of distinct brain networks to sustain similar cognitive performance.

View Article: PubMed Central - PubMed

Affiliation: Department de Psiquiatria i Psicobiologia Clinica, Universitat de Barcelona, Barcelona, Catalonia, Spain.

ABSTRACT
Behavioral consequences of a brain insult represent an interaction between the injury and the capacity of the rest of the brain to adapt to it. We provide experimental support for the notion that genetic factors play a critical role in such adaptation. We induced a controlled brain disruption using repetitive transcranial magnetic stimulation (rTMS) and show that APOE status determines its impact on distributed brain networks as assessed by functional MRI (fMRI).Twenty non-demented elders exhibiting mild memory dysfunction underwent two fMRI studies during face-name encoding tasks (before and after rTMS). Baseline task performance was associated with activation of a network of brain regions in prefrontal, parietal, medial temporal and visual associative areas. APOE ε4 bearers exhibited this pattern in two separate independent components, whereas ε4-non carriers presented a single partially overlapping network. Following rTMS all subjects showed slight ameliorations in memory performance, regardless of APOE status. However, after rTMS APOE ε4-carriers showed significant changes in brain network activation, expressing strikingly similar spatial configuration as the one observed in the non-carrier group prior to stimulation. Similarly, activity in areas of the default-mode network (DMN) was found in a single component among the ε4-non bearers, whereas among carriers it appeared disaggregated in three distinct spatiotemporal components that changed to an integrated single component after rTMS.Our findings demonstrate that genetic background play a fundamental role in the brain responses to focal insults, conditioning expression of distinct brain networks to sustain similar cognitive performance.

Show MeSH
Related in: MedlinePlus