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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-g003: 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: The functional networks that showed a significant correlation between their temporal fluctuation and the condition where no learning occurred (i.e. ‘control condition’) are depicted in figure 3. It is important to note here, that all these areas showed decreased activity during the encoding phase and consequently might be interpreted as patterns of deactivation. In both genetic groups the common spatial pattern is similar, encompassing midline frontal, precuneus and lateral inferior parietal (see table 4). These brain regions have close anatomical correspondence with the well-characterized default-mode network (DMN) [41], [42].


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

Show All Figures
getmorefigures.php?uid=PMC3526481&req=5

pone-0051833-g003: 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: The functional networks that showed a significant correlation between their temporal fluctuation and the condition where no learning occurred (i.e. ‘control condition’) are depicted in figure 3. It is important to note here, that all these areas showed decreased activity during the encoding phase and consequently might be interpreted as patterns of deactivation. In both genetic groups the common spatial pattern is similar, encompassing midline frontal, precuneus and lateral inferior parietal (see table 4). These brain regions have close anatomical correspondence with the well-characterized default-mode network (DMN) [41], [42].

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