Person:
Bruña Fernández, Ricardo

First Name

Ricardo

Last Name

Bruña Fernández

URI

https://hdl.handle.net/20.500.14352/81051

Affiliation

Universidad Complutense de Madrid

Faculty / Institute

Medicina

Department

Radiología, Rehabilitación y Fisioterapia

Area

Radiología y Medicina Física

Identifiers

Full item page

Search Results

Now showing 1 - 10 of 10

Episodic memory dysfunction and hypersynchrony in brain functional networks in cognitively intact subjects and MCI: a study of 379 individuals
(Geroscience, 2022) Chino, Brenda; Cuesta Prieto, Pablo; Pacios García, Javier; De Frutos Lucas, Jaisalmer; Torres Simón, Lucía; Doval Moreno, Sandra; Marcos Dolado, Alberto; Bruña Fernández, Ricardo; Maestu Unturbe, Fernando
Delayed recall (DR) impairment is one of the most significant predictive factors in defining the progression to Alzheimer’s disease (AD). Changes in brain functional connectivity (FC) could accompany this decline in the DR performance even in a resting state condition from the preclinical stages to the diagnosis of AD itself, so the characterization of the relationship between the two phenomena has attracted increasing interest. Another aspect to contemplate is the potential moderator role of the APOE genotype in this association, considering the evidence about their implication for the disease. 379 subjects (118 mild cognitive impairment (MCI) and 261 cognitively intact (CI) individuals) underwent an extensive evaluation, including MEG recording. Applying cluster-based permutation test, we identified a cluster of differences in FC and studied which connections drove such an effect in DR. The moderation effect of APOE genotype between FC results and delayed recall was evaluated too. Higher FC in beta band in the right occipital region is associated with lower DR scores in both groups. A significant anteroposterior link emerged in the seed-based analysis with higher values in MCI. Moreover, APOE genotype appeared as a moderator between beta FC and DR performance only in the CI group. An increased beta FC in the anteroposterior brain region appears to be associated with lower memory performance in MCI. This finding could help discriminate the pattern of the progression of healthy aging to MCI and the relation between resting state and memory performance.
Hypersynchronization in mild cognitive impairment: the ‘X’ model
(Brain, 2019) Pusil Arce, Sandra Angélica; López García, María Eugenia; Cuesta Prieto, Pablo; Bruña Fernández, Ricardo; Pereda, Ernesto; Maestu Unturbe, Fernando
Hypersynchronization has been proposed as a synaptic dysfunction biomarker in the Alzheimer's disease continuum, reflecting the alteration of the excitation/inhibition balance. While animal models have verified this idea extensively, there is still no clear evidence in humans. Here we test this hypothesis, evaluating the risk of conversion from mild cognitive impairment (MCI) to Alzheimer's disease in a longitudinal study. We compared the functional resting state eyes-closed magnetoencephalographic networks of 54 patients with MCI who were followed-up every 6 months. According to their clinical outcome, they were split into: (i) the 'progressive' MCI (n = 27) group; and (ii) the 'stable' MCI group (n = 27). They did not differ in gender or educational level. For all participants, two magnetoencephalographic recordings were acquired. Functional connectivity was evaluated using the phase locking value. To extract the functional connectivity network with significant changes between both magnetoencephalographic recordings, we evaluated the functional connectivity ratio, defined as functional connectivity post-/pre-condition, in a network-based statistical model with an ANCOVA test with age as covariate. Two significant networks were found in the theta and beta bands, involving fronto-temporal and fronto-occipital connections, and showing a diminished functional connectivity ratio in the progressive MCI group. These topologies were then evaluated at each condition showing that at baseline, patients with progressive MCI showed higher synchronization than patients with stable MCI, while in the post-condition this pattern was reversed. These results may be influenced by two main factors in the post-condition: the increased synchrony in the stable MCI patients and the network failure in the progressive MCI patients. These findings may be explained as an 'X' form model where the hypersynchrony predicts conversion, leading subsequently to a network breakdown in progressive MCI. Patients with stable MCI showed an opposite phenomenon, which could indicate that they were a step beyond in the Alzheimer's disease continuum. This model would be able to predict the risk for the conversion to dementia in MCI patients.
Influence of the APOE ε4 allele and mild cognitive impairment diagnosis in the disruption of the MEG resting state functional connectivity in sources space
(Journal of Alzheimer's Disease, 2015) Cuesta Prieto, Pablo; Garcés, Pilar; Castellanos, Nazareth P; López García, María Eugenia; Aurtenetxe, Sara; Bajo, Ricardo; Pineda-Pardo, José Angel; Bruña Fernández, Ricardo; Marín, Antonio García; Delgado Losada, María Luisa; Barabash Bustelo, Ana; Ancín, Inés; Cabranes Díaz, José Antonio; Fernández Lucas, Alberto Amable; del Pozo, Francisco; Sancho Ruiz, Miguel; Marcos Dolado, Alberto; Nakamura, Akinori; Maestu Unturbe, Fernando
The apolipoprotein E (APOE) ε4 allele constitutes the major genetic risk for the development of late onset Alzheimer's disease (AD). However, its influence on the neurodegeneration that occurs in early AD remains unresolved. In this study, the resting state magnetoencephalography(MEG) recordings were obtained from 27 aged healthy controls and 36 mild cognitive impairment (MCI) patients. All participants were divided into carriers and non-carriers of the ε4 allele. We have calculated the functional connectivity (FC) in the source space along brain regions estimated using the Harvard-Oxford atlas and in the classical bands. Then, a two way ANOVA analysis (diagnosis and APOE) was performed in each frequency band. The diagnosis effect consisted of a diminished FC within the high frequency bands in the MCI patients, affecting medial temporal and parietal regions. The APOE effect produced a decreased long range FC in delta band in ε4 carriers. Finally, the interaction effect showed that the FC pattern of the right frontal-temporal region could be reflecting a compensatory/disruption process within the ε4 allele carriers. Several of these results correlated with cognitive decline and neuropsychological performance. The present study characterizes how the APOE ε4 allele and MCI status affect the brain's functional organization by analyzing the FC patterns in MEG resting state in the sources space. Therefore a combination of genetic, neuropsychological, and neurophysiological information might help to detect MCI patients at higher risk of conversion to AD and asymptomatic subjects at higher risk of developing a manifest cognitive deterioration.
Age and APOE genotype affect the relationship between objectively measured physical activity and power in the alpha band, a marker of brain disease
(Alzheimer's Research & Therapy, 2020) De Frutos Lucas, Jaisalmer; Cuesta Prieto, Pablo; Ramírez Toraño, Federico; Nebreda Pérez, Alberto; Cuadrado Soto, Esther; Peral Suárez, África; López Sanz, David; Bruña Fernández, Ricardo; Marcos-de Pedro, Silvia; Delgado Losada, María Luisa; López Sobaler, Ana María; Rodríguez Rojo, Inmaculada Concepción; Barabash Bustelo, Ana; Serrano Rodríguez, Juan Manuel; Laws, Simon M.; Marcos Dolado, Alberto; López Sánchez, Ramón; Brown, Belinda M.; Maestu Unturbe, Fernando
BACKGROUND: Electrophysiological studies show that reductions in power within the alpha band are associated with the Alzheimer’s disease (AD) continuum. Physical activity (PA) is a protective factor that has proved to reduce AD risk and pathological brain burden. Previous research has confirmed that exercise increases power in the alpha range. However, little is known regarding whether other non-modifiable risk factors for AD, such as increased age or APOE ε4 carriage, alter the association between PA and power in the alpha band. METHODS: The relationship between PA and alpha band power was examined in a sample of 113 healthy adults using magnetoencephalography. Additionally, we explored whether ε4 carriage and age modulate this association. The correlations between alpha power and gray matter volumes and cognition were also investigated. RESULTS: We detected a parieto-occipital cluster in which PA positively correlated with alpha power. The association between PA and alpha power remained following stratification of the cohort by genotype. Younger and older adults were investigated separately, and only younger adults exhibited a positive relationship between PA and alpha power. Interestingly, when four groups were created based on age (younger-older adult) and APOE (E3/E3-E3/E4), only younger E3/E3 (least predicted risk) and older E3/E4 (greatest predicted risk) had associations between greater alpha power and higher PA. Among older E3/E4, greater alpha power in these regions was associated with improved memory and preserved brain structure. CONCLUSION: PA could protect against the slowing of brain activity that characterizes the AD continuum, where it is of benefit for all individuals, especially E3/E4 older adults.
BDNF Val66Met polymorphism and gamma band disruption in resting state brain functional connectivity: A magnetoencephalography study in cognitively intact older females
(Frontiers in Neuroscience, 2018) Rodríguez Rojo, Inmaculada Concepción; Cuesta Prieto, Pablo; López García, María Eugenia; De Frutos Lucas, Jaisalmer; Bruña Fernández, Ricardo; Pereda de Pablo, Ernesto; Barabash Bustelo, Ana; Montejo, Pedro; Montenegro Peña, María Mercedes; Marcos Dolado, Alberto; López-Higes, Ramón; Fernández Lucas, Alberto Amable; Maestu Unturbe, Fernando
The pathophysiological processes undermining brain functioning decades before the onset of the clinical symptoms associated with dementia are still not well understood. Several heritability studies have reported that the Brain Derived Neurotrophic Factor (BDNF) Val66Met genetic polymorphism could contribute to the acceleration of cognitive decline in aging. This mutation may affect brain functional connectivity (FC), especially in those who are carriers of the BDNF Met allele. The aim of this work was to explore the influence of the BDNF Val66Met polymorphism in whole brain eyes-closed, resting-state magnetoencephalography (MEG) FC in a sample of 36 cognitively intact (CI) older females. All of them were ε3ε3 homozygotes for the apolipoprotein E (APOE) gene and were divided into two subgroups according to the presence of the Met allele: Val/Met group (n = 16) and Val/Val group (n = 20). They did not differ in age, years of education, Mini-Mental State Examination scores, or normalized hippocampal volumes. Our results showed reduced antero-posterior gamma band FC within the Val/Met genetic risk group, which may be caused by a GABAergic network impairment. Despite the lack of cognitive decline, these results might suggest a selective brain network vulnerability due to the carriage of the BDNF Met allele, which is linked to a potential progression to dementia. This neurophysiological signature, as tracked with MEG FC, indicates that age-related brain functioning changes could be mediated by the influence of particular genetic risk factors.
How to Build a Functional Connectomic Biomarker for Mild Cognitive Impairment From Source Reconstructed MEG Resting-State Activity: The Combination of ROI Representation and Connectivity Estimator Matters
(Frontiers in Neuroscience, 2018) López García, María Eugenia; Bruña Fernández, Ricardo; Cuesta Prieto, Pablo; Marcos Dolado, Alberto; Maestu Unturbe, Fernando
Our work aimed to demonstrate the combination of machine learning and graph theory for the designing of a connectomic biomarker for mild cognitive impairment (MCI) subjects using eyes-closed neuromagnetic recordings. The whole analysis based on source-reconstructed neuromagnetic activity. As ROI representation, we employed the principal component analysis (PCA) and centroid approaches. As representative bi-variate connectivity estimators for the estimation of intra and cross-frequency interactions, we adopted the phase locking value (PLV), the imaginary part (iPLV) and the correlation of the envelope (CorrEnv). Both intra and cross-frequency interactions (CFC) have been estimated with the three connectivity estimators within the seven frequency bands (intra-frequency) and in pairs (CFC), correspondingly. We demonstrated how different versions of functional connectivity graphs single-layer (SL-FCG) and multi-layer (ML-FCG) can give us a different view of the functional interactions across the brain areas. Finally, we applied machine learning techniques with main scope to build a reliable connectomic biomarker by analyzing both SL-FCG and ML-FCG in two different options: as a whole unit using a tensorial extraction algorithm and as single pair-wise coupling estimations. We concluded that edge-weighed feature selection strategy outperformed the tensorial treatment of SL-FCG and ML-FCG. The highest classification performance was obtained with the centroid ROI representation and edge-weighted analysis of the SL-FCG reaching the 98% for the CorrEnv in α1:α2 and 94% for the iPLV in α2. Classification performance based on the multi-layer participation coefficient, a multiplexity index reached 52% for iPLV and 52% for CorrEnv. Selected functional connections that build the multivariate connectomic biomarker in the edge-weighted scenario are located in default-mode, fronto-parietal, and cingulo-opercular network. Our analysis supports the notion of analyzing FCG simultaneously in intra and cross-frequency whole brain interactions with various connectivity estimators in beamformed recordings.
Searching for Primary Predictors of Conversion from Mild Cognitive Impairment to Alzheimer’s Disease: A Multivariate Follow-Up Study
(Journal of Alzheimer's Disease, 2016) López García, María Eugenia; Turrero Nogués, Agustín; Cuesta Prieto, Pablo; López Sanz, David; Bruña Fernández, Ricardo; Marcos Dolado, Alberto; Gil Gregorio, Pedro; Yus, Miguel; Barabash Bustelo, Ana; Cabranes Díaz, José Antonio; Maestu Unturbe, Fernando; Fernández Lucas, Alberto Amable
Recent proposals of diagnostic criteria within the healthy aging-Alzheimer’s disease (AD) continuum stressed the role of biomarker information. More importantly, such information might be critical to predict those mild cognitive impairment (MCI) patients at a higher risk of conversion to AD. Usually, follow-up studies utilize a reduced number of potential markers although the conversion phenomenon may be deemed as multifactorial in essence. In addition, not only biological but also cognitive markers may play an important role. Considering this background, we investigated the role of cognitive reserve, cognitive performance in neuropsychological testing, hippocampal volumes, APOE genotype, and magnetoencephalography power sources to predict the conversion to AD in a sample of 33 MCI patients. MCIs were followed up during a 2-year period and divided into two subgroups according to their outcome: The “stable” MCI group (sMCI, 21 subjects) and the “progressive” MCI group (pMCI, 12 subjects). Baseline multifactorial information was submitted to a hierarchical logistic regression analysis to build a predictive model of conversion to AD. Results indicated that the combination of left hippocampal volume, occipital cortex theta power, and clock drawing copy subtest scores predicted conversion to AD with a 100% of sensitivity and 94.7% of specificity. According to these results it might be suggested that anatomical, cognitive, and neurophysiological markers may be considered as “first order” predictors of progression to AD, while APOE or cognitive reserve proxies might play a more secondary role.
Enhancement of posterior brain functional networks in bilingual older adults
(Bilingualism: Language and Cognition, 2019) De Frutos Lucas, Jaisalmer; López Sanz, David; Cuesta Prieto, Pablo; Bruña Fernández, Ricardo; Fuente, Sofía de la; Serrano Martínez, Noelia; López García, María Eugenia; Delgado Losada, María Luisa; López Sánchez, Ramón; Marcos Dolado, Alberto; Maestu Unturbe, Fernando
Bilingualism has been said to improve cognition and even delay the onset of Alzheimer's disease (AD). This research aimed to investigate whether bilingualism leaves a neurophysiological trace even when people are highly educated. We expected bilinguals to present better preserved brain functional networks, which could be a trace of higher cognitive reserve. With this purpose, we conducted a magnetoencephalographic study with a group of healthy older adults. We estimated functional connectivity using phase-locking value and found five clusters in parieto-occipital regions in which bilinguals exhibited greater functional connectivity than monolinguals. These clusters included brain regions typically implicated in language processing. Furthermore, these functional changes correlated with caudate volumes (a key region in language shifting and control) in the bilingual sample. Interestingly, decreased Functional Connectivity between posterior brain regions had already been identified as an indicator of aging/preclinical AD but, according to our study, bilingualism seems to exert the opposite effect.
The relationship between physical activity, apolipoprotein E ε4 carriage, and brain health
(Alzheimer's Research & Therapy, 2020) De Frutos Lucas, Jaisalmer; Cuesta Prieto, Pablo; López Sanz, David; Peral Suárez, África; Cuadrado Soto, Esther; Ramírez Toraño, Federico; Brown, Belinda M.; Serrano, Juan M.; Laws, Simon M.; Rodríguez Rojo, Inmaculada Concepción; Verdejo Román, Juan; Bruña Fernández, Ricardo; Delgado Losada, María Luisa; Barabash Bustelo, Ana; López Sobaler, Ana María; López Sánchez, Ramón; Marcos Dolado, Alberto; Maestu Unturbe, Fernando
Background: Neuronal hyperexcitability and hypersynchrony have been described as key features of neurophysiological dysfunctions in the Alzheimer’s disease (AD) continuum. Conversely, physical activity (PA) has been associated with improved brain health and reduced AD risk. However, there is controversy regarding whether AD genetic risk (in terms of APOE ε4 carriage) modulates these relationships. The utilization of multiple outcome measures within one sample may strengthen our understanding of this complex phenomenon. Method: The relationship between PA and functional connectivity (FC) was examined in a sample of 107 healthy older adults using magnetoencephalography. Additionally, we explored whether ε4 carriage modulates this association. The correlation between FC and brain structural integrity, cognition, and mood was also investigated. Results: A relationship between higher PA and decreased FC (hyposynchrony) in the left temporal lobe was observed among all individuals (across the whole sample, in ε4 carriers, and in ε4 non-carriers), but its effects manifest differently according to genetic risk. In ε4 carriers, we report an association between this region-specific FC profile and preserved brain structure (greater gray matter volumes and higher integrity of white matter tracts). In this group, decreased FC also correlated with reduced anxiety levels. In ε4 non-carriers, this profile is associated with improved cognition (working and episodic memory). Conclusions: PA could mitigate the increase in FC (hypersynchronization) that characterizes preclinical AD, being beneficial for all individuals, especially ε4 carriers.
An individual data-driven virtual resection model based on epileptic network dynamics in children with intractable epilepsy: a magnetoencephalography interictal activity application
(Brain Communications, 2023) Cuesta Prieto, Pablo; Bruña Fernández, Ricardo; Shah, Ekta; Laohathai, Christopher; Garcia-Tarodo, Stephanie; Funke, Michael; Von Allmen, Gretchen; Maestu Unturbe, Fernando
Epilepsy surgery continues to be a recommended treatment for intractable (medication-resistant) epilepsy; however, 30–70% of epilepsy surgery patients can continue to have seizures. Surgical failures are often associated with incomplete resection or inaccurate localization of the epileptogenic zone. This retrospective study aims to improve surgical outcome through in silico testing of surgical hypotheses through a personalized computational neurosurgery model created from individualized patient’s magnetoencephalography recording and MRI. The framework assesses the extent of the epileptic network and evaluates underlying spike dynamics, resulting in identification of one single brain volume as a candidate for resection. Dynamic-locked networks were utilized for virtual cortical resection. This in silico protocol was tested in a cohort of 24 paediatric patients with focal drug-resistant epilepsy who underwent epilepsy surgery. Of 24 patients who were included in the analysis, 79% (19 of 24) of the models agreed with the patient's clinical surgery outcome and 21% (5 of 24) were considered as model failures (accuracy 0.79, sensitivity 0.77, specificity 0.82). Patients with unsuccessful surgery outcome typically showed a model cluster outside of the resected cavity, while those with successful surgery showed the cluster model within the cavity. Two of the model failures showed the cluster in the vicinity of the resected tissue and either a functional disconnection or lack of precision of the magnetoencephalography–MRI overlapping could explain the results. Two other cases were seizure free for 1 year but developed late recurrence. This is the first study that provides in silico personalized protocol for epilepsy surgery planning using magnetoencephalography spike network analysis. This model could provide complementary information to the traditional pre-surgical assessment methods and increase the proportion of patients achieving seizure-free outcome from surgery.