TMS-EEG signatures of GABAergic neurotransmission in the human cortex.

Combining transcranial magnetic stimulation (TMS) and electroencephalography (EEG) constitutes a powerful tool to directly assess human cortical excitability and connectivity. TMS of the primary motor cortex elicits a sequence of TMS-evoked EEG potentials (TEPs). It is thought that inhibitory neurotransmission through GABA-A receptors (GABAAR) modulates early TEPs (<50 ms after TMS), whereas GABA-B receptors (GABABR) play a role for later TEPs (at ∼100 ms after TMS). However, the physiological underpinnings of TEPs have not been clearly elucidated yet. Here, we studied the role of GABAA/B-ergic neurotransmission for TEPs in healthy subjects using a pharmaco-TMS-EEG approach. In Experiment 1, we tested the effects of a single oral dose of alprazolam (a classical benzodiazepine acting as allosteric-positive modulator at α1, α2, α3, and α5 subunit-containing GABAARs) and zolpidem (a positive modulator mainly at the α1 GABAAR) in a double-blind, placebo-controlled, crossover study. In Experiment 2, we tested the influence of baclofen (a GABABR agonist) and diazepam (a classical benzodiazepine) versus placebo on TEPs. Alprazolam and diazepam increased the amplitude of the negative potential at 45 ms after stimulation (N45) and decreased the negative component at 100 ms (N100), whereas zolpidem increased the N45 only. In contrast, baclofen specifically increased the N100 amplitude. These results provide strong evidence that the N45 represents activity of α1-subunit-containing GABAARs, whereas the N100 represents activity of GABABRs. Findings open a novel window of opportunity to study alteration of GABAA-/GABAB-related inhibition in disorders, such as epilepsy or schizophrenia.

Source-reconstruction of event-related fields reveals hyperfunction and hypofunction of cortical circuits in antipsychotic-naive, first-episode schizophrenia patients during Mooney face processing.

Schizophrenia is characterized by dysfunctions in neural circuits that can be investigated with electrophysiological methods, such as EEG and MEG. In the present human study, we examined event-related fields (ERFs), in a sample of medication-naive, first-episode schizophrenia (FE-ScZ) patients (n = 14) and healthy control participants (n = 17) during perception of Mooney faces to investigate the integrity of neuromagnetic responses and their experience-dependent modification. ERF responses were analyzed for M100, M170, and M250 components at the sensor and source levels. In addition, we analyzed peak latency and adaptation effects due to stimulus repetition. FE-ScZ patients were characterized by significantly impaired sensory processing, as indicated by a reduced discrimination index (A'). At the sensor level, M100 and M170 responses in FE-ScZ were within the normal range, whereas the M250 response was impaired. However, source localization revealed widespread elevated activity for M100 and M170 in FE-ScZ and delayed peak latencies for the M100 and M250 responses. In addition, M170 source activity in FE-ScZ was not modulated by stimulus repetitions. The present findings suggest that neural circuits in FE-ScZ may be characterized by a disturbed balance between excitation and inhibition that could lead to a failure to gate information flow and abnormal spreading of activity, which is compatible with dysfunctional glutamatergic neurotransmission.

Alterations in cortical thickness development in preterm-born individuals: Implications for high-order cognitive functions.

Very preterm birth (gestational age <33 weeks) is associated with alterations in cortical thickness and with neuropsychological/behavioural impairments. Here we studied cortical thickness in very preterm born individuals and controls in mid-adolescence (mean age 15 years) and beginning of adulthood (mean age 20 years), as well as longitudinal changes between the two time points. Using univariate approaches, we showed both increases and decreases in cortical thickness in very preterm born individuals compared to controls. Specifically (1) very preterm born adolescents displayed extensive areas of greater cortical thickness, especially in occipitotemporal and prefrontal cortices, differences which decreased substantially by early adulthood; (2) at both time points, very preterm-born participants showed smaller cortical thickness, especially in parahippocampal and insular regions. We then employed a multivariate approach (support vector machine) to study spatially discriminating features between the two groups, which achieved a mean accuracy of 86.5%. The spatially distributed regions in which cortical thickness best discriminated between the groups (top 5%) included temporal, occipitotemporal, parietal and prefrontal cortices. Within these spatially distributed regions (top 1%), longitudinal changes in cortical thickness in left temporal pole, right occipitotemporal gyrus and left superior parietal lobe were significantly associated with scores on language-based tests of executive function. These results describe alterations in cortical thickness development in preterm-born individuals in their second decade of life, with implications for high-order cognitive processing.

Differential contribution of hippocampal circuits to appetitive and consummatory behaviors during operant conditioning of behaving mice.

Operant conditioning is a type of associative learning involving different and complex sensorimotor and cognitive processes. Because the hippocampus has been related to some motor and cognitive functions involved in this type of learning (such as object recognition, spatial orientation, and associative learning tasks), we decided to study in behaving mice the putative changes in strength taking place at the hippocampal CA3-CA1 synapses during the acquisition and performance of an operant conditioning task. Mice were chronically implanted with stimulating electrodes in the Schaffer collaterals and with recording electrodes in the hippocampal CA1 area and trained to an operant task using a fixed-ratio (1:1) schedule. We recorded the field EPSPs (fEPSPs) evoked at the CA3-CA1 synapse during the performance of appetitive (going to the lever, lever press) and consummatory (going to the feeder, eating) behaviors. In addition, we recorded the local field potential activity of the CA1 area during similar behavioral displays. fEPSPs evoked at the CA3-CA1 synapse presented larger amplitudes for appetitive than for consummatory behaviors. This differential change in synaptic strength took place in relation to the learning process, depending mainly on the moment in which mice reached the selected criterion. Thus, selective changes in CA3-CA1 synaptic strength were dependent on both the behavior display and the learning stage. In addition, significant changes in theta band power peaks and their corresponding discrete frequencies were noticed during these behaviors across the sequence of events characterizing this type of associative learning but not during the acquisition process.

Characterization of GABAB-receptor mediated neurotransmission in the human cortex by paired-pulse TMS-EEG.

GABAB-receptor (GABABR) mediated inhibition is important in regulating neuronal excitability. The paired-pulse transcranial magnetic stimulation (TMS) protocol of long-interval intracortical inhibition (LICI) likely reflects this GABABergic inhibition. However, this view is based on indirect evidence from electromyographic (EMG) studies. Here we combined paired-pulse TMS with simultaneous electroencephalography (paired-pulse TMS-EEG) and pharmacology to directly investigate mechanisms of LICI at the cortical level. We tested the effects of a conditioning stimulus (CS100) applied 100ms prior to a test stimulus (TS) over primary motor cortex on TS-evoked EEG-potentials (TEPs). Healthy subjects were given a single oral dose of baclofen, a GABABR agonist, or diazepam, a positive modulator at GABAARs, in a placebo-controlled, pseudo-randomized double-blinded crossover study. LICI was quantified as the difference between paired-pulse TEPs (corrected for long-lasting EEG responses by the conditioning pulse) minus single-pulse TEPs. LICI at baseline (i.e. pre-drug intake) was characterized by decreased P25, N45, N100 and P180 and increased P70 TEP components. Baclofen resulted in a trend towards the enhancement of LICI of the N45 and N100, and significantly enhanced LICI of the P180. In contrast, diazepam consistently suppressed LICI of late potentials (i.e. N100, P180), without having an effect on LICI of earlier (i.e. P25, N45 and P70) potentials. These findings demonstrate for the first time directly at the system level of the human cortex that GABABR-mediated cortical inhibition contributes to LICI, while GABAAR-mediated inhibition occludes LICI. Paired-pulse TMS-EEG allows investigating cortical GABABR-mediated inhibition more directly and specifically than hitherto possible, and may thus inform on network abnormalities caused by disordered inhibition, e.g. in patients with schizophrenia or epilepsy.

The effect of mindfulness on the inflammatory, psychological and biomechanical domains of adult patients with low back pain: A randomized controlled clinical trial.

OBJECTIVE: This study aims to study the effect of mindfulness-based program on the psychological, biomechanical and inflammatory domains of patients with chronic low back pain. METHODS: A multicentre randomized and controlled clinical trial of parallel groups in patients with chronic low back pain between March 2019 to March 2020. Participants with no experience in mindfulness based intervention, were randomized to receive (36 patients) or not (34 patients) mindfulness-based stress reduction program for chronic back pain (MBSR-CBP). The program was performed in 9 sessions. Patients with chronic low back pain due to symptomatic discopathy (degenerative disc disease or herniated disc) were included. The principal outcome was changes in the blood level of cortisol and cytokines (tumor necrosis factor- α (TNF- α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and interleukin-17 (IL-17)). Secondary outcomes (psychological factors, pain, and quality of life) were measured by validated questionnaires. RESULTS: Of the 96 randomized patients, 70 who completed the study were included in the analysis (mean [range] age: 53 [33-73] years; 66% females). MBSR-CBP stopped the increase in cortisol, and reduced pro-inflammatory cytokine IL-1ß (p = 0.05). It reduced depression (p = 0.046) and stress (p = 0.0438), perceived pain (p < 0.0001), and limitations related to health (p < 0.0001). It also increased the physical function (p = 0.002) and sleep quality (p = 0.05). Furthermore, it significantly increased life satisfaction (0.006), well-being (p = 0.001) and vitality (p < 0.0001). It also increased self-compassion (p < 0.0001) and significantly reduced the overidentification (p<0.0001) and catastrophization (p = 0.002). CONCLUSIONS: MBSR-CBP could be part of a multidisciplinary approach in the management of patients suffering from chronic low back pain.

Principles of recovery from traumatic brain injury: reorganization of functional networks.

Recovery after brain injury is an excellent platform to study the mechanism underlying brain plasticity, the reorganization of networks. Do complex network measures capture the physiological and cognitive alterations that occurred after a traumatic brain injury and its recovery? Patients as well as control subjects underwent resting-state MEG recording following injury and after neurorehabilitation. Next, network measures such as network strength, path length, efficiency, clustering and energetic cost were calculated. We show that these parameters restore, in many cases, to control ones after recovery, specifically in delta and alpha bands, and we design a model that gives some hints about how the functional networks modify their weights in the recovery process. Positive correlations between complex network measures and some of the general index of the WAIS-III test were found: changes in delta-based path-length and those in Performance IQ score, and alpha-based normalized global efficiency and Perceptual Organization Index. These results indicate that: 1) the principle of recovery depends on the spectral band, 2) the structure of the functional networks evolves in parallel to brain recovery with correlations with neuropsychological scales, and 3) energetic cost reveals an optimal principle of recovery.

Reorganization of functional connectivity as a correlate of cognitive recovery in acquired brain injury.

Cognitive processes require a functional interaction between specialized multiple, local and remote brain regions. Although these interactions can be strongly altered by an acquired brain injury, brain plasticity allows network reorganization to be principally responsible for recovery. The present work evaluates the impact of brain injury on functional connectivity patterns. Networks were calculated from resting-state magnetoencephalographic recordings from 15 brain injured patients and 14 healthy controls by means of wavelet coherence in standard frequency bands. We compared the parameters defining the network, such as number and strength of interactions as well as their topology, in controls and patients for two conditions: following a traumatic brain injury and after a rehabilitation treatment. A loss of delta- and theta-based connectivity and conversely an increase in alpha- and beta-band-based connectivity were found. Furthermore, connectivity parameters approached controls in all frequency bands, especially in slow-wave bands. A correlation between network reorganization and cognitive recovery was found: the reduction of delta-band-based connections and the increment of those based on alpha band correlated with Verbal Fluency scores, as well as Perceptual Organization and Working Memory Indexes, respectively. Additionally, changes in connectivity values based on theta and beta bands correlated with the Patient Competency Rating Scale. The current study provides new evidence of the neurophysiological mechanisms underlying neuronal plasticity processes after brain injury, and suggests that these changes are related with observed changes at the behavioural level.

Oscillatory activity in prefrontal and posterior regions during implicit letter-location binding.

Many cognitive abilities involve the integration of information from different modalities, a process referred to as "binding." It remains less clear, however, whether the creation of bound representations occurs in an involuntary manner, and whether the links between the constituent features of an object are symmetrical. We used magnetoencephalography to investigate whether oscillatory brain activity related to binding processes would be observed in conditions in which participants maintain one feature only (involuntary binding); and whether this activity varies as a function of the feature attended to by participants (binding asymmetry). Participants performed two probe recognition tasks that were identical in terms of their perceptual characteristics and only differed with respect to the instructions given (to memorize either consonants or locations). MEG data were reconstructed using a current source distribution estimation in the classical frequency bands. We observed implicit verbal-spatial binding only when participants successfully maintained the identity of consonants, which was associated with a selective increase in oscillatory activity over prefrontal regions in all frequency bands during the first half of the retention period and accompanied by increased activity in posterior brain regions. The increase in oscillatory activity in prefrontal areas was only observed during the verbal task, which suggests that this activity might be signaling neural processes specifically involved in cross-code binding. Current results are in agreement with proposals suggesting that the prefrontal cortex function as a "pointer" which indexes the features that belong together within an object.

Key Bacteria in the Gut Microbiota Network for the Transition between Sedentary and Active Lifestyle.

Physical activity modifies the gut microbiota, exerting health benefits on the host; however, the specific bacteria associated with exercise are not yet known. In this work, we propose a novel method, based on hierarchical topology, to study the differences between the microbiota of active and sedentary lifestyles, and to identify relevant bacterial taxa. Our results show that the microbiota network found in active people has a significantly higher overall efficiency and higher transmissibility rate. We also identified key bacteria in active and sedentary networks that could be involved in the conversion of an active microbial network to a sedentary microbial network and vice versa.

Neuron synchronization in the rat gracilis nucleus facilitates sensory transmission in the somatosensory pathway.

We have studied the role of the temporal correlation of multiple cell discharges in the facilitation of the somatosensory information transmission from the gracilis nucleus to the primary somatosensory (SI) cortex in anesthetized rats. Pairs of gracilis neurons or gracilis-SI cortical neurons were recorded during application of 20-ms tactile stimuli in control conditions and after electrical corticofugal stimulation. Cross-correlation of neural spike trains showed significant changes in synchronization of the neuron firing provoked by the corticofugal stimulation. To quantify the time-frequency alterations in the functional association within neuron pairs we used the wavelet coherence measure. We show that electrical stimulation of the SI cortex induces a short-lasting facilitation of tactile responses of projecting gracilis neurons if their receptive fields (RFs) overlap with the RF of the stimulated cortical area (matching condition). Moreover, synchronization of discharges of gracilis neurons with a common RF is increased by activation of the corticofugal projection. Synchronization is favored by a stimulus induced synchronous oscillatory activity of projecting neurons in the range 3-10 Hz. In the matching condition synchronous discharges in the gracilis increment the number of spikes elicited in the SI cortex. Thus the efficacy of the sensory transmission from the gracilis nucleus to the SI cortex is modulated by the corticofugal projection through two complementary mechanisms: (i) by changing the responsiveness (number of elicited spikes) of individual gracilis neurons; and (ii) by a dynamic consolidation of gracilis neurons with a common RF into microcircuits generating synchronous spikes.

Stimulus-dependent interaction between the visual areas 17 and 18 of the 2 hemispheres of the ferret (Mustela putorius).

To study how the visual areas of the 2 hemispheres interact in processing visual stimuli we have recorded local field potentials in the callosally connected parts of areas 17 and 18 of the ferret during the presentation of 3 kinds of stimuli: 2.5 degrees squares flashed for 50 ms randomly in the visual field (S1), 4 full-field gratings differing in orientation by 45 degrees and identical in the 2 hemifields (S2) and gratings as above but whose orientation and/or direction of motion differed by 90 degrees in the 2 hemifields (S3). The gratings remained stationary for 0.5 s and then moved in 1 of the 2 directions perpendicular to their orientation for 3 s. We compared the responses in baseline conditions with those obtained whereas the contralateral visual areas were inactivated by cooling. Cooling did not affect the responses to S1 but it modified those to S2 and to S3 generally increasing early components of the response while decreasing later components. These findings indicate that interhemispheric processing is restricted to visual stimuli which achieve spatial summation and that it involves complex inhibitory and facilitatory effects, possibly carried out by interhemispheric pathways of different conduction velocity.

Does mindfulness change the mind? A novel psychonectome perspective based on Network Analysis.

If the brain is a complex network of functionally specialized areas, it might be expected that mental representations could also behave in a similar way. We propose the concept of 'psychonectome' to formalize the idea of psychological constructs forming a dynamic network of mutually dependent elements. As a proof-of-concept of the psychonectome, networks analysis (NA) was used to explore structural changes in the network of constructs resulting from a psychological intervention. NA was applied to explore the effects of an 8-week Mindfulness-Based Stress Reduction (MBSR) program in healthy participants (N = 182). Psychological functioning was measured by questionnaires assessing five key domains related to MBSR: mindfulness, compassion, psychological well-being, psychological distress and emotional-cognitive control. A total of 25 variables, covering the five constructs, were considered as nodes in the NA. Participants significantly improved in most of the psychological questionnaires. More interesting from a network perspective, there were also significant changes in the topological relationships among the elements. Expected influence and strength centrality indexes revealed that mindfulness and well-being measures were the most central nodes in the networks. The nodes with highest topological change after the MBSR were attentional control, compassion measures, depression and thought suppression. Also, cognitive appraisal, an adaptive emotion regulation strategy, was associated to rumination before the MBSR program but became related to mindfulness and well-being measures after the program. Community analysis revealed a strong topological association between mindfulness, compassion, and emotional regulation, which supports the key role of compassion in mindfulness training. These results highlight the importance of exploring psychological changes from a network perspective and support the conceptual advantage of considering the interconnectedness of psychological constructs in terms of a 'psychonectome' as it may reveal ways of functioning that cannot be analyzed through conventional analytic methods.

A Critical Mutualism - Competition Interplay Underlies the Loss of Microbial Diversity in Sedentary Lifestyle.

Physical exercise improves the overall health status by preventing the development of several diseases. In recent years, it has been observed that physical exercise impacts gut microbiota by increasing the presence of beneficial bacteria and microbial diversity. In contrast, a sedentary lifestyle increases the incidence of chronic diseases that often have an associated loss of microbial diversity. The gut microbiota is a vast ecosystem in which microorganisms interact with each other in different ways; however, microbial ecosystem interactions are scarcely studied. The goal of this study was to determine whether individuals with a sedentary lifestyle have lower diversity in their gut microbiota and how microbial diversity is associated with changes in bacterial network interactions. For that purpose, diet, body composition, physical activity, and sedentarism behavior were characterized for individuals who did or did not comply with the World Health Organization recommendations for physical activity. The composition of the gut microbiome was determined by 16S rRNA gene sequencing. Reorganization of microbial structure with lifestyle was approached from network analysis, where network complexity and the topology of positive and negative interdependences between bacteria were compared and correlated with microbial diversity. Sedentary lifestyle was significantly associated with a diet low in fiber and rich in sugars and processed meat, as well as with high visceral and total corporal fat composition. The diversity (phylogenic diversity, Chao, observed species, and Shannon's index) and network complexity of the gut microbiota were significantly lower in sedentary compared to active individuals. Whereas mutualism or co-occurrence interactions were similar between groups, competitiveness was significantly higher in the active lifestyle group. The mutualism-competition ratio was moderate and positively associated with diversity in sedentary individuals, but not in active individuals. This finding indicates that there is a critical point in this ratio beyond which the stability of the microbial community is lost, inducing a loss of diversity.

Cortical Excitability and Interhemispheric Connectivity in Early Relapsing-Remitting Multiple Sclerosis Studied With TMS-EEG.

Evoked potentials (EPs) are well established in clinical practice for diagnosis and prognosis in multiple sclerosis (MS). However, their value is limited to the assessment of their respective functional systems. Here, we used transcranial magnetic stimulation (TMS) coupled with electroencephalography (TMS-EEG) to investigate cortical excitability and spatiotemporal dynamics of TMS-evoked neural activity in MS patients. Thirteen patients with early relapsing-remitting MS (RRMS) with a median Expanded Disability Status Scale (EDSS) of 1.0 (range 0-2.5) and 16 age- and gender-matched healthy controls received single-pulse TMS of left and right primary motor cortex (L-M1 and R-M1), respectively. Resting motor threshold for L-M1 and R-M1 was increased in MS patients. Latencies and amplitudes of N45, P70, N100, P180, and N280 TMS-evoked EEG potentials (TEPs) were not different between groups, except a significantly increased amplitude of the N280 TEP in the MS group, both for L-M1 and R-M1 stimulation. Interhemispheric signal propagation (ISP), estimated from the area under the curve of TEPs in the non-stimulated vs. stimulated M1, also did not differ between groups. In summary, findings show that ISP and TEPs were preserved in early-stage RRMS, except for an exaggerated N280 amplitude. Our findings indicate that TMS-EEG is feasible in testing excitability and connectivity in cortical neural networks in MS patients, complementary to conventional EPs. However, relevance and pathophysiological correlates of the enhanced N280 will need further study.

Recovering EEG brain signals: artifact suppression with wavelet enhanced independent component analysis.

Independent component analysis (ICA) has been proven useful for suppression of artifacts in EEG recordings. It involves separation of measured signals into statistically independent components or sources, followed by rejection of those deemed artificial. We show that a "leak" of cerebral activity of interest into components marked as artificial means that one is going to lost that activity. To overcome this problem we propose a novel wavelet enhanced ICA method (wICA) that applies a wavelet thresholding not to the observed raw EEG but to the demixed independent components as an intermediate step. It allows recovering the neural activity present in "artificial" components. Employing semi-simulated and real EEG recordings we quantify the distortions of the cerebral part of EEGs introduced by the ICA and wICA artifact suppressions in the time and frequency domains. In the context of studying cortical circuitry we also evaluate spectral and partial spectral coherences over ICA/wICA-corrected EEGs. Our results suggest that ICA may lead to an underestimation of the neural power spectrum and to an overestimation of the coherence between different cortical sites. wICA artifact suppression preserves both spectral (amplitude) and coherence (phase) characteristics of the underlying neural activity.

Hyperconnectivity is a fundamental response to neurological disruption.

OBJECTIVE: In the cognitive and clinical neurosciences, the past decade has been marked by dramatic growth in a literature examining brain "connectivity" using noninvasive methods. We offer a critical review of the blood oxygen level dependent functional MRI (BOLD fMRI) literature examining neural connectivity changes in neurological disorders with focus on brain injury and dementia. The goal is to demonstrate that there are identifiable shifts in local and large-scale network connectivity that can be predicted by the degree of pathology. We anticipate that the most common network response to neurological insult is hyperconnectivity but that this response depends upon demand and resource availability. METHOD: To examine this hypothesis, we initially reviewed the results from 1,426 studies examining functional brain connectivity in individuals diagnosed with multiple sclerosis, traumatic brain injury, mild cognitive impairment, and Alzheimer's disease. Based upon inclusionary criteria, 126 studies were included for detailed analysis. RESULTS: RESULTS from 126 studies examining local and whole brain connectivity demonstrated increased connectivity in traumatic brain injury and multiple sclerosis. This finding is juxtaposed with findings in mild cognitive impairment and Alzheimer's disease where there is a shift to diminished connectivity as degeneration progresses. CONCLUSION: This summary of the functional imaging literature using fMRI methods reveals that hyperconnectivity is a common response to neurological disruption and that it may be differentially observable across brain regions. We discuss the factors contributing to both hyper- and hypoconnectivity results after neurological disruption and the implications these findings have for network plasticity.

Influence of the APOE ε4 allele and mild cognitive impairment diagnosis in the disruption of the MEG resting state functional connectivity in sources space.

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.

Cognitive reserve is associated with the functional organization of the brain in healthy aging: a MEG study.

The proportion of elderly people in the population has increased rapidly in the last century and consequently "healthy aging" is expected to become a critical area of research in neuroscience. Evidence reveals how healthy aging depends on three main behavioral factors: social lifestyle, cognitive activity, and physical activity. In this study, we focused on the role of cognitive activity, concentrating specifically on educational and occupational attainment factors, which were considered two of the main pillars of cognitive reserve (CR). Twenty-one subjects with similar rates of social lifestyle, physical and cognitive activity were selected from a sample of 55 healthy adults. These subjects were divided into two groups according to their level of CR; one group comprised subjects with high CR (9 members) and the other one contained those with low CR (12 members). To evaluate the cortical brain connectivity network, all participants were recorded by Magnetoencephalography (MEG) while they performed a memory task (modified version of the Sternberg's Task). We then applied two algorithms [Phase Locking Value (PLV) and Phase Lag Index (PLI)] to study the dynamics of functional connectivity. In response to the same task, the subjects with lower CR presented higher functional connectivity than those with higher CR. These results may indicate that participants with low CR needed a greater "effort" than those with high CR to achieve the same level of cognitive performance. Therefore, we conclude that CR contributes to the modulation of the functional connectivity patterns of the aging brain.