Fernando Maestú

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.

Reorganization of functional networks in mild cognitive impairment.

Whether the balance between integration and segregation of information in the brain is damaged in Mild Cognitive Impairment (MCI) subjects is still a matter of debate. Here we characterize the functional network architecture of MCI subjects by means of complex networks analysis. Magnetoencephalograms (MEG) time series obtained during a memory task were evaluated by synchronization likelihood (SL), to quantify the statistical dependence between MEG signals and to obtain the functional networks. Graphs from MCI subjects show an enhancement of the strength of connections, together with an increase in the outreach parameter, suggesting that memory processing in MCI subjects is associated with higher energy expenditure and a tendency toward random structure, which breaks the balance between integration and segregation. All features are reproduced by an evolutionary network model that simulates the degenerative process of a healthy functional network to that associated with MCI. Due to the high rate of conversion from MCI to Alzheimer Disease (AD), these results show that the analysis of functional networks could be an appropriate tool for the early detection of both MCI and AD.

Spanish language mapping using MEG: a validation study.

The purpose of the present study was to compare magnetoencephalography (MEG) data with the results of the intracarotid amytal procedure (IAP). Twenty-one native Spanish-speaking patients with intractable epilepsy underwent MEG language mapping. A subset of 8 patients also underwent an IAP. With the exception of 2 patients who showed right hemisphere dominance, all other patients showed left hemisphere dominance for language on the MEG recording. The IAP findings were consistent with MEG results in 7 patients. The eighth patient who, according to the MEG data, had probable right hemisphere dominance for language did not show clear hemispheric specialization for language on the IAP and suffered a transient global aphasia following a right temporal lobotomy. These results suggests that MEG-based language mapping can play an important role in presurgical clinical evaluation.

Subjective memory complaints in the elderly: Prevalence and influence of temporal orientation, depression and quality of life in a population-based study in the city of Madrid

Objectives: It is still a matter of debate whether variables such as education, sex, age, personality and others underlie subjective memory complaints (SMC). Our objectives are to study: the prevalence of memory complaints in the city of Madrid, the distribution of complaints in the population according to socio-demographic variables and the related variables like cognitive performance, quality of life, perceived health status and functional ability. To our knowledge, this is the first study about the prevalence of SMC in Spain. Methods: We adopted a transversal descriptive epidemiological study. The survey sample size is 1637 persons above 64 years. SMC were obtained through questions regarding memory complaints. Results: 524 (32.4%) subjects reported SMC. The prevalence of SMC depends on age, education, sex, mood and cognitive performance. SMC rises from 24% in the 65–69 age groups to 57% in the 90 and above group. The percentage of subjects with SMC was 52.8% among persons diagnosed with depression or anxiety, and 28.7% among subjects without. Performance on cognitive tests such as orientation showed that subjects without orientation failures (81%) have a 22.2% SMC frequency and subjects who fail all the orientation items (4%) have a 93% frequency. A logistic regression analysis showed that those variables indicating a better prediction of group membership (SMC vs. controls) were orientation in time, quality of life and depression–anxiety. Conclusion: Complaints reflect various processes and are the result of various elements; however, our study highlights the importance of factors such as cognitive performance, depression–anxiety and quality of life.

HERMES: Towards an Integrated Toolbox to Characterize Functional and Effective Brain Connectivity

The analysis of the interdependence between time series has become an important field of research in the last years, mainly as a result of advances in the characterization of dynamical systems from the signals they produce, the introduction of concepts such as generalized and phase synchronization and the application of information theory to time series analysis. In neurophysiology, different analytical tools stemming from these concepts have added to the ‘traditional’ set of linear methods, which includes the cross-correlation and the coherency function in the time and frequency domain, respectively, or more elaborated tools such as Granger Causality.This increase in the number of approaches to tackle the existence of functional (FC) or effective connectivity (EC) between two (or among many) neural networks, along with the mathematical complexity of the corresponding time series analysis tools, makes it desirable to arrange them into a unified-easy-to-use software package. The goal is to allow neuroscientists, neurophysiologists and researchers from related fields to easily access and make use of these analysis methods from a single integrated toolbox.Here we present HERMES (http://hermes.ctb.upm.es), a toolbox for the Matlab® environment (The Mathworks, Inc), which is designed to study functional and effective brain connectivity from neurophysiological data such as multivariate EEG and/or MEG records. It includes also visualization tools and statistical methods to address the problem of multiple comparisons. We believe that this toolbox will be very helpful to all the researchers working in the emerging field of brain connectivity analysis.

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.

Effects of cholinergic drugs and cognitive training on dementia: 2-year follow-up.

Several studies have shown that pharmacological and cognitive treatments for Alzheimers’s disease improve cognitive function for short periods, but fewer studies have evaluated the efficacy of those treatments for longer (2-year) periods. An initial sample of 68 subjects with mild Alzheimer’s disease underwent clinical and cognitive evaluation. After evaluation, subjects were assigned to four different groups and participated in a 2-year follow-up study. Group 1 (n = 14) received combined drug and cognitive stimulation, group 2 (n = 20) received only drug treatment, group 3 (n = 14) received only cognitive stimulation, and group 4 (n = 30) received no treatment at all. Results confirmed previous investigation, cognitive and combined stimulation improved patients’ performance throughout the 1st year; however, all groups deteriorated gradually throughout the 2nd year of treatment. According to this evidence, it can be concluded that we cannot stop cognitive deterioration after 2 years of treatment, although deterioration is greater and its progress faster in patients not receiving any treatment at all.

The Effect of Souvenaid on Functional Brain Network Organisation in Patients with Mild Alzheimer’s Disease: A Randomised Controlled Study

Background Synaptic loss is a major hallmark of Alzheimer’s disease (AD). Disturbed organisation of large-scale functional brain networks in AD might reflect synaptic loss and disrupted neuronal communication. The medical food Souvenaid, containing the specific nutrient combination Fortasyn Connect, is designed to enhance synapse formation and function and has been shown to improve memory performance in patients with mild AD in two randomised controlled trials. Objective To explore the effect of Souvenaid compared to control product on brain activity-based networks, as a derivative of underlying synaptic function, in patients with mild AD. Design A 24-week randomised, controlled, double-blind, parallel-group, multi-country study. Participants 179 drug-naïve mild AD patients who participated in the Souvenir II study. Intervention Patients were randomised 1∶1 to receive Souvenaid or an iso-caloric control product once daily for 24 weeks. Outcome In a secondary analysis of the Souvenir II study, electroencephalography (EEG) brain networks were constructed and graph theory was used to quantify complex brain structure. Local brain network connectivity (normalised clustering coefficient gamma) and global network integration (normalised characteristic path length lambda) were compared between study groups, and related to memory performance. Results The network measures in the beta band were significantly different between groups: they decreased in the control group, but remained relatively unchanged in the active group. No consistent relationship was found between these network measures and memory performance. Conclusions The current results suggest that Souvenaid preserves the organisation of brain networks in patients with mild AD within 24 weeks, hypothetically counteracting the progressive network disruption over time in AD. The results strengthen the hypothesis that Souvenaid affects synaptic integrity and function. Secondly, we conclude that advanced EEG analysis, using the mathematical framework of graph theory, is useful and feasible for assessing the effects of interventions. Trial registration Dutch Trial Register NTR1975.

Functional Connectivity in Mild Cognitive Impairment During a Memory Task: Implications for the Disconnection Hypothesis

Mild cognitive impairment (MCI) has been considered an intermediate state between healthy aging and dementia. The early damage in anatomical connectivity and progressive loss of synapses that characterize early Alzheimers disease suggest that MCI could also be a disconnection syndrome. Here, we compare the degree of synchronization of brain signals recorded with magnetoencephalography from patients (22) with MCI with that of healthy controls (19) during a memory task. Synchronization Likelihood, an index based on the theory of nonlinear dynamical systems, was used to measure functional connectivity. During the memory task patients showed higher interhemispheric synchronization than healthy controls between left and right -anterior temporo-frontal regions (in all studied frequency bands) and in posterior regions in the γ band. On the other hand, the connectivity pattern from healthy controls indicated two clusters of higher synchronization, one among left temporal sensors and another one among central channels. Both of them were found in all frequency bands. In the γ band, controls showed higher Synchronization Likelihood values than MCI patients between central-posterior and frontal-posterior channels and a high synchronization in posterior regions. The inter-hemispheric increased synchronization values could reflect a compensatory mechanism for the lack of efficiency of the memory networks in MCI patients. Therefore, these connectivity profiles support only partially the idea of MCI as a disconnection syndrome, as patients showed increased long distance inter-hemispheric connections but a decrease in antero-posterior functional connectivity.

Effects of cholinergic drugs and cognitive training on dementia

A study was performed on patients with Alzheimer’s disease (AD) in order to evaluate the efficacy of a combined treatment (donepezil plus cognitive training) in both cognitive processes and affective states. Eighty-six subjects, 25 men and 61 women, with an average age of 75.58 years, were studied. Almost all the subjects had a basic educational level. Donezepil was administered at a dose of 10 mg daily along with cognitive treatment involving images of everyday life and reminiscent music; the sessions took place on Monday to Friday and lasted three quarters of an hour. The study lasted 12 months. Subjects underwent test-retest with the following tests: Mini-Mental State Examination (MMSE), the cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-cog); the Geriatric Depression Scale (GDS) and the overall deterioration scale (FAST). The results showed that subjects receiving the combined treatment had a better response than those who did not receive any cognitive training. These subjects’ MMSE score decreased by 3.24 on average. The affective symptomatology of those receiving only drug treatment improved whereas the cognitive processes did not.