Brain complexity in stroke recovery after bihemispheric transcranial direct current stimulation in mice.

Stroke is one of the leading causes of disability worldwide. There are many different rehabilitation approaches aimed at improving clinical outcomes for stroke survivors. One of the latest therapeutic techniques is the non-invasive brain stimulation. Among non-invasive brain stimulation, transcranial direct current stimulation has shown promising results in enhancing motor and cognitive recovery both in animal models of stroke and stroke survivors. In this framework, one of the most innovative methods is the bihemispheric transcranial direct current stimulation that simultaneously increases excitability in one hemisphere and decreases excitability in the contralateral one. As bihemispheric transcranial direct current stimulation can create a more balanced modulation of brain activity, this approach may be particularly useful in counteracting imbalanced brain activity, such as in stroke. Given these premises, the aim of the current study has been to explore the recovery after stroke in mice that underwent a bihemispheric transcranial direct current stimulation treatment, by recording their electric brain activity with local field potential and by measuring behavioural outcomes of Grip Strength test. An innovative parameter that explores the complexity of signals, namely the Entropy, recently adopted to describe brain activity in physiopathological states, was evaluated to analyse local field potential data. Results showed that stroke mice had higher values of Entropy compared to healthy mice, indicating an increase in brain complexity and signal disorder due to the stroke. Additionally, the bihemispheric transcranial direct current stimulation reduced Entropy in both healthy and stroke mice compared to sham stimulated mice, with a greater effect in stroke mice. Moreover, correlation analysis showed a negative correlation between Entropy and Grip Strength values, indicating that higher Entropy values resulted in lower Grip Strength engagement. Concluding, the current evidence suggests that the Entropy index of brain complexity characterizes stroke pathology and recovery. Together with this, bihemispheric transcranial direct current stimulation can modulate brain rhythms in animal models of stroke, providing potentially new avenues for rehabilitation in humans.

Cognitive resilience/reserve: Myth or reality? A review of definitions and measurement methods.

INTRODUCTION: This review examines the concept of cognitive reserve (CR) in relation to brain aging, particularly in the context of dementia and its early stages. CR refers to an individual's ability to maintain or regain cognitive function despite brain aging, damage, or disease. Various factors, including education, occupation complexity, leisure activities, and genetics are believed to influence CR. METHODS: We revised the literature in the context of CR. A total of 842 articles were identified, then we rigorously assessed the relevance of articles based on titles and abstracts, employing a systematic approach to eliminate studies that did not align with our research objectives. RESULTS: We evaluate-also in a critical way-the methods commonly used to define and measure CR, including sociobehavioral proxies, neuroimaging, and electrophysiological and genetic measures. The challenges and limitations of these measures are discussed, emphasizing the need for more targeted research to improve the understanding, definition, and measurement of CR. CONCLUSIONS: The review underscores the significance of comprehending CR in the context of both normal and pathological brain aging and emphasizes the importance of further research to identify and enhance this protective factor for cognitive preservation in both healthy and neurologically impaired older individuals. HIGHLIGHTS: This review examines the concept of cognitive reserve in brain aging, in the context of dementia and its early stages. We have evaluated the methods commonly used to define and measure cognitive reserve. Sociobehavioral proxies, neuroimaging, and electrophysiological and genetic measures are discussed. The review emphasizes the importance of further research to identify and enhance this protective factor for cognitive preservation.

Complexity analysis from EEG data in congestive heart failure: A study via approximate entropy.

AIM: Congestive heart failure (CHF) is a very complex clinical syndrome that may lead to ischemic cerebral hypoxia condition. The aim of the present study is to analyze the effects of CHF on brain activity through electroencephalographic (EEG) complexity measures, like approximate entropy (ApEn). METHODS: Twenty patients with CHF and 18 healthy elderly people were recruited. ApEn values were evaluated in the total spectrum (0.2-47 Hz) and main EEG frequency bands: delta (2-4 Hz), theta (4-8 Hz), alpha 1 (8-11 Hz), alpha 2 (11-13 Hz), beta 1 (13-20 Hz), beta 2 (20-30 Hz), and gamma (30-45 Hz) to identify differences between CHF group and control. Moreover, a correlation analysis was performed between ApEn parameters and clinical data (i.e., B-type natriuretic peptides (BNP), New York Heart Association (NYHA), and systolic blood pressure (SBP)) within the CHF group. RESULTS: Statistical topographic maps showed statistically significant differences between the two groups in the total spectrum and theta frequency band. Within the CHF group, significant negative correlations were found between total ApEn and BNP in O2 channel and between theta ApEn and NYHA scores in Fp1, Fp2, and Fz channels; instead, a significant positive correlation was found between theta ApEn and SBP in C3 channel and a nearly significant positive correlation was obtained between theta ApEn and SBP in F4 channel. CONCLUSION: EEG abnormalities in CHF are very similar to those observed in cognitive-impaired patients, suggesting analogies between the effects of neurodegeneration and brain chronic hypovolaemia due to heart disorder and underlying high brain sensitivity to CHF.

The Effects of Directional and Non-Directional Stimuli during a Visuomotor Task and Their Correlation with Reaction Time: An ERP Study.

Different visual stimuli can capture and shift attention into different directions. Few studies have explored differences in brain response due to directional (DS) and non-directional visual stimuli (nDS). To explore the latter, event-related potentials (ERP) and contingent negative variation (CNV) during a visuomotor task were evaluated in 19 adults. To examine the relation between task performance and ERPs, the participants were divided into faster (F) and slower (S) groups based on their reaction times (RTs). Moreover, to reveal ERP modulation within the same subject, each recording from the single participants was subdivided into F and S trials based on the specific RT. ERP latencies were analysed between conditions ((DS, nDS); (F, S subjects); (F, S trials)). Correlation was analysed between CNV and RTs. Our results reveal that the ERPs' late components are modulated differently by DS and nDS conditions in terms of amplitude and location. Differences in ERP amplitude, location and latency, were also found according to subjects' performance, i.e., between F and S subjects and trials. In addition, results show that the CNV slope is modulated by the directionality of the stimulus and contributes to motor performance. A better understanding of brain dynamics through ERPs could be useful to explain brain states in healthy subjects and to support diagnoses and personalized rehabilitation in patients with neurological diseases.

The combination of hyperventilation test and graph theory parameters to characterize EEG changes in mild cognitive impairment (MCI) condition.

Hyperventilation (HV) is a voluntary activity that causes changes in the neuronal firing characteristics noticeable in the electroencephalogram (EEG) signals. HV-related changes have been scribed to modulation of pO2/pCO2 blood contents. Therefore, an HV test is routinely used for highlighting brain abnormalities including those depending to neurobiological mechanisms at the basis of neurodegenerative disorders. The main aim of the present paper is to study the effectiveness of HV test in modifying the functional connectivity from the EEG signals that can be typical of a prodromal state of Alzheimer's disease (AD), the Mild Cognitive Impairment prodromal to Alzheimer condition. MCI subjects and a group of age-matched healthy elderly (Ctrl) were enrolled and subjected to EEG recording during HV, eyes-closed (EC), and eyes-open (EO) conditions. Since the cognitive decline in MCI seems to be a progressive disconnection syndrome, the approach we used in the present study is the graph theory, which allows to describe brain networks with a series of different parameters. Small world (SW), modularity (M), and global efficiency (GE) indexes were computed among the EC, EO, and HV conditions comparing the MCI group to the Ctrl one. All the three graph parameters, computed in the typical EEG frequency bands, showed significant changes among the three conditions, and more interestingly, a significant difference in the GE values between the MCI group and the Ctrl one was obtained, suggesting that the combination of HV test and graph theory parameters should be a powerful tool for the detection of possible cerebral dysfunction and alteration.

Approximate entropy analysis across electroencephalographic rhythmic frequency bands during physiological aging of human brain.

Aging is the inevitable biological process that results in a progressive structural and functional decline associated with alterations in the resting/task-related brain activity, morphology, plasticity, and functionality. In the present study, we analyzed the effects of physiological aging on the human brain through entropy measures of electroencephalographic (EEG) signals. One hundred sixty-one participants were recruited and divided according to their age into young (n = 72) and elderly (n = 89) groups. Approximate entropy (ApEn) values were calculated in each participant for each EEG recording channel and both for the total EEG spectrum and for each of the main EEG frequency rhythms: delta (2-4 Hz), theta (4-8 Hz), alpha 1 (8-11 Hz), alpha 2 (11-13 Hz), beta 1 (13-20 Hz), beta 2 (20-30 Hz), and gamma (30-45 Hz), to identify eventual statistical differences between young and elderly. To demonstrate that the ApEn represents the age-related brain changes, the computed ApEn values were used as features in an age-related classification of subjects (young vs elderly), through linear, quadratic, and cubic support vector machine (SVM). Topographic maps of the statistical results showed statistically significant difference between the ApEn values of the two groups found in the total spectrum and in delta, theta, beta 2, and gamma. The classifiers (linear, quadratic, and cubic SVMs) revealed high levels of accuracy (respectively 93.20 ± 0.37, 93.16 ± 0.30, 90.62 ± 0.62) and area under the curve (respectively 0.95, 0.94, 0.93). ApEn seems to be a powerful, very sensitive-specific measure for the study of cognitive decline and global cortical alteration/degeneration in the elderly EEG activity.

Prognostic Role of Hemispherical Functional Connectivity in Stroke: A Study via Graph Theory Versus Coherence of Electroencephalography Rhythms.

BACKGROUND: The objective of the present study is to explore whether acute stroke may result in changes in brain network architecture by electroencephalography functional coupling analysis and graph theory. METHODS: Ninety acute stroke patients and 110 healthy subjects were enrolled in different clinical centers in Rome, Italy, starting from 2013, and for each one electroencephalographies were recorded within <15 days from stroke onset. All patients were clinically evaluated through National Institutes of Health Stroke Scale, Barthel Index, and Action Research Arm Test in the acute stage and during the follow-up. Functional connectivity was assessed using Total Coherence and Small World (SW) by comparing the affected and the unaffected hemisphere between groups (Stroke versus Healthy). Correlations between connectivity and poststroke recovery scores have been carried out. RESULTS: In stroke patients, network hemispheric asymmetry, in terms of Total Coherence, was mainly detected in the affected hemisphere with lower values in Delta, Theta, Alpha1, and Alpha2 (P=0.000001), whereas the unaffected hemisphere showed lower Total Coherence only in Delta and Theta (P=0.000001). SW revealed a significant difference only in the affected hemisphere in all electroencephalography bands (lower SW in Delta (P=0.000003), Theta (P=0.000003), Alpha1 (P=0.000203), and Alpha2 (P=0.028) and higher SW in Beta2 (P=0.000002) and Gamma (P=0.000002)). We also found significant correlations between SW and improvement in National Institutes of Health Stroke Scale (Theta SW: r=-0.2808), Barthel Index (Delta SW: r=0.3692; Theta SW: r=0.3844, Beta2 SW: r=-0.3589; Gamma SW: r=-04948), and Action Research Arm Test (Beta2 SW: r=-0.4274; Gamma SW: r=-0.4370). CONCLUSIONS: These findings demonstrated changes in global functional connectivity and in the balance of network segregation and integration induced by acute stroke. The findings on the correlations between clinical outcome(s) and poststroke network architecture indicate the possibility to identify a predictive index of recovery useful to address and personalize the rehabilitation program.

Time-frequency analysis of brain activity in response to directional and non-directional visual stimuli: an event related spectral perturbations (ERSP) study.

Objective.A large part of the cerebral cortex is dedicated to the processing of visual stimuli and there is still much to understand about such processing modalities and hierarchies. The main aim of the present study is to investigate the differences between directional visual stimuli (DS) and non-directional visual stimuli (n-DS) processing by time-frequency analysis of brain electroencephalographic activity during a visuo-motor task. Electroencephalography (EEG) data were divided into four regions of interest (ROIs) (frontal, central, parietal, occipital).Approach.The analysis of the visual stimuli processing was based on the combination of electroencephalographic recordings and time-frequency analysis. Event related spectral perturbations (ERSPs) were computed with spectrum analysis that allow to obtain the average time course of relative changes induced by the stimulus presentation in spontaneous EEG amplitude spectrum.Main results.Visual stimuli processing enhanced the same pattern of spectral modulation in all investigated ROIs with differences in amplitudes and timing. Additionally, statistically significant differences in occipital ROI between the DS and n-DS visual stimuli processing in theta, alpha and beta bands were found.Significance.These evidences suggest that ERSPs could be a useful tool to investigate the encoding of visual information in different brain regions. Because of their simplicity and their capability in the representation of brain activity, the ERSPs might be used as biomarkers of functional recovery for example in the rehabilitation of visual dysfunction and motor impairment following a stroke, as well as diagnostic tool of anomalies in brain functions in neurological diseases tailored to personalized treatments in clinical environment.

Analysis of complexity in the EEG activity of Parkinson's disease patients by means of approximate entropy.

The objective of the present study is to explore the brain resting state differences between Parkinson's disease (PD) patients and age- and gender-matched healthy controls (elderly) in terms of complexity of electroencephalographic (EEG) signals. One non-linear approach to determine the complexity of EEG is the entropy. In this pilot study, 28 resting state EEGs were analyzed from 13 PD patients and 15 elderly subjects, applying approximate entropy (ApEn) analysis to EEGs in ten regions of interest (ROIs), five for each brain hemisphere (frontal, central, parietal, occipital, temporal). Results showed that PD patients presented statistically higher ApEn values than elderly confirming the hypothesis that PD is characterized by a remarkable modification of brain complexity and globally modifies the underlying organization of the brain. The higher-than-normal entropy of PD patients may describe a condition of low order and consequently low information flow due to an alteration of cortical functioning and processing of information. Understanding the dynamics of brain applying ApEn could be a useful tool to help in diagnosis, follow the progression of Parkinson's disease, and set up personalized rehabilitation programs.

Brain Connectivity and Graph Theory Analysis in Alzheimer's and Parkinson's Disease: The Contribution of Electrophysiological Techniques.

In recent years, applications of the network science to electrophysiological data have increased as electrophysiological techniques are not only relatively low cost, largely available on the territory and non-invasive, but also potential tools for large population screening. One of the emergent methods for the study of functional connectivity in electrophysiological recordings is graph theory: it allows to describe the brain through a mathematic model, the graph, and provides a simple representation of a complex system. As Alzheimer's and Parkinson's disease are associated with synaptic disruptions and changes in the strength of functional connectivity, they can be well described by functional connectivity analysis computed via graph theory. The aim of the present review is to provide an overview of the most recent applications of the graph theory to electrophysiological data in the two by far most frequent neurodegenerative disorders, Alzheimer's and Parkinson's diseases.

Neuronavigated Magnetic Stimulation combined with cognitive training for Alzheimer's patients: an EEG graph study.

Alzheimer's disease (AD) is the most common neurodegenerative disorder in elderly subjects. Recent studies verified the effects of cognitive training combined with repetitive transcranial magnetic stimulation (rTMS-COG) in AD patients. Here, we analyzed neuropsychological and neurophysiological data, derived from electroencephalography (EEG), to evaluate the effects of a 6-week protocol of rTMS-COG in 72 AD. We designed a randomized, double-blind, sham-controlled trial to evaluate efficacy of rTMS on 6 brain regions obtained by an individual MRI combined with COG related to brain areas to stimulate (i.e., syntax and grammar tasks, comprehension of lexical meaning and categorization tasks, action naming, object naming, spatial memory, spatial attention). Patients underwent neuropsychological and EEG examination before (T0), after treatment (T1), and after 40 weeks (T2), to evaluate the effects of rehabilitation therapy. "Small World" (SW) graph approach was introduced allowing us to model the architecture of brain connectivity in order to correlate it with cognitive improvements. We found that following 6 weeks of intensive daily treatment the immediate results showed an improvement in cognitive scales among AD patients. SW present no differences before and after the treatment, whereas a crucial SW modulation emerges at 40-week follow-up, emphasizing the importance of rTMS-COG rehabilitation treatment for AD. Additional results demonstrated that the delta and alpha1 SW seem to be diagnostic biomarkers of AD, whereas alpha2 SW might represent a prognostic biomarker of cognitive recovery. Derived EEG parameters can be awarded the role of diagnostic and predictive biomarkers of AD progression, and rTMS-COG can be regarded as a potentially useful treatment for AD.

Graph Theory on Brain Cortical Sources in Parkinson's Disease: The Analysis of 'Small World' Organization from EEG.

Parkinson's disease (PD) is the second most common neurodegenerative disease in the elderly population. Similarly to other neurodegenerative diseases, the early diagnosis of PD is quite difficult. The current pilot study aimed to explore the differences in brain connectivity between PD and NOrmal eLDerly (Nold) subjects to evaluate whether connectivity analysis may speed up and support early diagnosis. A total of 26 resting state EEGs were analyzed from 13 PD patients and 13 age-matched Nold subjects, applying to cortical reconstructions the graph theory analyses, a mathematical representation of brain architecture. Results showed that PD patients presented a more ordered structure at slow-frequency EEG rhythms (lower value of SW) than Nold subjects, particularly in the theta band, whereas in the high-frequency alpha, PD patients presented more random organization (higher SW) than Nold subjects. The current results suggest that PD could globally modulate the cortical connectivity of the brain, modifying the functional network organization and resulting in motor and non-motor signs. Future studies could validate whether such an approach, based on a low-cost and non-invasive technique, could be useful for early diagnosis, for the follow-up of PD progression, as well as for evaluating pharmacological and neurorehabilitation treatments.