Brain Connectivity

In Parkinson’s disease (PD), neurodegeneration of dopaminergic systems leads to motor and non-motor abnormalities. Sex might influence the clinical PD phenotypes and progression. Previous molecular imaging data focused only on the nigro-striato-cortical dopamine system that appeared more preserved in women. There is still a lack of evidence on gender/sex differences in the mesolimbic dopaminergic system. We aimed at assessing PD gender differences in both the dopaminergic pathways, by using a brain metabolic connectivity approach. This is based on the evidence of a significant coupling between the neurotransmission and metabolic impairments.

We included 34 idiopathic PD patients (Female/Male: 16/18) and 34 healthy controls for comparison. The molecular architecture of both the dopaminergic networks was estimated throughout partial correlation analyses using brain metabolism data obtained by fluorine-18-fluorodeoxyglucose positron emission tomography (threshold set at p < 0.01, corrected for Bonferroni multiple comparisons).

Male patients were characterized by a widespread altered connectivity in the nigro-striato-cortical network and a sparing of the mesolimbic pathway. On the contrary, PD females showed a severe altered connectivity in the mesolimbic network and only a partial reconfiguration of the nigro-striato-cortical network.

Our findings add remarkable knowledge on the neurobiology of gender differences in PD, with the identification of specific neural vulnerabilities. The gender differences here revealed might be due to the combination of both biological and sociodemographic life factors. Gender differences in PD should be considered also for treatments and the targeting of modifiable risk factors.

Multivariate methods to fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET) brain data enable to reconstruct brain connectivity patterns within and between neurotransmitter systems, thus providing an in vivo window to the functional architecture of these systems. We focused on the dopaminergic nigro-striato-cortical and mesolimbic networks to investigate gender differences in Parkinson's disease. We found specific neural vulnerabilities of the dopaminergic pathways in males and females by using a metabolic connectivity approach. Our study contributes to the knowledge of the biological basis of gender differences in PD, which may lead to different clinical phenotypes. Understanding how gender may influence pathology is critical for prevention and treatment strategies.

With the recent technical advances in brain imaging modalities such as magnetic resonance imaging, positron emission tomography, and functional magnetic resonance imaging (fMRI), researchers' interests have inclined over the years to study brain functions through the analysis of the variations in the statistical dependence among various brain regions. Through its wide use in studying brain connectivity, the low temporal resolution of the fMRI represented by the limited number of samples per second, in addition to its dependence on brain slow hemodynamic changes, makes it of limited capability in studying the fast underlying neural processes during information exchange between brain regions.

In this article, the high temporal resolution of the electroencephalography (EEG) is utilized to estimate the effective connectivity within the default mode network (DMN). The EEG data are collected from 20 subjects with alcoholism and 25 healthy subjects (controls), and used to obtain the effective connectivity diagram of the DMN using the Partial Directed Coherence algorithm.

The resulting effective connectivity diagram within the DMN shows the unidirectional causal effect of each region on the other. The variations in the causal effects within the DMN between controls and alcoholics show clear correlation with the symptoms that are usually associated with alcoholism, such as cognitive and memory impairments, executive control, and attention deficiency. The correlation between the exchanged causal effects within the DMN and symptoms related to alcoholism is discussed and properly analyzed.

The establishment of the causal differences between control and alcoholic subjects within the DMN regions provides valuable insight into the mechanism by which alcohol modulates our cognitive and executive functions and creates better possibility for effective treatment of alcohol use disorder.

Understanding the physiological mechanism by which alcohol modulates the causal connections between the default mode network (DMN) regions establishes the first step toward effective treatment of the alcohol use disorder. In this study, the variations in effective connectivity within DMN due to alcoholism are addressed using 20 Alcoholics EEG data and compared with 25 normal subjects. Significant differences are found in alcoholics than controls represented by less causal effects of the posterior DMN regions on the anterior regions. The main objective of this research is to draw correlation between the variations in DMN causal connections due to heavy alcohol consumption and the symptoms that are usually affiliated with alcoholism. This will allow for better understanding of alcohol effects on human brain and gives the possibility for better intervention scheme.

Bilingualism is considered a cognitive reserve (CR) factor, due to the delay in the onset of dementia in bilinguals compared with monolinguals. Two neural mechanisms have been suggested to underlie CR: neural reserve and neural compensation. However, it is still unclear how bilingualism contributes to these mechanisms.

In this study, we used cognitive tests, functional connectivity (FC), regional homogeneity, and fractional amplitude of low-frequency fluctuations (fALFF) measures to study resting-state brain patterns in a sample of bilingual and monolingual subjects with mild cognitive impairment.

We found no significant differences between the groups in age, sex, education, or cognitive level, but bilinguals showed higher FC than monolinguals between the posterior part of the superior temporal gyrus and the precuneus, positively correlated with Mini-Mental State Examination scores, and higher fALFF in the thalamus bilaterally.

Our results suggest that bilingualism may act as a CR factor that protects against dementia through neural compensation.

Recent investigations suggest that neural compensation is one of the cognitive reserve mechanisms underlying the protection of bilingualism against dementia. Although brain changes in functional connectivity (FC) have been proposed as evidence of this mechanism, no study has directly used FC to study neural compensation in bilingualism. Our findings show that mild cognitive impairment bilinguals manifest higher resting-state FC than monolinguals between the language network and the precuneus, supporting the involvement of neural compensation in the protection of bilingualism against dementia. Moreover, we found bilingualism effects in the spontaneous activity of the thalamus, a region related to atrophy in dementia.

To determine whether Neanderthal-derived genetic variation relates to functional connectivity patterns in the brains of living modern humans.

Nearly 50,000 years ago, Neanderthals interbred with ancestors of modern humans, imparting a genetic legacy that lives on today. The vestiges of this Neanderthal-derived genetic variation have been previously shown to be enriched in genes coding for neurogenesis and myelination and to alter skull shape and brain structure in living people.

Using two independent cohorts totaling 553 healthy individuals, we employed multivariate distance matrix regression (MDMR) to determine whether any brain areas exhibited whole-brain functional connectivity patterns that significantly related to the degree of Neanderthal introgression. Identified clusters were then used as regions of interest in follow-up seed-based functional connectivity analyses to determine the connectivity patterns driving the relationships.

The MDMR analysis revealed that the percentage of Neanderthal-originating polymorphisms was significantly associated with the functional connectivity patterns of an area of the intraparietal sulcus (IPS) that was nearly identical in both cohorts. Using these IPS clusters as regions of interest in seed-based connectivity analyses, we found, again in both cohorts, that individuals with a higher proportion of Neanderthal-derived genetic variation showed increased IPS functional connectivity with visual processing regions, but decreased IPS connectivity with regions underlying social cognition.

These findings demonstrate that the remnants of Neanderthal admixture continue to influence human brain function today, in ways that are consistent with anthropological conceptualizations of Neanderthal phenotypes, including the possibility that Neanderthals may have depended upon visual processing capabilities at the expense of social cognition, and this may have contributed to the extinction of this species through reduced cultural maintenance and inability to cope with fluctuating resources. This and other studies capitalizing on the emerging science surrounding ancient DNA provide a window through which to view an ancient lineage long past.

Few biological enigmas have captivated the contemporary popular mind as much as our distant evolutionary relatives and the nature of the brain, the organ from which all our experiences and volitions arise. The results reported here indicate that gene flow from Neanderthals to modern humans is not just of evolutionary interest, but also influences the function of the living Homo sapiens brain in ways that are consistent with anthropological conceptualizations of Neanderthal culture. These findings, thus, provide a lens through which to view our distant evolutionary relatives who continue to live on as a flicker in our genetic make-up.

How components of the distributed brain networks that support cognition participate in typical functioning remains a largely unanswered question. An important subgroup of regions in the larger network are connector hubs, which are areas that are highly connected to several other functionally specialized sets of regions, and are likely important for sensorimotor integration. The present study attempts to characterize connector hubs involved in typical expressive language functioning using a data-driven, multimodal, full multilayer magnetoencephalography (MEG) connectivity-based pipeline.

Twelve adolescents, 16–18 years of age (five males), participated in this study. Participants underwent MEG scanning during a verb generation task. MEG and structural connectivity were calculated at the whole-brain level. Amplitude/amplitude coupling (AAC) was used to compute functional connections both within and between discrete frequency bins. AAC values were then multiplied by a binary structural connectivity matrix, and then entered into full multilayer network analysis. Initially, hubs were defined based on multilayer versatility and subsequently reranked by a novel measure called delta centrality on interconnectedness (DCI). DCI is defined as the percent change in interfrequency interconnectedness after removal of a hub.

We resolved regions that are important for between-frequency communication among other areas during expressive language, with several potential theoretical and clinical applications that can be generalized to other cognitive domains.

Our multilayer, data-driven framework captures nonlinear connections that span across scales that are often missed in conventional analyses. The present study suggests that crucial hubs may be conduits for interfrequency communication between action and perception systems that are crucial for typical functioning.

We present methodology to characterize regions supporting cross-frequency communication in the distributed language network. There are 3 key innovations: (1) incorporation of a structural connectivity constraint based on diffusion magnetic resonance imaging (MRI), (2) use of a full multilayer framework that captures both within- and between-frequency connections, and (3) introduction of a new metric, delta centrality on interconnectedness (DCI), that quantifies the importance of a region for cross-frequency coupling.

High variability between individuals (i.e., interindividual variability) in response to transcranial direct current stimulation (tDCS) has become a commonly reported issue in the tDCS literature in recent years. Inherent genetic differences between individuals have been proposed as a contributing factor to observed response variability. This study investigated whether tDCS interindividual variability was genetically mediated.

A large sample size of 61 healthy males received cathodal tDCS (c-tDCS) and sham-tDCS of the primary motor cortex at 1 mA and 10 min via 6 × 4 cm active and 7 × 5 cm return electrodes. Corticospinal excitability (CSE) was assessed via 25 single-pulse transcranial magnetic stimulation motor-evoked potentials (MEPs). Intracortical inhibition was assessed via twenty-five 3 msec interstimulus interval (ISI) paired-pulse MEPs, known as short-interval intracortical inhibition (SICI). Intracortical facilitation (ICF) was assessed via twenty-five 10 msec ISI paired-pulse MEPs. Gene variants encoding for excitatory and inhibitory neuroreceptors were determined via saliva samples. Predetermined thresholds and statistical cluster analyses were used to subgroup individuals.

Two distinct subgroups were identified, “responders” reducing CSE following c-tDCS and “nonresponders” showing no reduction or even increase in CSE. Differences in CSE between responders and nonresponders following c-tDCS were not explained by changes in SICI or ICF.

No significant relationships were reported between gene variants and interindividual variability to c-tDCS, suggesting that the chosen gene variants did not influence the activity of the neuroreceptors involved in eliciting changes in CSE in responders following c-tDCS. In this largest c-tDCS study of its kind, novel insights were reported into the contribution genetic factors may play in observed interindividual variability to c-tDCS.

This study adds insight into the issue of interindividual variability to c-tDCS. It highlights not all individuals respond to c-tDCS similarly when exposed to the same stimulus parameters. This disparity in response to c-tDCS between individuals does not appear to be genetically mediated. For c-tDCS to progress to large-scale clinical application, reliability, predictability and reproducibility are essential. Systematically investigating factors contributing to interindividual variability take steps towards this progress the c-tDCS field towards the potential development of screening tools to determine clinical suitability to c-tDCS to ensure its application in those who may benefit the most.