Neuromodulators are endogenous neurochemicals that regulate biophysical and biochemical processes, which control brain function and behaviour, and are often the targets of neuropharmacological drugs. Neuromodulator effects are generally complex partly owing to the involvement of broad innervation, co-release of neuromodulators, complex intra- and extrasynaptic mechanism, existence of multiple receptor subtypes and high interconnectivity within the brain. In this work, we propose an efficient yet sufficiently realistic computational neural modelling framework to study some of these complex behaviours. Specifically, we propose a novel dynamical neural circuit model that integrates the effective neuromodulator-induced currents based on various experimental data (e.g. electrophysiology, neuropharmacology and voltammetry). The model can incorporate multiple interacting brain regions, including neuromodulator sources, simulate efficiently and easily extendable to large-scale brain models, e.g. for neuroimaging purposes. As an example, we model a network of mutually interacting neural populations in the lateral hypothalamus, dorsal raphe nucleus and locus coeruleus, which are major sources of neuromodulator orexin/hypocretin, serotonin and norepinephrine/noradrenaline, respectively, and which play significant roles in regulating many physiological functions. We demonstrate that such a model can provide predictions of systemic drug effects of the popular antidepressants (e.g. reuptake inhibitors), neuromodulator antagonists or their combinations. Finally, we developed user-friendly graphical user interface software for model simulation and visualization for both fundamental sciences and pharmacological studies.

A classic left frontal-temporal brain network is known to support language processes. However, the level of participation of constituent regions, and the contribution of extra-canonical areas, is not fully understood; this is particularly true in children, and in individuals who have experienced early neurological insult. In the present work, we propose whole-brain connectivity and graph-theoretical analysis of magnetoencephalography (MEG) source estimates to provide robust maps of the pediatric expressive language network. We examined neuromagnetic data from a group of typically-developing young children (n = 15, ages 4–6 years) and adolescents (n = 14, 16–18 years) completing an auditory verb generation task in MEG. All source analyses were carried out using a linearly-constrained minimum-variance (LCMV) beamformer. Conventional differential analyses revealed significant (p < 0.05, corrected) low-beta (13–23 Hz) event related desynchrony (ERD) focused in the left inferior frontal region (Broca’s area) in both groups, consistent with previous studies. Connectivity analyses were carried out in broadband (3–30 Hz) on time-course estimates obtained at the voxel level. Patterns of connectivity were characterized by phase locking value (PLV), and network hubs identified through eigenvector centrality (EVC). Hub analysis revealed the importance of left perisylvian sites, i.e., Broca’s and Wernicke’s areas, across groups. The hemispheric distribution of frontal and temporal lobe EVC values was asymmetrical in most subjects; left dominant EVC was observed in 20% of young children, and 71% of adolescents. Interestingly, the adolescent group demonstrated increased critical sites in the right cerebellum, left inferior frontal gyrus (IFG) and left putamen. Here, we show that whole brain connectivity and network analysis can be used to map critical language sites in typical development; these methods may be useful for defining the margins of eloquent tissue in neurosurgical candidates.

Lower-extremity robotic exoskeletons are used in gait rehabilitation to achieve functional motor recovery. To date, little is known about how gait training and post-training are characterized in brain signals and their causal connectivity. In this work, we used time-domain partial Granger causality (PGC) analysis to elucidate the directed functional connectivity of electroencephalogram (EEG) signals of healthy adults in robot-assisted gait training (RAGT). Our results confirm the presence of EEG rhythms and corticomuscular relationships during standing and walking using spectral and coherence analyses. The PGC analysis revealed enhanced connectivity close to sensorimotor areas ( C and CP ) during standing, whereas additional connectivities involve the centroparietal ( CP ) and frontal ( F ) areas during walking with respect to standing. In addition, significant fronto-centroparietal causal effects were found during both training and post-training. Strong correlations were also found between kinematic errors and fronto-centroparietal connectivity during training and post-training. This study suggests fronto-centroparietal connectivity as a potential neuromarker for motor learning and adaptation in RAGT.

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Magnetic resonance imaging (MRI) and positron emission tomography (PET) are neuroimaging modalities typically used for evaluating brain changes in Alzheimer’s disease (AD). Due to their complementary nature, their combination can provide more accurate AD diagnosis or prognosis. In this work, we apply a multi-modal imaging machine-learning framework to enhance AD classification and prediction of diagnosis of subject-matched gray matter MRI and Pittsburgh compound B (PiB)-PET data related to 58 AD, 108 mild cognitive impairment (MCI) and 120 healthy elderly (HE) subjects from the Australian imaging, biomarkers and lifestyle (AIBL) dataset. Specifically, we combined a Dartel algorithm to enhance anatomical registration with multi-kernel learning (MKL) technique, yielding an average of >95% accuracy for three binary classification problems: AD-vs.-HE, MCI-vs.-HE and AD-vs.-MCI, a considerable improvement from individual modality approach. Consistent with t-contrasts, the MKL weight maps revealed known brain regions associated with AD, i.e., (para)hippocampus, posterior cingulate cortex and bilateral temporal gyrus. Importantly, MKL regression analysis provided excellent predictions of diagnosis of individuals by r2 = 0.86. In addition, we found significant correlations between the MKL classification and delayed memory recall scores with r2 = 0.62 (p < 0.01). Interestingly, outliers in the regression model for diagnosis were mainly converter samples with a higher likelihood of converting to the inclined diagnostic category. Overall, our work demonstrates the successful application of MKL with Dartel on combined neuromarkers from different neuroimaging modalities in the AIBL data. This lends further support in favor of machine learning approach in improving the diagnosis and risk prediction of AD.