Remodeling of brain morphology in temporal lobe epilepsy.

Mesial temporal lobe epilepsy (TLE) is one of the most widespread neurological network disorders. Computational anatomy MRI studies demonstrate a robust pattern of cortical volume loss. Most statistical analyses provide information about localization of significant focal differences in a segregationist way. Multivariate Bayesian modeling provides a framework allowing inferences about inter-regional dependencies. We adopt this approach to answer following questions: Which structures within a pattern of dynamic epilepsy-associated brain anatomy reorganization best predict TLE pathology. Do these structures differ between TLE subtypes? We acquire clinical and MRI data from TLE patients with and without hippocampus sclerosis (n = 128) additional to healthy volunteers (n = 120). MRI data were analyzed in the computational anatomy framework of SPM12 using classical mass-univariate analysis followed by multivariate Bayesian modeling. After obtaining TLE-associated brain anatomy pattern, we estimate predictive power for disease and TLE subtypes using Bayesian model selection and comparison. We show that ipsilateral para-/hippocampal regions contribute most to disease-related differences between TLE and healthy controls independent of TLE laterality and subtype. Prefrontal cortical changes are more discriminative for left-sided TLE, whereas thalamus and temporal pole for right-sided TLE. The presence of hippocampus sclerosis was linked to stronger involvement of thalamus and temporal lobe regions; frontoparietal involvement was predominant in absence of sclerosis. Our topology inferences on brain anatomy demonstrate a differential contribution of structures within limbic and extralimbic circuits linked to main effects of TLE and hippocampal sclerosis. We interpret our results as evidence for TLE-related spatial modulation of anatomical networks

in search of the neurobiological basis of divergent thinking

Human mind can follow two opposite types of reasoning in everyday life as well as in science: convergent thinking, as the ability to get the unique solution to a problem, or divergent thinking, the ability to elaborate different answer to a question. The latter is usually considered as an essential feature of the "creative mind", together with Insight, an unpredictable and unexpected moment of exceptional thinking commonly reported as the "Eureka!" experience. During such processing, an unconscious reorganization process of previously unrelated problem elements is made and when the solution finally emerges to consciousness, the subject is not able to explain how he/she reached it. Because of its unpredictable and unconscious nature, as well as its connection with creativity and scientific discoveries, the definition and evaluation of insight is now one of the biggest challenges for modern cognitive neuroscience. Neurophysiological evidence begins to arise, making the enhancement of creativity thinking using non-invasive neuromodulation techniques a plausible future scenario

Neural correlates of N-back task performance and proposal for corresponding neuromodulation targets in psychiatric and neurodevelopmental disorders

Aim: Working memory (WM) deficit represents the most common cognitive impairment in psychiatric and neurodevelopmental disorders, making the identification of its neural substrates a crucial step towards the conceptualization of restorative interventions. We present a meta-analysis focusing on neural activations associated with the most commonly used task to measure WM, the N-back task, in patients with schizophrenia, depressive disorder, bipolar disorder, and attention-deficit/hyperactivity disorder. Showing qualitative similarities and differences in WM processing between patients and healthy controls, we propose possible targets for cognitive enhancement approaches. Methods: Selected studies, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, were analyzed through the activation likelihood estimate statistical framework, with subsequent generation of disorder-specific N-back activation maps. Results: Despite similar WM deficits shared across all disorders, results highlighted different brain activation patterns for each disorder compared with healthy controls. In general, results showed brain activity in frontal, parietal, subcortical, and cerebellar regions; however, reduced engagement of specific nodes of the fronto-parietal network emerged in patients compared with healthy controls. In particular, neither bipolar nor depressive disorders showed detectable activations in the dorsolateral prefrontal cortices, while their parietal activation patterns were lateralized to the left and right hemispheres, respectively. On the other hand, patients with attention-deficit/hyperactivity disorder showed a lack of activation in the left parietal lobe, whereas patients with schizophrenia showed lower activity over the left prefrontal cortex. Conclusion: These results, together with biophysical modeling, were then used to discuss the design of future disorder-specific cognitive enhancement interventions based on noninvasive brain stimulation

Personalised, image-guided, noninvasive brain stimulation in gliomas: Rationale, challenges and opportunities

Malignant brain tumours are among the most aggressive human cancers, and despite intensive efforts made over the last decades, patients’ survival has scarcely improved. Recently, high-grade gliomas (HGG) have been found to be electrically integrated with healthy brain tissue, a communication that facilitates tumour mitosis and invasion. This link to neuronal activity has provided new insights into HGG pathophysiology and opened prospects for therapeutic interventions based on electrical modulation of neural and synaptic activity in the proximity of tumour cells, which could potentially slow tumour growth. Noninvasive brain stimulation (NiBS), a group of techniques used in research and clinical settings to safely modulate brain activity and plasticity via electromagnetic or electrical stimulation, represents an appealing class of interventions to characterise and target the electrical properties of tumour-neuron interactions. Beyond neuronal activity, NiBS may also modulate function of a range of substrates and dynamics that locally interacts with HGG (e.g., vascular architecture, perfusion and blood-brain barrier permeability). Here we discuss emerging applications of NiBS in patients with brain tumours, covering potential mechanisms of action at both cellular, regional, network and whole-brain levels, also offering a conceptual roadmap for future research to prolong survival or promote wellbeing via personalised NiBS interventions

Tumor BOLD connectivity profile correlates with glioma patients' survival

Background: Presence of residual neurovascular activity within glioma lesions have been recently demonstrated via functional MRI (fMRI) along with active electrical synapses between glioma cells and healthy neurons that influence survival. In this study, we aimed to investigate whether gliomas demonstrate synchronized neurovascular activity with the rest of the brain, by measuring Blood Oxygen Level Dependent (BOLD) signal synchronization, that is, functional connectivity (FC), while also testing whether the strength of such connectivity might predict patients' overall survival (OS). Methods: Resting-state fMRI scans of patients who underwent pre-surgical brain mapping were analyzed (total sample, n = 54; newly diagnosed patients, n = 18; recurrent glioma group, n = 36). A seed-To-voxel analysis was conducted to estimate the FC signal profile of the tumor mass. A regression model was then built to investigate the potential correlation between tumor FC and individual OS. Finally, an unsupervised, cross-validated clustering analysis was performed including tumor FC and clinical OS predictors (e.g., Karnofsky Performance Status-KPS-score, tumor volume, and genetic profile) to verify the performance of tumor FC in predicting OS with respect to validated radiological, demographic, genetic and clinical prognostic factors. Results: In both newly diagnosed and recurrent glioma patients a significant pattern of BOLD synchronization between the solid tumor and distant brain regions was found. Crucially, glioma-brain FC positively correlated with variance in individual survival in both newly diagnosed glioma group (r = 0.90-0.96; P <. 001; R2 = 81-92%) and in the recurrent glioma group (r = 0.72; P <. 001; R2 = 52%), outperforming standard clinical, radiological and genetic predictors. Conclusions: Results suggest glioma's synchronization with distant brain regions should be further explored as a possible diagnostic and prognostic biomarker

Optimizing transcranial magnetic stimulation for spaceflight applications

As space agencies aim to reach and build installations on Mars, the crews will face longer exposure to extreme environments that may compromise their health and performance. Transcranial magnetic stimulation (TMS) is a painless non-invasive brain stimulation technique that could support space exploration in multiple ways. However, changes in brain morphology previously observed after long-term space missions may impact the efficacy of this intervention. We investigated how to optimize TMS for spaceflight-associated brain changes. Magnetic resonance imaging T1-weighted scans were collected from 15 Roscosmos cosmonauts and 14 non-flyer participants before, after 6 months on the International Space Station, and at a 7-month follow-up. Using biophysical modeling, we show that TMS generates different modeled responses in specific brain regions after spaceflight in cosmonauts compared to the control group. Differences are related to spaceflight-induced structural brain changes, such as those impacting cerebrospinal fluid volume and distribution. We suggest solutions to individualize TMS to enhance its efficacy and precision for potential applications in long-duration space missions. © 2023, The Author(s)

Overlapping and dissociable brain activations for fluid intelligence and executive functions

Cognitive enhancement interventions aimed at boosting human fluid intelligence (gf) have targeted executive functions (EFs), such as updating, inhibition, and switching, in the context of transfer-inducing cognitive training. However, even though the link between EFs and gf has been demonstrated at the psychometric level, their neurofunctional overlap has not been quantitatively investigated. Identifying whether and how EFs and gf might share neural activation patterns could provide important insights into the overall hierarchical organization of human higher-order cognition, as well as suggest specific targets for interventions aimed at maximizing cognitive transfer. We present the results of a quantitative meta-analysis of the available fMRI and PET literature on EFs and gf in humans, showing the similarity between gf and (i) the overall global EF network, as well as (ii) specific maps for updating, switching, and inhibition. Results highlight a higher degree of similarity between gf and updating (80% overlap) compared with gf and inhibition (34%), and gf and switching (17%). Moreover, three brain regions activated for both gf and each of the three EFs also were identified, located in the left middle frontal gyrus, left inferior parietal lobule, and anterior cingulate cortex. Finally, resting-state functional connectivity analysis on two independent fMRI datasets showed the preferential behavioural correlation and anatomical overlap between updating and gf. These findings confirm a close link between gf and EFs, with implications for brain stimulation and cognitive training interventions

Local and Distributed fMRI Changes Induced by 40 Hz Gamma tACS of the Bilateral Dorsolateral Prefrontal Cortex: A Pilot Study

Over the past few years, the possibility of modulating fast brain oscillatory activity in the gamma (γ) band through transcranial alternating current stimulation (tACS) has been discussed in the context of both cognitive enhancement and therapeutic scenarios. However, the effects of tACS targeting regions outside the motor cortex, as well as its spatial specificity, are still unclear. Here, we present a concurrent tACS-fMRI block design study to characterize the impact of 40 Hz tACS applied over the left and right dorsolateral prefrontal cortex (DLPFC) in healthy subjects. Results suggest an increase in blood oxygenation level-dependent (BOLD) activity in the targeted bilateral DLPFCs, as well as in surrounding brain areas affected by stimulation according to biophysical modeling, i.e., the premotor cortex and anterior cingulate cortex (ACC). However, off-target effects were also observed, primarily involving the visual cortices, with further effects on the supplementary motor areas (SMA), left subgenual cingulate, and right superior temporal gyrus. The specificity of 40 Hz tACS over bilateral DLPFC and the possibility for network-level effects should be considered in future studies, especially in the context of recently promoted gamma-induction therapeutic protocols for neurodegenerative disorders. © 2022 Lucia Mencarelli et al

The Pathophysiological Underpinnings of Gamma-Band Alterations in Psychiatric Disorders

Investigating the biophysiological substrates of psychiatric illnesses is of great interest to our understanding of disorders' etiology, the identification of reliable biomarkers, and potential new therapeutic avenues. Schizophrenia represents a consolidated model of gamma alterations arising from the aberrant activity of parvalbumin-positive GABAergic interneurons, whose dysfunction is associated with perineuronal net impairment and neuroinflammation. This model of pathogenesis is supported by molecular, cellular, and functional evidence. Proof for alterations of gamma oscillations and their underlying mechanisms has also been reported in bipolar disorder and represents an emerging topic for major depressive disorder. Although evidence from animal models needs to be further elucidated in humans, the pathophysiology of gamma-band alteration represents a common denominator for different neuropsychiatric disorders. The purpose of this narrative review is to outline a framework of converging results in psychiatric conditions characterized by gamma abnormality, from neurochemical dysfunction to alterations in brain rhythms

A magnetic compatible supernumerary robotic finger for functional magnetic resonance imaging (fMRI) acquisitions: Device description and preliminary results

The Supernumerary robotic limbs are a recently introduced class of wearable robots that, differently from traditional prostheses and exoskeletons, aim at adding extra effectors (i.e., arms, legs, or fingers) to the human user, rather than substituting or enhancing the natural ones. However, it is still undefined whether the use of supernumerary robotic limbs could specifically lead to neural modifications in brain dynamics. The illusion of owning the part of body has been already proven in many experimental observations, such as those relying on multisensory integration (e.g., rubber hand illusion), prosthesis and even on virtual reality. In this paper we present a description of a novel magnetic compatible supernumerary robotic finger together with preliminary observations from two functional magnetic resonance imaging (fMRI) experiments, in which brain activity was measured before and after a period of training with the robotic device, and during the use of the novel MRI-compatible version of the supernumerary robotic finger. Results showed that the usage of the MR-compatible robotic finger is safe and does not produce artifacts on MRI images. Moreover, the training with the supernumerary robotic finger recruits a network of motor-related cortical regions (i.e. primary and supplementary motor areas), hence the same motor network of a fully physiological voluntary motor gestures