Preconditioning Prefrontal Connectivity Using Transcranial Direct Current Stimulation and Transcranial Magnetic Stimulation

Transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS) have been shown to modulate functional connectivity. Their specific effects seem to be dependent on the pre-existing neuronal state. We aimed to precondition frontal networks using tDCS and subsequently stimulate the left dorsolateral prefrontal cortex (lDLPFC) using TMS. Thirty healthy participants underwent either excitatory, inhibitory or sham tDCS for 10 min, as well as an excitatory intermittent theta burst (iTBS) protocol (600 pulses in 190 s, 20 x 2 s trains), applied over the lDLPFC at 90% of the individual resting motor threshold. Functional connectivity was measured in three task-free, 10-min-long baseline resting state fMRI sessions, immediately before and after tDCS, as well as after iTBS. Connectivity analyses between stimulation site and all other brain voxels, contrasting the interaction effect between the experimental tDCS groups (excitatory vs inhibitory) and the repeated measure (post tDCS vs. post TMS), revealed significantly affected voxels bilaterally in the anterior cingulate and paracingulate gyri, the caudate nuclei, the insula and operculum cortices, as well as the Heschl’s gyrus. ROI-to-ROI analyses additionally showed temporo-parietal-striatal and temporo-parietal-fronto-cingulate differences between the anodal and cathodal group post tDCS, as well as striatal-temporo-parietal anodal-cathodal differences and frontostriatal cathodal-sham group differences post TMS. Excitatory iTBS to a tDCS-inhibited lDLPFC yielded stronger functional connectivity to various areas, as compared to excitatory iTBS to a tDCS-enhanced prefrontal cortex. Results demonstrate complex, whole-brain stimulation effects, most-likely facilitated by cortical homeostatic control mechanisms, as well as the feasibility of using tDCS to modulate TMS effects.

Bilingual experiences induce dynamic structural changes to basal ganglia and the thalamus

Bilingualism has been linked to structural adaptations of subcortical brain regions that are important nodes in controlling of multiple languages. However, research on the location and extent of these adaptations has yielded variable patterns. Existing literature on bilingualism-induced brain adaptations has so far largely overseen evidence from other domains that experience-based structural neuroplasticity often triggers non-linear adaptations which follow expansion-renormalisation trajectories. Here we use generalised additive mixed models (GAMMs) to investigate the non-linear effects of quantified bilingual experiences on the basal ganglia and thalamus in a sample of bilinguals with wide range of bilingual experiences. Our results revealed that volumes of bilateral caudate nuclei and accumbens were positively related to bilingual experiences in a non-linear pattern, with increases followed by decreases, in the most experienced bilinguals, suggesting a return to baseline volume at higher levels of bilingual experience. Moreover, volumes of putamen and thalamus were positively linearly predicted by bilingual experiences. The results offer the first direct evidence that bilingualism, similarly to other cognitively demanding skills, leads to dynamic subcortical structural adaptations which can be nonlinear, in line with expansion-renormalisation models of experience-dependent neuroplasticity.

The Interaction Between Caudate Nucleus and Regions Within the Theory of Mind Network as a Neural Basis for Social Intelligence

The organization of socio-cognitive processes is a multifaceted problem for which many sophisticated concepts have been proposed. One of these concepts is social intelligence (SI), i.e., the set of abilities that allow successful interaction with other people. The theory of mind (ToM) human brain network is a good candidate for the neural substrate underlying SI since it is involved in inferring the mental states of others and ourselves and predicting or explaining others’ actions. However, the relationship of ToM to SI remains poorly explored. Our recent research revealed an association between the gray matter volume of the caudate nucleus and the degree of SI as measured by the Guilford-Sullivan test. It led us to question whether this structural peculiarity is reflected in changes to the integration of the caudate with other areas of the brain associated with socio-cognitive processes, including the ToM system. We conducted seed-based functional connectivity (FC) analysis of resting-state fMRI data for 42 subjects with the caudate as a region of interest. We found that the scores of the Guilford-Sullivan test were positively correlated with the FC between seeds in the right caudate head and two clusters located within the right superior temporal gyrus and bilateral precuneus. Both regions are known to be nodes of the ToM network. Thus, the current study demonstrates that the SI level is associated with the degree of functional integration between the ToM network and the caudate nuclei.

Structural MRI Signatures in Genetic Presentations of the Frontotemporal Dementia-Motor Neuron Disease Spectrum

Objective.To assess cortical, subcortical and cerebellar grey matter (GM) atrophy using magnetic resonance imaging (MRI) in patients with disorders of the frontotemporal lobar degeneration (FTLD) spectrum with known genetic mutations.Methods.Sixty-six patients carrying FTLD-related mutations were enrolled, including 44 with pure motor neuron disease (MND) and 22 with frontotemporal dementia (FTD). Sixty-one patients with sporadic FTLD (sFTLD) matched for age, sex and disease severity with genetic FTLD (gFTLD) were also included, as well as 52 healthy controls. A whole-brain voxel-based morphometry (VBM) analysis was performed. GM volumes of subcortical and cerebellar structures were obtained.Results.Compared with controls, GM atrophy on VBM was greater and more diffuse in genetic FTD, followed by sporadic FTD and genetic MND cases, whereas sporadic MND (sMND) patients showed focal motor cortical atrophy. Patients carrying C9orf72 and GRN mutations showed the most widespread cortical volume loss, in contrast with GM sparing in SOD1 and TARDBP. Globally, gFTLD patients showed greater atrophy of parietal cortices and thalami compared with sFTLD. In volumetric analysis, gFTLD patients showed volume loss compared with sFTLD in the caudate nuclei and thalami, in particular comparing C9-MND with sMND cases. In the cerebellum, gFTLD patients showed greater atrophy of the right lobule VIIb than sFTLD. Thalamic volumes of gFTLD patients with a C9orf72 mutation showed an inverse correlation with Frontal Behavioral Inventory scores.Conclusions.Measures of deep GM and cerebellar structural involvement may be useful markers of gFTLD, particularly C9orf72-related disorders, regardless the clinical presentation within the FTLD spectrum.

Pathologic characterization of canine multiple system degeneration in the Ibizan hound

Canine multiple system degeneration (CMSD) is a progressive hereditary neurodegenerative disorder commonly characterized by neuronal degeneration and loss in the cerebellum, olivary nuclei, substantia nigra, and caudate nuclei. In this article, we describe 3 cases of CMSD in Ibizan hounds. All patients exhibited marked cerebellar ataxia and had cerebellar atrophy on magnetic resonance imaging. At necropsy, all cases showed varying degrees of cerebellar atrophy, and 2 cases had gross cavitation of the caudate nuclei. Histologic findings included severe degeneration and loss of all layers of the cerebellum and neuronal loss and degeneration within the olivary nuclei, substantia nigra, and caudate nuclei. Pedigree analysis indicated an autosomal recessive mode of inheritance, but the causative gene in this breed is yet to be identified. CMSD resembles human multiple system atrophy and warrants further investigation.

Narcissistic personality traits and prefrontal brain structure

Narcissistic traits have been linked to structural and functional brain networks, including the insular cortex, however, with inconsistent findings. In this study, we tested the hypothesis that subclinical narcissism is associated with variations in regional brain volumes in insular and prefrontal areas. We studied 103 clinically healthy subjects, who were assessed for narcissistic traits using the Narcissistic Personality Inventory (NPI, 40-item version) and received high-resolution structural magnetic resonance imaging. Voxel-based morphometry was used to analyse MRI scans and multiple regression models were used for statistical analysis, with threshold-free cluster enhancement (TFCE). We found significant (p < 0.05, family-wise error FWE corrected) positive correlations of NPI scores with grey matter in multiple prefrontal cortical areas (including the medial and ventromedial, anterior/rostral dorsolateral prefrontal and orbitofrontal cortices, subgenual and mid-anterior cingulate cortices, insula, and bilateral caudate nuclei). We did not observe reliable links to particular facets of NPI-narcissism. Our findings provide novel evidence for an association of narcissistic traits with variations in prefrontal and insular brain structure, which also overlap with previous functional studies of narcissism-related phenotypes including self-enhancement and social dominance. However, further studies are needed to clarify differential associations to entitlement vs. vulnerable facets of narcissism.

Mapping the subcortical connectivity of the human default mode network

The default mode network (DMN) mediates self-awareness and introspection, core components of human consciousness. Therapies to restore consciousness in patients with severe brain injuries have historically targeted subcortical sites in the brainstem, thalamus, hypothalamus, basal forebrain, and basal ganglia, with the goal of reactivating cortical DMN nodes. However, the subcortical connectivity of the DMN has not been fully mapped and optimal subcortical targets for therapeutic neuromodulation of consciousness have not been identified. In this work, we created a comprehensive map of DMN subcortical connectivity by combining high-resolution functional and structural datasets with advanced signal processing methods. We analyzed 7 Tesla resting-state functional MRI (rs-fMRI) data from 168 healthy volunteers acquired in the Human Connectome Project. The rs-fMRI blood-oxygen-level-dependent (BOLD) data were temporally synchronized across subjects using the BrainSync algorithm. Cortical and subcortical DMN nodes were jointly analyzed and identified at the group level by applying a novel Nadam-Accelerated SCAlable and Robust (NASCAR) tensor decomposition method to the synchronized dataset. The subcortical connectivity map was then overlaid on a 7 Tesla 100 micron ex vivo MRI dataset for neuroanatomic analysis using automated segmentation of nuclei within the brainstem, thalamus, hypothalamus, basal forebrain, and basal ganglia. We further compared the NASCAR subcortical connectivity map with its counterpart generated from canonical seed-based correlation analyses. The NASCAR method revealed that BOLD signal in the central lateral nucleus of the thalamus and ventral tegmental area of the midbrain is strongly correlated with that of the DMN. In an exploratory analysis, additional subcortical sites in the median and dorsal raphe, lateral hypothalamus, and caudate nuclei were correlated with the cortical DMN. We also found that the putamen and globus pallidus are negatively correlated (i.e., anti-correlated) with the DMN, providing rs-fMRI evidence for the mesocircuit hypothesis of human consciousness, whereby a striatopallidal feedback system modulates anterior forebrain function via disinhibition of the central thalamus. Seed-based analyses yielded similar subcortical DMN connectivity, but the NASCAR result showed stronger contrast and better spatial alignment with dopamine immunostaining data. The DMN subcortical connectivity map identified here advances understanding of the subcortical regions that contribute to human consciousness and can be used to inform the selection of therapeutic targets in clinical trials for patients with disorders of consciousness.

Total and regional ASPECT score for non-contrast CT, CT angiography, and CT perfusion: inter-rater agreement and its association with the final infarction in acute ischemic stroke patients

Background Alberta Stroke Program Early Computed Tomography Score (ASPECTS) is a grading system to assess the extent and distribution of early ischemic changes. Purpose To assess inter-rater agreement for total and regional ASPECTS on non-contrast computed tomography (NCCT) images, CT angiography source images (CTA-SI), and CT-perfusion cerebral blood volume (CTP-CBV) maps, and their association with final infarction in patients with acute ischemic stroke (AIS). Material and Methods A total of 96 consecutive patients with AIS who underwent pre-treatment NCCT and CTP were retrospectively enrolled. CTA-SI was reconstructed using the raw data of CTP. Total and regional ASPECTS were assessed on baseline NCCT, CTA-SI, and CTP-CBV, and on follow-up NCCT or diffusion-weighted imaging. Follow-up ASPECTS served as the reference standard for final infarction. Results CTP-CBV demonstrated higher concordance for total ASPECTS (interclass correlation coefficient, 0.895 vs. 0.771 vs. 0.777) and regional ASPECTS in internal capsule, lentiform, caudate nuclei, M5 and M6, compared with NCCT and CTA-SI. CTP-CBV showed a trend of stronger correlation with final ASPECTS than NCCT and CTA-SI (0.717 vs. 0.711 vs. 0.565; P > 0.05). ASPECTS in the internal capsule (ρ, 0.756 vs. 0.556; P = 0.016) and caudate nucleus (ρ, 0.717 vs. 0.476; P = 0.010) on CTP-CBV were more strongly correlated with follow-up ASPECTS than NCCT. CTP-CBV showed higher accuracy for predicting final infarction in the internal capsule (92.5% vs. 90.3% and 87.1%; P > 1.000, P = 0.125, respectively) and caudate nucleus (87.1% vs. 79.6% and 77.4%; P = 0.453, P = 0.039, respectively) than CTA-SI and NCCT. Conclusion CTP-CBV ASPECTS might be more reliable for delineating early ischemic changes and predicting final infarction.

Posterior Cortical Cognitive Deficits Are Associated With Structural Brain Alterations in Mild Cognitive Impairment in Parkinson’s Disease

Context: Cognitive impairments are common in patients with Parkinson’s disease (PD) and are heterogeneous in their presentation. The “dual syndrome hypothesis” suggests the existence of two distinct subtypes of mild cognitive impairment (MCI) in PD: a frontostriatal subtype with predominant attentional and/or executive deficits and a posterior cortical subtype with predominant visuospatial, memory, and/or language deficits. The latter subtype has been associated with a higher risk of developing dementia.Objective: The objective of this study was to identify structural modifications in cortical and subcortical regions associated with each PD-MCI subtype.Methods: One-hundred and fourteen non-demented PD patients underwent a comprehensive neuropsychological assessment as well as a 3T magnetic resonance imaging scan. Patients were categorized as having no cognitive impairment (n = 41) or as having a frontostriatal (n = 16), posterior cortical (n = 25), or a mixed (n = 32) MCI subtype. Cortical regions were analyzed using a surface-based Cortical thickness (CTh) method. In addition, the volumes, shapes, and textures of the caudate nuclei, hippocampi, and thalami were studied. Tractometric analyses were performed on associative and commissural white matter (WM) tracts.Results: There were no between-group differences in volumetric measurements and cortical thickness. Shape analyses revealed more abundant and more extensive deformations fields in the caudate nuclei, hippocampi, and thalami in patients with posterior cortical deficits compared to patients with no cognitive impairment. Decreased fractional anisotropy (FA) and increased mean diffusivity (MD) were also observed in the superior longitudinal fascicle, the inferior fronto-occipital fascicle, the striato-parietal tract, and the anterior and posterior commissural tracts. Texture analyses showed a significant difference in the right hippocampus of patients with a mixed MCI subtype.Conclusion: PD-MCI patients with posterior cortical deficits have more abundant and more extensive structural alterations independently of age, disease duration, and severity, which may explain why they have an increased risk of dementia.

Quantity and quality: Normative open-access neuroimaging databases

The focus of this article is to compare twenty normative and open-access neuroimaging databases based on quantitative measures of image quality, namely, signal-to-noise (SNR) and contrast-to-noise ratios (CNR). We further the analysis through discussing to what extent these databases can be used for the visualization of deeper regions of the brain, such as the subcortex, as well as provide an overview of the types of inferences that can be drawn. A quantitative comparison of contrasts including T1-weighted (T1w) and T2-weighted (T2w) images are summarized, providing evidence for the benefit of ultra-high field MRI. Our analysis suggests a decline in SNR in the caudate nuclei with increasing age, in T1w, T2w, qT1 and qT2* contrasts, potentially indicative of complex structural age-dependent changes. A similar decline was found in the corpus callosum of the T1w, qT1 and qT2* contrasts, though this relationship is not as extensive as within the caudate nuclei. These declines were accompanied by a declining CNR over age in all image contrasts. A positive correlation was found between scan time and the estimated SNR as well as a negative correlation between scan time and spatial resolution. Image quality as well as the number and types of contrasts acquired by these databases are important factors to take into account when selecting structural data for reuse. This article highlights the opportunities and pitfalls associated with sampling existing databases, and provides a quantitative backing for their usage.