Alan Tucholka

Neurofeedback Training Induces Changes in White and Gray Matter

The main objective of this structural magnetic resonance imaging (MRI) study was to investigate, using diffusion tensor imaging, whether a neurofeedback training (NFT) protocol designed to improve sustained attention might induce structural changes in white matter (WM) pathways, purportedly implicated in this cognitive ability. Another goal was to examine whether gray matter (GM) volume (GMV) might be altered following NFT in frontal and parietal cortical areas connected by these WM fiber pathways. Healthy university students were randomly assigned to an experimental group (EXP), a sham group, or a control group. Participants in the EXP group were trained to enhance the amplitude of their β1 waves at F4 and P4. Measures of attentional performance and MRI data were acquired one week before (Time 1) and one week after (Time 2) NFT. Higher scores on visual and auditory sustained attention were noted in the EXP group at Time 2 (relative to Time 1). As for structural MRI data, increased fractional anisotropy was measured in WM pathways implicated in sustained attention, and GMV increases were detected in cerebral structures involved in this type of attention. After 50 years of research in the field of neurofeedback, our study constitutes the first empirical demonstration that NFT can lead to microstructural changes in white and gray matter.

The Corticocortical Structural Connectivity of the Human Insula

Abstract The insula is a complex structure involved in a wide range of functions. Tracing studies on nonhuman primates reveal a wide array of cortical connections in the frontal (orbitofrontal and prefrontal cortices, cingulate areas and supplementary motor area), parietal (primary and secondary somatosensory cortices) and temporal (temporal pole, auditory, prorhinal and entorhinal cortices) lobes. However, recent human tractography studies have not observed connections between the insula and the cingulate cortices, although these structures are thought to be functionally intimately connected. In this work, we try to unravel the structural connectivity between these regions and other known functionally connected structures, benefiting from a higher number of subjects and the latest state‐of‐the‐art high angular resolution diffusion imaging (HARDI) tractography algorithms with anatomical priors. By performing an HARDI tractography analysis on 46 young normal adults, our study reveals a wide array of connections between the insula and the frontal, temporal, parietal and occipital lobes as well as limbic regions, with a rostro‐caudal organization in line with tracing studies in macaques. Notably, we reveal for the first time in humans a clear structural connectivity between the insula and the cingulate, parahippocampal, supramarginal and angular gyri as well as the precuneus and occipital regions.

Nonlinear cerebral atrophy patterns across the Alzheimer's disease continuum: impact of APOE4 genotype

The progression of Alzheimers disease (AD) is characterized by complex trajectories of cerebral atrophy that are affected by interactions with age and apolipoprotein E allele ε4 (APOE4) status. In this article, we report the nonlinear volumetric changes in gray matter across the full biological spectrum of the disease, represented by the AD-cerebrospinal fluid (CSF) index. This index reflects the subjects level of pathology and position along the AD continuum. We also evaluated the associated impact of the APOE4 genotype. The atrophy pattern associated with the AD-CSF index was highly symmetrical and corresponded with the typical AD signature. Medial temporal structures showed different atrophy dynamics along the progression of the disease. The bilateral parahippocampal cortices and a parietotemporal region extending from the middle temporal to the supramarginal gyrus presented an initial increase in volume which later reverted. Similarly, a portion of the precuneus presented a rather linear inverse association with the AD-CSF index whereas some other clusters did not show significant atrophy until index values corresponded to positive CSF tau values. APOE4 carriers showed steeper hippocampal volume reductions with AD progression. Overall, the reported atrophy patterns are in close agreement with those mentioned in previous findings. However, the detected nonlinearities suggest that there may be different pathological processes taking place at specific moments during AD progression and reveal the impact of the APOE4 allele.

CEREBROSPINAL FLUID STREM2 LEVELS ARE ASSOCIATED WITH GRAY MATTER VOLUME INCREASES AND REDUCED DIFFUSIVITY IN EARLY ALZHEIMER’S DISEASE

TREM2 is involved in the regulation of inflammatory response and phagocytosis. A soluble fragment (sTREM2) is often found abnormally increased in cerebrospinal fluid (CSF) in Alzheimers disease (AD).

CSF YKL-40 and pTau181 are related to different cerebral morphometric patterns in early AD.

Cerebrospinal fluid (CSF) concentrations of YKL-40 that serve as biomarker of neuroinflammation are known to be altered along the clinico-biological continuum of Alzheimers disease (AD). The specific structural cerebral correlates of CSF YKL-40 were evaluated across the early stages of AD from normal to preclinical to mild dementia. Nonlinear gray matter (GM) volume associations with CSF YKL-40 levels were assessed in a total of 116 subjects, including normal controls and those with preclinical AD as defined by CSF Aβ < 500 pg/mL, mild cognitive impairment (MCI) due to AD, or mild AD dementia. Age-corrected YKL-40 levels were increased in MCIs versus the rest of groups and showed an inverse u-shaped association with p-tau values. A similar nonlinear relationship was found between GM volume and YKL-40 in inferior and lateral temporal regions spreading to the supramarginal gyrus, insula, inferior frontal cortex, and cerebellum in MCI and AD. These findings for YKL-40 remained unchanged after adjusting for p-tau, which was found to be associated with GM volumes in distinct anatomic areas. CSF YKL-40, a biomarker of glial inflammation, is associated with a cerebral structural signature distinct from that related to p-tau neurodegeneration at the earliest stages of cognitive decline due to AD.

MRI pallidal signal in children exposed to manganese in drinking water

BACKGROUND Manganese (Mn) can have neurotoxic effects upon overexposure. We previously reported poorer cognitive and motor development in children exposed to Mn through drinking water, suggesting possible neurotoxic effects from Mn in water. Hyperintensity in the globus pallidus (GP) on T1-weighted magnetic resonance imaging (MRI) indicates excessive brain Mn accumulation. Previous studies have reported GP hyperintensity related to Mn exposure in occupationally exposed individuals. However, no study has used MRI in children exposed to Mn in drinking water and who show no sign of overt intoxication. OBJECTIVE To examine MRI signal intensity in the GP in children exposed to contrasted levels of Mn in drinking water. METHODS We enrolled 13 children exposed to low Mn concentration in water and 10 children (ages 9-15 years) with high concentration (median of 1 and 145μg/L, respectively). We calculated three MRI T1 indexes: (i) standard pallidal index (PI) using frontal white matter as reference; (ii) PI using pericranial muscles as reference; and (iii) T1 relaxation time. Each MRI index was compared between exposure groups, and with respect to the estimated Mn intake from water consumption. RESULTS The standard PI did not differ between Mn-exposure groups. However, children in the group with high water-Mn concentration had significantly lower pericranial muscles PI than those with lower exposure and, accordingly, higher T1 relaxation time. Mn intake from water consumption was not correlated with the standard PI, but was significantly related to the pericranial muscles PI and T1 relaxation time. Motor performance was significantly lower in the high-exposure group. CONCLUSION We observed lower signal intensity in the GP of children with higher exposure to Mn from drinking water. This result stands in contrast to previous MRI reports showing GP hyperintensity with greater Mn exposure. Differences in exposure pathways are discussed as a potential explanation for this discrepancy.

Multisite evaluations of a T2‐relaxation‐under‐spin‐tagging (TRUST) MRI technique to measure brain oxygenation

Venous oxygenation (Yv) is an important index of brain physiology and may be indicative of brain diseases. A T2‐relaxation‐under‐spin‐tagging (TRUST) MRI technique was recently developed to measure Yv. A multisite evaluation of this technique would be an important step toward broader availability and potential clinical utilizations of Yv measures.

A whole-brain computational modeling approach to explain the alterations in resting-state functional connectivity during progression of Alzheimer's disease

Alzheimers disease (AD) is the most common dementia with dramatic consequences. The research in structural and functional neuroimaging showed altered brain connectivity in AD. In this study, we investigated the whole-brain resting state functional connectivity (FC) of the subjects with preclinical Alzheimers disease (PAD), mild cognitive impairment due to AD (MCI) and mild dementia due to Alzheimers disease (AD), the impact of APOE4 carriership, as well as in relation to variations in core AD CSF biomarkers. The synchronization in the whole-brain was monotonously decreasing during the course of the disease progression. Furthermore, in AD patients we found widespread significant decreases in functional connectivity (FC) strengths particularly in the brain regions with high global connectivity. We employed a whole-brain computational modeling approach to study the mechanisms underlying these alterations. To characterize the causal interactions between brain regions, we estimated the effective connectivity (EC) in the model. We found that the significant EC differences in AD were primarily located in left temporal lobe. Then, we systematically manipulated the underlying dynamics of the model to investigate simulated changes in FC based on the healthy control subjects. Furthermore, we found distinct patterns involving CSF biomarkers of amyloid-beta (Aβ1 − 42) total tau (t-tau) and phosphorylated tau (p-tau). CSF Aβ1 − 42 was associated to the contrast between healthy control subjects and clinical groups. Nevertheless, tau CSF biomarkers were associated to the variability in whole-brain synchronization and sensory integration regions. These associations were robust across clinical groups, unlike the associations that were found for CSF Aβ1 − 42. APOE4 carriership showed no significant correlations with the connectivity measures.

The APOE ε4 genotype modulates CSF YKL-40 levels and their structural brain correlates in the continuum of Alzheimer's disease but not those of sTREM2

Among other metabolic functions, the apolipoprotein E (APOE) plays a crucial role in neuroinflammation. We aimed at assessing whether APOE ε4 modulates levels of glial cerebrospinal fluid (CSF) biomarkers and their structural cerebral correlates along the continuum of Alzheimers disease (AD).

Statistical shape analysis of subcortical structures using spectral matching

Studying morphological changes of subcortical structures often predicate neurodevelopmental and neurodegenerative diseases, such as Alzheimers disease and schizophrenia. Hence, methods for quantifying morphological variations in the brain anatomy, including groupwise shape analyses, are becoming increasingly important for studying neurological disorders. In this paper, a novel groupwise shape analysis approach is proposed to detect regional morphological alterations in subcortical structures between two study groups, e.g., healthy and pathological subjects. The proposed scheme extracts smoothed triangulated surface meshes from segmented binary maps, and establishes reliable point-to-point correspondences among the population of surfaces using a spectral matching method. Mean curvature features are incorporated in the matching process, in order to increase the accuracy of the established surface correspondence. The mean shapes are created as the geometric mean of all surfaces in each group, and a distance map between these shapes is used to characterize the morphological changes between the two study groups. The resulting distance map is further analyzed to check for statistically significant differences between two populations. The performance of the proposed framework is evaluated on two separate subcortical structures (hippocampus and putamen). Furthermore, the proposed methodology is validated in a clinical application for detecting abnormal subcortical shape variations in Alzheimers disease. Experimental results show that the proposed method is comparable to state-of-the-art algorithms, has less computational cost, and is more sensitive to small morphological variations in patients with neuropathologies.