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Despite decades of research, the pathophysiology of bipolar disorder (BD) is still not well understood. Structural brain differences have been associated with BD, but results from neuroimaging studies have been inconsistent. To address this, we performed the largest study to date of cortical gray matter thickness and surface area measures from brain magnetic resonance imaging scans of 6503 individuals including 1837 unrelated adults with BD and 2582 unrelated healthy controls for group differences while also examining the effects of commonly prescribed medications, age of illness onset, history of psychosis, mood state, age and sex differences on cortical regions. In BD, cortical gray matter was thinner in frontal, temporal and parietal regions of both brain hemispheres. BD had the strongest effects on left pars opercularis (Cohen's d=-0.293; P=1.71 × 10-21), left fusiform gyrus (d=-0.288; P=8.25 × 10-21) and left rostral middle frontal cortex (d=-0.276; P=2.99 × 10-19). Longer duration of illness (after accounting for age at the time of scanning) was associated with reduced cortical thickness in frontal, medial parietal and occipital regions. We found that several commonly prescribed medications, including lithium, antiepileptic and antipsychotic treatment showed significant associations with cortical thickness and surface area, even after accounting for patients who received multiple medications. We found evidence of reduced cortical surface area associated with a history of psychosis but no associations with mood state at the time of scanning. Our analysis revealed previously undetected associations and provides an extensive analysis of potential confounding variables in neuroimaging studies of BD.

Multiple sclerosis (MS) is the most common acquired inflammatory and demyelinating disease in adults. The conventional diagnostic of MS and the follow-up of inflammatory activity is based on the detection of hyperintense foci in T2 and fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) and lesions with brain-blood barrier (BBB) disruption in the central nervous system (CNS) parenchyma. However, T2/FLAIR hyperintense lesions are not specific to MS and the MS pathology and inflammatory processes go far beyond focal lesions and can be independent of BBB disruption. MRI techniques based on the magnetic susceptibility properties of the tissue, such as T2*, susceptibility-weighted images (SWI), and quantitative susceptibility mapping (QSM) offer tools for advanced MS diagnostic, follow-up, and the assessment of more detailed features of MS dynamic pathology. Susceptibility-weighted techniques are sensitive to the paramagnetic components of biological tissues, such as deoxyhemoglobin. This capability enables the visualization of brain parenchymal veins. Consequently, it presents an opportunity to identify veins within the core of multiple sclerosis (MS) lesions, thereby affirming their venocentric characteristics. This advancement significantly enhances the accuracy of the differential diagnostic process. Another important paramagnetic component in biological tissues is iron. In MS, the dynamic trafficking of iron between different cells, such as oligodendrocytes, astrocytes, and microglia, enables the study of different stages of demyelination and remyelination. Furthermore, the accumulation of iron in activated microglia serves as an indicator of latent inflammatory activity in chronic MS lesions, termed paramagnetic rim lesions (PRLs). PRLs have been correlated with disease progression and degenerative processes, underscoring their significance in MS pathology. This review will elucidate the underlying physical principles of magnetic susceptibility and their implications for the formation and interpretation of T2*, SWI, and QSM sequences. Additionally, it will explore their applications in multiple sclerosis (MS), particularly in detecting the central vein sign (CVS) and PRLs, and assessing iron metabolism. Furthermore, the review will discuss their role in advancing early and precise MS diagnosis and prognostic evaluation, as well as their utility in studying chronic active inflammation and degenerative processes.

Objective: To investigate the association between left epileptiform activity and language laterality indices (LI) in patients with right mesial temporal sclerosis (MTS)., Methods: Twenty-two patients with right MTS and 22 healthy subjects underwent fMRI scanning while performing a language task. LI was calculated in multiple regions of interest (ROI). Data on the presence of left epileptiform abnormalities were obtained during prolonged video-EEG monitoring., Results: After correction for multiple comparisons, LI was reduced in the middle temporal gyrus in the left interictal epileptiform discharges (IED+) group, compared with the left IED- group (p < 0.05)., Significance: Using a responsive reading naming fMRI paradigm, right MTS patients who presented left temporal interictal epileptiform abnormalities on video-EEG showed decreased LI in the middle temporal gyrus, indicating decreased left middle temporal gyrus activation, increased right middle temporal gyrus activation or a combination of both, demonstrative of language network reorganization, specially in the MTG, in this patient population., Plain Language Summary: This research studied 22 patients with right mesial temporal sclerosis (a specific type of epilepsy) comparing them to 22 healthy individuals. Participants were asked to perform a language task while undergoing a special brain imaging technique (fMRI). The findings showed that patients with epilepsy displayed a change in the area of the brain typically responsible for language processing. This suggests that their brains may have adapted due to their condition, altering the way language is processed., (© 2024 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Nanostructured contrast agents are promising alternatives to Gd 3+ -based chelates in magnetic resonance (MR) imaging techniques. A novel ultrasmall paramagnetic nanoparticle (UPN) was strategically designed to maximize the number of exposed paramagnetic sites and r 1 while minimizing r 2 , by decorating 3 nm titanium dioxide nanoparticles with suitable amounts of iron oxide. Its relaxometric parameters are comparable to those of gadoteric acid (GA) in agar phantoms, and the r 2 / r 1 ratio of 1.38 at 3 T is close to the ideal unitary value. The strong and prolonged contrast enhancement of UPN before renal excretion was confirmed by T 1 -weighted MR images of Wistar rats after intravenous bolus injection. Those results associated with good biocompatibility indicate its high potential as an alternative blood-pool contrast agent to the GA gold standard for MR angiography, especially for patients with severe renal impairment.

Quantitative Susceptibility Mapping (QSM) is an established Magnetic Resonance Imaging (MRI) technique with high potential in brain iron studies associated to several neurodegenerative diseases. Unlike other MRI techniques, QSM relies on phase images to estimate tissue's relative susceptibility, therefore requiring a reliable phase data. Phase images from a multi-channel acquisition should be reconstructed in a proper way. On this work it was compared the performance of combination of phase matching algorithms (MCPC3D-S and VRC) and phase combination methods based on a complex weighted sum of phases, considering the magnitude at different powers ( k = 0 to 4) as the weighting factor. These reconstruction methods were applied in two datasets: a simulated brain dataset for a 4-coil array and data of 22 postmortem subjects acquired at a 7T scanner using a 32 channels coil. For the simulated dataset, differences between the ground truth and the Root Mean Squared Error (RMSE) were evaluated. For both simulated and postmortem data, the mean (MS) and standard deviation (SD) of susceptibility values of five deep gray matter regions were calculated. For the postmortem subjects, MS and SD were statistically compared across all subjects. A qualitative analysis indicated no differences between methods, except for the Adaptive approach on postmortem data, which showed intense artifacts. In the 20% noise level case, the simulated data showed increased noise in central regions. Quantitative analysis showed that both MS and SD were not statistically different when comparing k = 1 and k = 2 on postmortem brain images, however visual inspection showed some boundaries artifacts on k = 2. Furthermore, the RMSE decreased (on regions near the coils) and increased (on central regions and on overall QSM) with increasing k . In conclusion, for reconstruction of phase images from multiple coils with no reference available, alternative methods are needed. In this study it was found that overall, the phase combination with k = 1 is preferred over other powers of k ., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Background and Purpose: Superagers are defined as older adults with episodic memory performance similar or superior to that in middle-aged adults. This study aimed to investigate the key differences in discriminative networks and their main nodes between superagers and cognitively average elderly controls. In addition, we sought to explore differences in sensitivity in detecting these functional activities across the networks at 3T and 7T MR imaging fields., Materials and Methods: Fifty-five subjects 80 years of age or older were screened using a detailed neuropsychological protocol, and 31 participants, comprising 14 superagers and 17 cognitively average elderly controls, were included for analysis. Participants underwent resting-state-fMRI at 3T and 7T MR imaging. A prediction classification algorithm using a penalized regression model on the measurements of the network was used to calculate the probabilities of a healthy older adult being a superager. Additionally, ORs quantified the influence of each node across preselected networks., Results: The key networks that differentiated superagers and elderly controls were the default mode, salience, and language networks. The most discriminative nodes (ORs > 1) in superagers encompassed areas in the precuneus posterior cingulate cortex, prefrontal cortex, temporoparietal junction, temporal pole, extrastriate superior cortex, and insula. The prediction classification model for being a superager showed better performance using the 7T compared with 3T resting-state-fMRI data set., Conclusions: Our findings suggest that the functional connectivity in the default mode, salience, and language networks can provide potential imaging biomarkers for predicting superagers. The 7T field holds promise for the most appropriate study setting to accurately detect the functional connectivity patterns in superagers., (© 2023 by American Journal of Neuroradiology.)

Purpose: A method named DECOMPOSE-QSM is developed to decompose bulk susceptibility measured with QSM into sub-voxel paramagnetic and diamagnetic components based on a three-pool complex signal model., Methods: Multi-echo gradient echo signal is modeled as a summation of three weighted exponentials corresponding to three types of susceptibility sources: reference susceptibility, diamagnetic and paramagnetic susceptibility relative to the reference. Paramagnetic component susceptibility (PCS) and diamagnetic component susceptibility (DCS) maps are constructed to represent the sub-voxel compartments by solving for linear and nonlinear parameters in the model., Results: Numerical forward simulation and phantom validation confirmed the ability of DECOMPOSE-QSM to separate the mixture of paramagnetic and diamagnetic components. The PCS obtained from temperature-variant brainstem imaging follows the Curie's Law, which further validated the model and the solver. Initial in vivo investigation of human brain images showed the ability to extract sub-voxel PCS and DCS sources that produce visually enhanced contrast between brain structures comparing to threshold QSM., (Copyright © 2021. Published by Elsevier Inc.)

Background and Purpose: Among several cognitive advantages, meditation is thought to enhance practitioners' capacity for sustained attention. In the present study, we explored this question by testing meditation practitioners (meditators) and nonpractitioners (nonmeditators) on a task that requires sustained attention, the Stroop Word-Color Task (SWCT), while using functional MRI., Participants and Methods: Participants were all right-handed and included 23 regular meditators as well as 17 nonmeditators. Participants viewed color words (i.e. 'red,' 'blue,' or 'green') presented one at a time on the screen that were written in either the same color (congruent condition) or a different color (incongruent condition) and were asked to indicate the color of the print. Participants also viewed noncolor words written in unrelated colors (neutral condition). Both groups completed the same two acquisition runs., Results: Although both meditators and nonmeditators gave faster responses on run 2 than run 1 for both the neutral and incongruent trials, nonmeditators showed decreased activation and meditators showed increased activation in precuneus/posterior cingulate cortex. These regions were previously shown to be activated in the SWCT and belong to default mode network as well as to cognitive control network., Conclusion: Attention to repetitive stimuli during two equal runs of SWCT is mediated by the precuneus/posterior cingulate cortex, and mental training through meditation may influence the activity of these regions during such tasks.

Meditation as a cognitive enhancement technique is of growing interest in the field of health and research on brain function. The Stroop Word-Color Task (SWCT) has been adapted for neuroimaging studies as an interesting paradigm for the understanding of cognitive control mechanisms. Performance in the SWCT requires both attention and impulse control, which is trained in meditation practices. We presented SWCT inside the MRI equipment to measure the performance of meditators compared with non-meditators before and after a meditation retreat. The aim of this study was to evaluate the effects of a 7-day Zen intensive meditation training (a retreat) on meditators and non-meditators in this task on performance level and neural mechanisms. Nineteen meditators and 14 non-meditators were scanned before and after a 7-day Zen meditation retreat. No significant differences were found between meditators and non-meditators in the number of the correct responses and response time (RT) during SWCT before and after the retreat. Probably, due to meditators training in attention, their brain activity in the contrast incongruent > neutral during the SWCT in the anterior cingulate, ventromedial prefrontal cortex/anterior cingulate, caudate/putamen/pallidum/temporal lobe (center), insula/putamen/temporal lobe (right) and posterior cingulate before the retreat, were reduced compared with non-meditators. After the meditation retreat, non-meditators had reduced activation in these regions, becoming similar to meditators before the retreat. This result could be interpreted as an increase in the brain efficiency of non-meditators (less brain activation in attention-related regions and same behavioral response) promoted by their intensive training in meditation in only 7 days. On the other hand, meditators showed an increase in brain activation in these regions after the same training. Intensive meditation training (retreat) presented distinct effects on the attention-related regions in meditators and non-meditators probably due to differences in expertise, attention processing as well as neuroplasticity.

Objectives: To detect by diffusion tensor imaging (DTI) the extent of microstructural integrity changes of the corpus callosum (CC) in patients with hippocampal sclerosis (HS) and to evaluate possible association with clinical characteristics., Methods: Fourty-two patients with temporal lobe epilepsy (TLE) and HS and 30 control subjects were studied with DTI. We grouped patients according to lesion side (left or right) HS. Mean diffusivity (MD), fractional anisotropy (FA), radial (RD) and axial diffusivity (AD) were extracted from five segments in CC midsagittal section obtained by automatic segmentation. CC DTI findings were compared between groups. We also evaluated association of DTI changes and clinical characteristics., Results: HS patients displayed decreased FA and increased MD and RD in the anterior, mid-posterior and posterior CC segments, compared to controls. No differences were observed in AD. Patients reporting febrile seizure as the initial precipitating event presented more intense diffusion changes. No differences were seen comparing left and right HS. Age at epilepsy onset, disease duration and seizure frequency were not associated with DTI findings., Conclusions: This is one of the largest series of TLE-HS patients evaluating CC white matter fiber integrity by DTI, which allowed us to study how some clinical characteristics, such as seizure frequency, disease duration and lesion side, are related to CC integrity. Occurrence of febrile seizure was the only factor that had significant impact on tract integrity. Diffusion changes were not restricted to the posterior part of the CC; we observed the same changes for the anterior part of the CC. Diffusion changes were characterized by an increase in RD, while the AD remained intact for all regions of the CC., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objectives: Our goal was to estimate the diagnostic accuracy of substantia nigra fractional anisotropy (SN-FA) for Parkinson's disease (PD) diagnosis in a sample similar to the clinical setting, including patients with essential tremor (ET) and healthy controls (HC). We also performed a systematic review and meta-analysis to estimate mean change in SN-FA induced by PD and its diagnostic accuracy., Methods: Our sample consisted of 135 subjects: 72 PD, 21 ET and 42 HC. To address inter-scanner variability, two 3.0-T MRI scans were performed. MRI results of this sample were pooled into a meta-analysis that included 1,432 subjects (806 PD and 626 HC). A bivariate model was used to evaluate diagnostic accuracy measures., Results: In our sample, we did not observe a significant effect of disease on SN-FA and it was uninformative for diagnosis. The results of the meta-analysis estimated a 0.03 decrease in mean SN-FA in PD relative to HC (CI: 0.01-0.05). However, the discriminatory capability of SN-FA to diagnose PD was low: pooled sensitivity and specificity were 72 % (CI: 68-75) and 63 % (CI: 58-70), respectively. There was high heterogeneity between studies (I 2  = 91.9 %)., Conclusions: SN-FA cannot be used as an isolated measure to diagnose PD., Key Points: • SN-FA appears insufficiently sensitive and specific to diagnose PD. • Radiologists must be careful when translating mean group results to clinical practice. • Imaging protocol and analysis standardization is necessary for developing reproducible quantitative biomarkers.

Objective: To assess changes in blood-oxygen-level-dependent activity after light deprivation compared to regular light exposure in subjects with migraine in the interictal state and in controls., Methods: Ten subjects with migraine and ten controls participated in two sessions of functional magnetic resonance imaging. In each session, they performed a finger-tapping task with the right hand, cued by visual stimuli. They were scanned before and after 30 minutes of light deprivation or light exposure. In subjects with migraine, functional magnetic resonance imaging was performed interictally. Analysis of variance was made with the factors time (before or after), session (light deprivation or exposure), and group (migraine or control)., Results: There were significant "group" effects in a cluster in the bilateral cuneus encompassing the superior border of the calcarine sulcus and extrastriate cortex. There were no significant effects of "time", "session", or interactions between these factors., Conclusion: The main result of this study is consistent with aberrant interictal processing of visual information in migraine. Light deprivation did not modulate functional magnetic resonance imaging activity in subjects with or without migraine., Objetivo: Avaliar mudanças na atividade cerebral por meio de ressonância magnética funcional após privação luminosa comparada à exposição à luz, em indivíduos com enxaqueca no estado interictal e em controles., Métodos: Dez indivíduos com enxaqueca e dez controles participaram de duas sessões de ressonância magnética funcional. Em cada sessão, realizaram uma tarefa motora com a mão direita guiada por estímulos visuais. Foram colhidas imagens antes e após 30 minutos de privação luminosa ou exposição à luz. Em indivíduos com enxaqueca, a ressonância funcional foi realizada no período interictal. Foi feita a análise de variância com fatores tempo (antes ou depois), sessão (privação ou exposição à luz) e grupo (enxaqueca ou controle)., Resultados: Houve efeitos significativos de "grupo" em uma área no cúneo bilateral, incluindo a borda superior do sulco calcarino e o córtex extraestriado. Não houve efeitos significativos de "tempo", "sessão" ou interações entre estes fatores., Conclusão: O principal resultado deste estudo sugere um processamento interictal anormal das informações visuais em indivíduos com enxaqueca. A privação luminosa não modulou a atividade na ressonância magnética funcional em indivíduos com ou sem enxaqueca.

The updating of prospective internal models is necessary to accurately predict future observations. Uncertainty-driven internal model updating has been studied using a variety of perceptual paradigms, and have revealed engagement of frontal and parietal areas. In a distinct literature, studies on temporal expectations have also characterized a time-perception network, which relies on temporal orienting of attention. However, the updating of prospective internal models is highly dependent on temporal attention, since temporal attention must be reoriented according to the current environmental demands. In this study, we used functional magnetic resonance imaging (fMRI) to evaluate to what extend the continuous manipulation of temporal prediction would recruit update-related areas and the time-perception network areas. We developed an exogenous temporal task that combines rhythm cueing and time-to-contact principles to generate implicit temporal expectation. Two patterns of motion were created: periodic (simple harmonic oscillation) and non-periodic (harmonic oscillation with variable acceleration). We found that non-periodic motion engaged the exogenous temporal orienting network, which includes the ventral premotor and inferior parietal cortices, and the cerebellum, as well as the presupplementary motor area, which has previously been implicated in internal model updating, and the motion-sensitive area MT+. Interestingly, we found a right-hemisphere preponderance suggesting the engagement of explicit timing mechanisms. We also show that the periodic motion condition, when compared to the non-periodic motion, activated a particular subset of the default-mode network (DMN) midline areas, including the left dorsomedial prefrontal cortex (DMPFC), anterior cingulate cortex (ACC), and bilateral posterior cingulate cortex/precuneus (PCC/PC). It suggests that the DMN plays a role in processing contextually expected information and supports recent evidence that the DMN may reflect the validation of prospective internal models and predictive control. Taken together, our findings suggest that continuous manipulation of temporal predictions engages representations of temporal prediction as well as task-independent updating of internal models.

Purpose: To evaluate the functional magnetic resonance imaging (fMRI) response to binocular visual stimulation and the association thereof with structural ocular findings and psychophysical test results in patients with glaucoma, and controls., Methods: Cross-sectional study. Participants underwent a complete ophthalmic examination, including Humphrey 24-2 visual field (VF) testing and optical coherence tomography. Binocular VF in each quadrant was determined using an integrated method. Patients with glaucoma were assigned to three subgroups: initial, asymmetrical and severe glaucoma. Regions of interest (ROIs) were determined anatomically. fMRI (3 T) was performed using a bilaterally presented polar angle stimulus, and the accompanying changes in blood oxygen level-dependent (BOLD) signals were obtained from the occipital poles and calcarine ROIs. We used generalized estimation equation models to compare anatomical and functional data between the groups., Results: A total of 25 subjects were enrolled, of whom 17 had glaucoma and 8 were controls. Significant associations between quadrant binocular VF sensitivities and fMRI responses were found in the occipital pole ROIs (p = 0.033) and the calcarine ROIs (p = 0.045). In glaucoma severity subgroup analysis, retinal nerve fiber layer (RNFL) thickness was associated with the BOLD response of the calcarine and occipital pole ROIs (p = 0.002 and 0.026, respectively). The initial and asymmetrical glaucoma subgroups had similar binocular VF sensitivities and RNFL thicknesses, but distinct BOLD responses., Conclusions: The response of the visual cortex to binocular stimulation was associated with binocular VF sensitivity. RNFL thickness was associated with the BOLD response of the calcarine and occipital pole ROIs.

B-cell lymphoma 2 (Bcl-2) is an important regulator of cellular plasticity and resilience. In bipolar disorder (BD), studies have shown a key role for a Bcl-2 gene single-nucleotide polymorphism (SNP) rs956572 in the regulation of intracellular calcium (Ca(2+)) dynamics, Bcl-2 expression/levels, and vulnerability to cellular apoptosis. At the same time, Bcl-2 decreases glutamate (Glu) toxicity in neural cells. Abnormalities in Glu function have been implicated in BD. In magnetic resonance spectroscopy (MRS) studies, anterior cingulated cortex (ACC) Glu levels have been reported to be increased in bipolar depression and mania, but no study specifically evaluated ACC Glu levels in BD-euthymia. Here, we compared ACC Glu levels in BD-euthymia compared with healthy subjects using (1)H-MRS and also evaluated the selective role of the rs956572 Bcl-2 SNP in modulating ACC Glu and Glx (sum of Glu and glutamine) in euthymic-BD. Forty euthymic subjects with BD type I and forty healthy controls aged 18-40 were evaluated. All participants were genotyped for Bcl-2 rs956572 and underwent a 3-Tesla brain magnetic resonance imaging examination including the acquisition of an in vivo PRESS single voxel (2 cm(3)) (1)H-MRS sequence to obtain metabolite levels from the ACC. Euthymic-BD subjects had higher Glu/Cre (creatine) and Glx/Cre compared with healthy controls. The Bcl-2 SNP AA genotype was associated with elevated ACC Glu/Cre and Glx/Cre ratio in the BD group but not in controls. The present study reports for the first time an increase in ACC Glu/Cre and Glx/Cre ratios in BD-euthymia. Also, Bcl-2 AA genotype, previously associated with lower Bcl-2 expression and increase intracellular Ca(2+), showed to be associated with increased ACC Glu and Glx levels in euthymic-BD subjects. The present findings reinforce a key role for glutamatergic system dysfunction in the pathophysiology of BD, potentially involving modulatory effects by Bcl-2 in the ACC.