Multi-Contrast Magnetic Resonance Imaging of Visual White Matter Pathways in Patients With Glaucoma.

Purpose: Glaucoma is a disorder that involves visual field loss caused by retinal ganglion cell damage. Previous diffusion magnetic resonance imaging (dMRI) studies have demonstrated that retinal ganglion cell damage affects tissues in the optic tract (OT) and optic radiation (OR). However, because previous studies have used a simple diffusion tensor model to analyze dMRI data, the microstructural interpretation of white matter tissue changes remains uncertain. In this study, we used a multi-contrast MRI approach to further clarify the type of microstructural damage that occurs in patients with glaucoma. Methods: We collected dMRI data from 17 patients with glaucoma and 30 controls using 3-tesla (3T) MRI. Using the dMRI data, we estimated three types of tissue property metrics: intracellular volume fraction (ICVF), orientation dispersion index (ODI), and isotropic volume fraction (IsoV). Quantitative T1 (qT1) data, which may be relatively specific to myelin, were collected from all subjects. Results: In the OT, all four metrics showed significant differences between the glaucoma and control groups. In the OR, only the ICVF showed significant between-group differences. ICVF was significantly correlated with qT1 in the OR of the glaucoma group, although qT1 did not show any abnormality at the group level. Conclusions: Our results suggest that, at the group level, tissue changes in OR caused by glaucoma might be explained by axonal damage, which is reflected in the intracellular diffusion signals, rather than myelin damage. The significant correlation between ICVF and qT1 suggests that myelin damage might also occur in a smaller number of severe cases.

Disrupted Dynamic Functional Connectivity of the Visual Network in Episodic Patients with Migraine without Aura.

Background: Visual symptoms are common in patients with migraine, even in interictal periods. The purpose was to assess the association between dynamic functional connectivity (dFC) of the visual cortex and clinical characteristics in migraine without aura (MwoA) patients. Methods: We enrolled fifty-five MwoA patients as well as fifty gender- and age-matched healthy controls. Regional visual cortex alterations were investigated using regional homogeneity (ReHo) and amplitude of low-frequency fluctuation (ALFF). Then, significant regions were selected as seeds for conducting dFC between the visual cortex and the whole brain. Results: Relative to healthy controls, MwoA patients exhibited decreased ReHo and ALFF values in the right lingual gyrus (LG) and increased ALFF values in the prefrontal cortex. The right LG showed abnormal dFC within the visual cortex and with other core brain networks. Additionally, ReHo values for the right LG were correlated with duration of disease and ALFF values of the right inferior frontal gyrus and middle frontal gyrus were correlated with headache frequency and anxiety scores, respectively. Moreover, the abnormal dFC of the right LG with bilateral cuneus was positively correlated with anxiety scores. Conclusions: The dFC abnormalities of the visual cortex may be involved in pain integration with multinetworks and associated with anxiety disorder in episodic MwoA patients.

Impaired P100 among regular cannabis users in response to magnocellular biased visual stimuli.

Regular cannabis using causes vision impairment by affecting human retinal neurotransmission. However, studies less considered its impact on the subsequent visual cortical processing, key feature for the integration of the visual signal in brain. We aimed at investigating this purpose in regular cannabis users using spatial frequencies and temporal frequencies filtered visual stimuli. We recruited 45 regular cannabis users and 25 age-matched controls. We recorded visual evoked potentials during the projection of low spatial frequency (0.5 cycles/degree) or high spatial frequency gratings (15 cycles/degree), which were presented statically (0 Hz) or dynamically (8 Hz). We analyzed the amplitude, latency, and area under the curve of both P100 and N170, best EEG markers for early visual processing. Data were compared between groups by repeated measures ANCOVA. Results showed a significant decrease in P100 amplitude among regular cannabis users in low spatial frequency (F(1,67) = 4.43; p = 0.04) and in dynamic condition (F(1,67) = 4.35; p = 0.04). Analysis also reported a decrease in P100 area under the curve in regular cannabis users to low spatial frequency (F(1,67) = 4.31; p = 0.04) and in dynamic condition (F(1,67) = 7.65; p < 0.01). No effect was found on P100 latency, N170 amplitude, latency, or area under the curve. We found alteration of P100 responses to low spatial frequency and dynamic stimuli in regular cannabis users. This result could be interpreted as a preferential magnocellular impairment where such deficit could be linked to glutamatergic dysfunction. As mentioned in the literature, visual and electrophysiological anomalies in schizophrenia are related to a magnocellular dysfunction. Further studies are needed to clarify electrophysiological deficits in both populations. CLINICAL TRIALS REGISTRATION: Electrophysiological Study of the Functioning of Magnocellular Visual Pathway in Regular Cannabis Users (CAUSA MAP). [NCT02864680; ID 2013-A00097-38]. https://clinicaltrials.gov/ct2/show/NCT02864680?cond=Cannabis&cntry=FR&draw=2&rank=1.

Visual Dysfunction after Repetitive Mild Traumatic Brain Injury in a Mouse Model and Ramifications on Behavioral Metrics.

Mild traumatic brain injury (mTBI) is a major cause of morbidity and mortality with a poorly understood pathophysiology. Animal models have been increasingly utilized to better understand mTBI and recent research has identified visual deficits in these models that correspond to human literature. While visual impairment is being further characterized within TBI, the implications of impaired vision on behavioral tasks commonly utilized in animal models has not been well described thus far. Visual deficits may well confound behavioral tests that are believed to be isolated to cognitive functioning such as learning and memory. We utilized a mouse model of repetitive mTBI (rmTBI) to further characterize visual deficits using an optomotor task, electroretinogram, and visually evoked potential, and located likely areas of damage to the visual pathway. Mice were tested on multiple behavioral metrics, including a touchscreen conditional learning task to better identify the contribution of visual dysfunction to behavioral alterations. We found that rmTBI caused visual dysfunction resulting from damage distal to the retina that likely involves pathology within the optic nerve. Moreover, loss of vision led to poorer performance of rmTBI animals on classic behavioral tests such as the Morris water maze that would otherwise be attributed solely to learning and memory deficits. The touchscreen conditional learning task was able to differentiate rmTBI induced learning and memory dysfunction from visual impairment and is a valuable tool for elucidating subtle changes resulting from TBI.

High-Density EEG in a Charles Bonnet Syndrome Patient during and without Visual Hallucinations: A Case-Report Study.

Charles Bonnet syndrome (CBS) is a rare clinical condition characterized by complex visual hallucinations in people with loss of vision. So far, the neurobiological mechanisms underlying the hallucinations remain elusive. This case-report study aims at investigating electrical activity changes in a CBS patient during visual hallucinations, as compared to a resting-state period (without hallucinations). Prior to the EEG, the patient underwent neuropsychological, ophthalmologic, and neurological examinations. Spectral and connectivity, graph analyses and signal diversity were applied to high-density EEG data. Visual hallucinations (as compared to resting-state) were characterized by a significant reduction of power in the frontal areas, paralleled by an increase in the midline posterior regions in delta and theta bands and by an increase of alpha power in the occipital and midline posterior regions. We next observed a reduction of theta connectivity in the frontal and right posterior areas, which at a network level was complemented by a disruption of small-worldness (lower local and global efficiency) and by an increase of network modularity. Finally, we found a higher signal complexity especially when considering the frontal areas in the alpha band. The emergence of hallucinations may stem from these changes in the visual cortex and in core cortical regions encompassing both the default mode and the fronto-parietal attentional networks.

Cerebral visual impairment in CDKL5 deficiency disorder: vision as an outcome measure.

AIM: To characterize the neuro-ophthalmological phenotype of cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) and assess visual acuity as a reproducible, quantitative outcome measure. METHOD: We retrospectively analyzed clinical data from patients with CDD. Complete neuro-ophthalmological assessments, including visual acuity, were evaluated. RESULTS: Of 26 patients (22 females, four males; median age 4y, interquartile range 2y 1mo-7y 10mo), cerebral visual impairment (CVI), defined as visual dysfunction in the absence of ocular or anterior visual pathway abnormalities, was diagnosed in all those over 2 years of age. Ophthalmological examinations revealed nystagmus in 10 patients and strabismus in 24 patients. Visual acuity was measured in 24 patients, by preferential looking in all and by sweep visual evoked potential in 13. Visual acuities were lower than age expectations and demonstrated improvement in the first 3 years. Adjusting for age and sex, average preferential looking visual acuity after 2 years of age was higher in patients with intact mobility than in those who were non-mobile. INTERPRETATION: CVI was observed in patients with CDD. Visual acuity improved over time and correlated with mobility. Visual acuity, as a quantifiable measure of visual function, should be considered as an outcome measure in pre-clinical and clinical studies for CDD. What this paper adds Cerebral visual impairment is highly prevalent in cyclin-dependent kinase-like 5 deficiency disorder (CDD). Visual acuity is a measurable quantitative outcome measure in CDD. Visual acuity in CDD correlates with gross motor ability.

Intraoperative subcortico-cortical evoked potentials of the visual pathway under general anesthesia.

OBJECTIVE: To assess whether intraoperative subcortical mapping of the visual pathways during brain surgeries was feasible. METHODS: Subcortico-cortical evoked potentials (SCEPs: 30 stimulations/site, biphasic single pulse, 1.3 Hz, 0.2 ms/phase, maximum 10 mA; bipolar probe) were measured in 12 patients for stimulation of the optic radiation, Meyer's loop or optic nerve. Recorded sites were bilateral central, parietal, parieto-occipital, occipital (subdermal scalp electrodes, 5-4000 Hz). The minimum distances from the stimulation locations, i.e. the closest border of the resection cavity to the diffusion tensor imaging based visual pathways, were evaluated postoperatively (smallest distance across coronal, sagittal and axial planes). RESULTS: Stimulation elicited SCEPs when the visual tracts were close (≤4.5 mm). The responses consisted of a short (P1, 3.0-5.6 ms; 8/8 patients) and of a middle (P2, 15-21.6 ms; 3/8 patients) latency waveforms. In agreement with the neuroanatomy, ipsilateral occipital responses were obtained for temporal or parietal stimulations, and bi-occipital responses for optic nerve stimulations. CONCLUSIONS: For the first time to our knowledge, intraoperative SCEPs were observed for stimulations of the optic radiation and of Meyer's loop. Short latency responses were found in agreement with fast conduction of the visual pathway's connecting myelinated fibers. SIGNIFICANCE: The mapping of the visual pathways was found feasible for neurosurgeries under general anesthesia.

Dynamic functional connectivity changes in Parkinson's disease patients with REM sleep behavior disorder.

BACKGROUND: Rapid eye movement (REM) sleep behavior disorder (RBD) is one of the common nonmotor symptoms of Parkinson's disease (PD), characterized by frequently occurring REM sleep without muscle atonia. Our aim was to explore dynamic network connection changes in PD patients with RBD. METHOD: On the basis of RBD screening questionnaire (RBDSQ), 126 PD patients were classified into those with probable RBD symptoms (PD-pRBD) and without probable RBD (PD-npRBD). We applied independent component analysis, sliding window approach and k-means clustering methods to clarify dynamic functional connectivity alterations. RESULTS: In contrast to PD-npRBD, PD-pRBD patients were liable to engage in a brain pattern mainly marked by weaker positive couplings between visual network (VIS) and default mode network (DMN), DMN and basal ganglia network (BG), and within DMN (State IV). In addition, we discovered that both PD patients with or without pRBD had shorter dwell time and fewer occurrences in State III, characterized by positive correlations between VIS and DMN, BG and DMN, and positive within-network coupling of sensorimotor network (SMN), relative to healthy controls. CONCLUSIONS: Our study suggested that the weaker positive couplings between VIS and DMN, DMN and BG, and within DMN in State IV could be involved in the pathogenesis of PD patients with probable RBD on an overall level.

Visual Dysfunction in Multiple Sclerosis and its Animal Model, Experimental Autoimmune Encephalomyelitis: a Review.

Visual disabilities in central nervous system autoimmune diseases such as multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), are important symptoms. Past studies have focused on neuro-inflammatory changes and demyelination in the white matter of the brain and spinal cord. In MS, neuro-inflammatory lesions have been diagnosed in the visual pathway; the lesions may perturb visual function. Similarly, neuropathological changes in the retina and optic nerves have been found in animals with chronic EAE. Although the retina and optic nerves are immunologically privileged sites via the blood-retina barrier and blood-brain barrier, respectively, inflammation can occur via other routes, such as the uvea (e.g., iris and choroid) and cerebrospinal fluid in the meninges. This review primarily addresses the direct involvement of the blood-retina barrier and the blood-brain barrier in the development of retinitis and optic neuritis in EAE models. Additional routes, including pro-inflammatory mediator-filled choroidal and subarachnoid spaces, are also discussed with respect to their roles in EAE-induced visual disability and as analogues of MS in humans.

Abnormal intrinsic functional network hubs in diabetic retinopathy patients.

BACKGROUND: However, whether the whole-brain functional network hub changes occur in diabetic retinopathy patients remains unknown. PURPOSE: The purpose of the study was to investigate the function network centrality and connectivity changes in diabetic retinopathy patients using the voxel-wise degree centrality method. MATERIALS AND METHODS: Thirty-four diabetic retinopathy patients (18 male and 16 female) and 38 healthy controls (18 male and 20 female) closely matched in age, sex, and education were enrolled in the study. Graph theory-based network analysis was performed to investigate the degree centrality between two groups. RESULTS: Compared with healthy controls, diabetic retinopathy patients had significantly higher degree centrality values in the pons and bilateral caudate and had significantly lower degree centrality values in the left lingual and right lingual, and right angular/middle occipital gyrus (MOG). Moreover, diabetic retinopathy patients exhibited increased functional connectivity between the bilateral lingual and right cerebellum lobe and right fusiform/bilateral caudate and increased functional connectivity between the right angular/MOG and bilateral anterior cingulum and right cuneus/bilateral precuneus and increased functional connectivity between the bilateral caudate and right lingual and right superior occipital gyrus. In contrast, diabetic retinopathy patients showed decreased functional connectivity between bilateral lingual and left lingual and right lingual and left superior occipital gyrus and decreased functional connectivity between the angular/MOG and right inferior occipital gyrus/right fusiform and left MOG/inferior occipital gyrus and decreased functional connectivity between the bilateral caudate and bilateral cerebellum crus1. CONCLUSION: Our results highlight that reorganization of the hierarchy of the cortical connectivity network related to visual network.

The Role of the Thalamus in Post-Traumatic Stress Disorder.

Post-traumatic stress disorder (PTSD) has a high lifetime prevalence and is one of the more serious challenges in mental health care. Fear-conditioned learning involving the amygdala has been thought to be one of the main causative factors; however, recent studies have reported abnormalities in the thalamus of PTSD patients, which may explain the mechanism of interventions such as eye movement desensitization and reprocessing (EMDR). Therefore, I conducted a miniature literature review on the potential contribution of the thalamus to the pathogenesis of PTSD and the validation of therapeutic approaches. As a result, we noticed the importance of the retinotectal pathway (superior colliculus-pulvinar-amygdala connection) and discussed therapeutic indicators.

Quantitative assessment of visual pathway function in blind retinitis pigmentosa patients.

OBJECTIVE: The current methods used to assess visual function in blind retinitis pigmentosa (RP) patients are mostly subjective. We aimed to identify effective, objective methods. METHODS: We enrolled patients diagnosed with blindness associated with RP; we finally selected 26 patients (51 eyes) with a visual field radius less than 10 degrees and divided them into the following 4 groups by best-corrected visual acuity (BCVA): group 1, no light perception (NLP, 4 eyes); group 2, light perception (LP, 12 eyes); group 3, hand movement or finger counting (faint form perception, FFP, 22 eyes); and group 4, BCVA from 0.1 to 0.8 (form perception, FP, 13 eyes). All patients underwent optometry, optical coherence tomography (OCT), color fundus photography, fundus autofluorescence (FAF), full field electroretinography (ffERG), pattern electroretinography (PERG), multifocal electroretinography (mf-ERG), pattern visual evoked potential (PVEP), flash visual evoked potential (FVEP), and pupillary light response (PLR) assessments. Five patients in groups 1, 2, and 3 (1, 2, and 2 subjects, respectively) underwent functional magnetic resonance imaging (fMRI) scans and were compared with five healthy subjects. RESULTS: The outer plexiform layer was thinner in group 1, and the outer nuclear layer was thinner in groups 1 and 2. The ffERG, PERG, and mf-ERG findings were unrecordable in all four groups. The P2 amplitude of the FVEP was significantly lower in groups 1 and 2, while the P100 amplitude of the PVEP was higher in groups 2, 3 and 4 than in group 1. After white- and blue-light stimuli, the PLR thresholds in the patients without form perception were significantly higher. The threshold of the PLR stimulated by blue and white light was negatively correlated with the amplitudes of P2 and P100. Moreover, the fMRI findings showed that some RP patients have significant visual cortex activation in response to certain types of stimulation. However, statistical analysis was not performed because of the small number of cases. CONCLUSIONS: OCT, VEP, PLR and fMRI assessments can evaluate residual visual pathway function in blind RP patients. SIGNIFICANCE: Our study may have clinical significance for the potential prediction of RP patient prognoses and the effects after clinical trials.

Evaluation of the patients diagnosed as idiopathic intracranial hypertension with and without papilledema visual pathways by analysis of visual evoked potential.

Background Idiopathic intracranial hypertension (IIH) is a clinical syndrome characterized by increased intracranial pressure in the absence of clinical, laboratory, or radiological findings of space-occupying lesion in the cranium. Papilledema is found in majority of the patients with IIH while it is absent in only about 5-6% of the patients. Methods Our primary objective was to evaluate the patients with IIH with (n: 45) and without (n: 15) papilledema using cranial MRI and VEP analyses and to compare the obtained results. Diagnosis of IIH according to ICHD-3 criteria admitted to and followed in our clinic before receiving any treatment between 2008 and 2018 were reviewed retrospectively after obtaining approval from the Ethics Committee. Results There was no statistically significant difference between both groups' ages (P: 0.494) while differences in lumbar puncture (LP) opening pressure and VAS were found to be statistically significant (p = 0.034, 0.001, respectively). In our VEP investigation, it was seen that latencies in the group without papilledema were seen to be closer to those in the control group (P latency: 0.706, P amplitude: 0.080). Increase in latency and decrease in amplitude were seen in the group with papilledema compared to the group without papilledema (p < 0.001). Conclusion In conclusion, alterations in the optic nerve may be detected with VEP investigation before the detection of papilledema through ophthalmoscopic examination in these patients. Thus, VEP investigation may be considered to have predictive value. VEP examination may be recommended in diagnosis and treatment and during follow-up periods.

Highlights Clinical imaging (cranial MRI-MR-angiography-venography) and VEP analyses were evaluated comparatively with detail in the patients with and without papilledema. In the literature, there are studies on VEP analysis. They have been done on acute and chronic stages of idiopathic intracranial hypertension. In the present study, the patients with and without papilledema were compared in contrast to other studies. Increased VEP latency was seen in both groups being especially more prominent in the group with papilledema.

Dysfunction in macula, retinal pigment epithelium and post retinal pathway in acute organophosphorus poisoning.

CONTEXT: Organophosphorus (OP) insecticide poisoning is a significant health problem in South Asian countries. Although cholinergic receptors are present at the junction between photoreceptors and the retinal pigment epithelium (RPE), human studies of the effects of OP poisoning on the visual pathways are very few. This study aims to demonstrate the pattern of changes in retina and post retinal pathways in patients with acute OP poisoning using visual electrophysiological tests. METHODS: This is an observational, cross-sectional study conducted at the Neurophysiology Unit, Teaching Hospital, Peradeniya, Sri Lanka. We tested 16 patients recovered from cholinergic phase, at least 24 h after deatropinization and within 8 weeks of OP ingestion. We assessed the functional integrity of the photoreceptors and ganglion cells of the macula by pattern electroretinography (PERG); RPE by electro-oculography (EOG); and post retinal pathways by pattern reversal visual evoked potentials (PR-VEP). Latencies and amplitudes of PR-VEP and PERG, light peak (LP), dark trough (DT) and Arden ratio of EOG were determined in patients and compared with 16 controls using the Mann-Whitney U test. RESULTS: Of the 16 OP-poisoned patients (median age of 37 ± IQR 20 years), six (37.5%) had reduced Arden ratio with reference to the International Society of Clinical Electrophysiology of Vision cut-off value of 1.7. The median Arden ratio in patients (1.69 ± IQR 0.36) was significantly lower compared to controls (1.90 ± IQR 0.4). The median latencies and amplitudes of PR-VEP or PERG were not significantly different between patients and controls. However, three patients had prolonged P100 latencies in PR-VEP and one had prolonged P50 latency in PERG. CONCLUSIONS: Acute OP poisoning seems to affect the functions of the RPE and the visual electrophysiological changes outlast the cholinergic phase. Limited evidence suggests that photoreceptors of the macula region and post retinal pathway might be affected in some patients.

V1 Projection Zone Signals in Human Macular Degeneration Depend on Task Despite Absence of Visual Stimulus.

Identifying the plastic and stable components of the visual cortex after retinal loss is an important topic in visual neuroscience and neuro-ophthalmology.1-5 Humans with juvenile macular degeneration (JMD) show significant blood-oxygen-level-dependent (BOLD) responses in the primary visual area (V1) lesion projection zone (LPZ),6 despite the absence of the feedforward signals from the degenerated retina. Our previous study7 reported that V1 LPZ responds to full-field visual stimuli during the one-back task (OBT), not during passive viewing, suggesting the involvement of task-related feedback signals. Aiming to clarify whether visual inputs to the intact retina are necessary for the LPZ responses, here, we measured BOLD responses to tactile and auditory stimuli for both JMD patients and control participants with and without OBT. Participants were instructed to close their eyes during the experiment for the purpose of eliminating retinal inputs. Without OBT, no V1 responses were detected in both groups of participants. With OBT, to the contrary, both stimuli caused substantial V1 responses in JMD patients, but not controls. Furthermore, we also found that the task-dependent activity in V1 LPZ became less pronounced when JMD patients opened their eyes, suggesting that task-related feedback signals can be partially suppressed by residual feedforward signals. Modality-independent V1 LPZ responses only in the task condition suggest that V1 LPZ responses reflect task-related feedback signals rather than reorganized feedforward visual inputs.

Data-Driven Classification of Spectral Profiles Reveals Brain Region-Specific Plasticity in Blindness.

Congenital blindness has been shown to result in behavioral adaptation and neuronal reorganization, but the underlying neuronal mechanisms are largely unknown. Brain rhythms are characteristic for anatomically defined brain regions and provide a putative mechanistic link to cognitive processes. In a novel approach, using magnetoencephalography resting state data of congenitally blind and sighted humans, deprivation-related changes in spectral profiles were mapped to the cortex using clustering and classification procedures. Altered spectral profiles in visual areas suggest changes in visual alpha-gamma band inhibitory-excitatory circuits. Remarkably, spectral profiles were also altered in auditory and right frontal areas showing increased power in theta-to-beta frequency bands in blind compared with sighted individuals, possibly related to adaptive auditory and higher cognitive processing. Moreover, occipital alpha correlated with microstructural white matter properties extending bilaterally across posterior parts of the brain. We provide evidence that visual deprivation selectively modulates spectral profiles, possibly reflecting structural and functional adaptation.

Dynamic brain fluctuations outperform connectivity measures and mirror pathophysiological profiles across dementia subtypes: A multicenter study.

From molecular mechanisms to global brain networks, atypical fluctuations are the hallmark of neurodegeneration. Yet, traditional fMRI research on resting-state networks (RSNs) has favored static and average connectivity methods, which by overlooking the fluctuation dynamics triggered by neurodegeneration, have yielded inconsistent results. The present multicenter study introduces a data-driven machine learning pipeline based on dynamic connectivity fluctuation analysis (DCFA) on RS-fMRI data from 300 participants belonging to three groups: behavioral variant frontotemporal dementia (bvFTD) patients, Alzheimer's disease (AD) patients, and healthy controls. We considered non-linear oscillatory patterns across combined and individual resting-state networks (RSNs), namely: the salience network (SN), mostly affected in bvFTD; the default mode network (DMN), mostly affected in AD; the executive network (EN), partially compromised in both conditions; the motor network (MN); and the visual network (VN). These RSNs were entered as features for dementia classification using a recent robust machine learning approach (a Bayesian hyperparameter tuned Gradient Boosting Machines (GBM) algorithm), across four independent datasets with different MR scanners and recording parameters. The machine learning classification accuracy analysis revealed a systematic and unique tailored architecture of RSN disruption. The classification accuracy ranking showed that the most affected networks for bvFTD were the SN + EN network pair (mean accuracy = 86.43%, AUC = 0.91, sensitivity = 86.45%, specificity = 87.54%); for AD, the DMN + EN network pair (mean accuracy = 86.63%, AUC = 0.89, sensitivity = 88.37%, specificity = 84.62%); and for the bvFTD vs. AD classification, the DMN + SN network pair (mean accuracy = 82.67%, AUC = 0.86, sensitivity = 81.27%, specificity = 83.01%). Moreover, the DFCA classification systematically outperformed canonical connectivity approaches (including both static and linear dynamic connectivity). Our findings suggest that non-linear dynamical fluctuations surpass two traditional seed-based functional connectivity approaches and provide a pathophysiological characterization of global brain networks in neurodegenerative conditions (AD and bvFTD) across multicenter data.

Characterizing Inscapes and resting-state in MEG: Effects in typical and atypical development.

Examining the brain at rest is a powerful approach used to understand the intrinsic properties of typical and disordered human brain function, yet task-free paradigms are associated with greater head motion, particularly in young and/or clinical populations such as autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD). Inscapes, a non-social and non-verbal movie paradigm, has been introduced to increase attention, thus mitigating head motion, while reducing the task-induced activations found during typical movie watching. Inscapes has not yet been validated for use in magnetoencephalography (MEG), and it has yet to be shown whether its effects are stable in clinical populations. Across typically developing (N = 32) children and adolescents and those with ASD (N = 46) and ADHD (N = 42), we demonstrate that head motion is reduced during Inscapes. Due to the task state evoked by movie paradigms, we also expectedly observed concomitant modulations in local neural activity (oscillatory power) and functional connectivity (phase and envelope coupling) in intrinsic resting-state networks and across the frequency spectra compared to a fixation cross resting-state. Increases in local activity were accompanied by decreases in low-frequency connectivity within and between resting-state networks, primarily the visual network, suggesting that task-state evoked by Inscapes moderates ongoing and spontaneous cortical inhibition that forms the idling intrinsic networks found during a fixation cross resting-state. Importantly, these effects were similar in ASD and ADHD, making Inscapes a well-suited advancement for investigations of resting brain function in young and clinical populations.

In Vivo Evidence for Impaired Glymphatic Function in the Visual Pathway of Patients With Normal Pressure Hydrocephalus.

Purpose: Impaired ability to remove toxic metabolites from central nervous system may be an important link between cerebral and ophthalmic degenerative diseases. The aim of the present study was to compare the glymphatic function in the visual pathway in patients with idiopathic normal pressure hydrocephalus (iNPH), a neurodegenerative dementia subtype, with a reference group. Methods: We compared 31 subjects with Definite iNPH (i.e., shunt-responsive) with 13 references in a prospective and observational study. After intrathecal injection of the magnetic contrast agent gadobutrol (Gadovist, 0.5 mL, 1.0 mmol/mL, Bayer Pharma AG), serving as a tracer, consecutive magnetic resonance imaging (MRI) scans were obtained (next 24-48 hours). The normalized MRI T1 signal recorded in the cerebrospinal fluid (CSF) and along the visual pathway served as a semi-quantitative measure of tracer enrichment. Gadobutrol does not penetrate the blood-brain barrier and is thus confined to the extravascular space. Overnight measurements of pulsatile intracranial pressure were used as a surrogate marker for the intracranial compliance. Results: The tracer enriched the prechiasmatic cistern similarly in both groups, but clearance was delayed in the iNPH group. Moreover, both delayed enrichment and clearance of the tracer were observed in the visual pathway in the iNPH subjects. The enrichment in the visual pathway and the CSF correlated. Individuals with elevated pulsatile intracranial pressure showed reduced enrichment within the visual pathway. Conclusions: There was delayed enrichment and clearance of a tracer in the visual pathway of iNPH patients, which suggests impaired glymphatic function in the visual pathway in this disease.

The Dynamics of Functional Brain Networks Associated With Depressive Symptoms in a Nonclinical Sample.

Brain function depends on the flexible and dynamic coordination of functional subsystems within distributed neural networks operating on multiple scales. Recent progress has been made in the characterization of functional connectivity (FC) at the whole-brain scale from a dynamic, rather than static, perspective, but its validity for cognitive sciences remains under debate. Here, we analyzed brain activity recorded with functional Magnetic Resonance Imaging from 71 healthy participants evaluated for depressive symptoms after a relationship breakup based on the conventional Major Depression Inventory (MDI). We compared both static and dynamic FC patterns between participants reporting high and low depressive symptoms. Between-group differences in static FC were estimated using a standard pipeline for network-based statistic (NBS). Additionally, FC was analyzed from a dynamic perspective by characterizing the occupancy, lifetime, and transition profiles of recurrent FC patterns. Recurrent FC patterns were defined by clustering the BOLD phase-locking patterns obtained using leading eigenvector dynamics analysis (LEiDA). NBS analysis revealed a brain subsystem exhibiting significantly lower within-subsystem correlation values in more depressed participants (high MDI). This subsystem predominantly comprised connections between regions of the default mode network (i.e., precuneus) and regions outside this network. On the other hand, LEiDA results showed that high MDI participants engaged more in a state connecting regions of the default mode, memory retrieval, and frontoparietal network (p-FDR = 0.012); and less in a state connecting mostly the visual and dorsal attention systems (p-FDR = 0.004). Although both our analyses on static and dynamic FC implicate the role of the precuneus in depressive symptoms, only including the temporal evolution of BOLD FC helped to disentangle over time the distinct configurations in which this region plays a role. This finding further indicates that a holistic understanding of brain function can only be gleaned if the temporal dynamics of FC is included.