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Brain atrophy and cortical thinning are typically observed in people with Alzheimer's disease (AD) and, to a lesser extent, in those with mild cognitive impairment. In asymptomatic middle-aged apolipoprotein ε4 (ΑPOE4) carriers, who are at higher risk of future AD, study reports are discordant with limited evidence of brain structural differences between carriers and non-carriers of the ε4 allele. Alternative imaging markers with higher sensitivity at the presymptomatic stage, ideally quantified using typically acquired structural MRI scans, would thus be of great benefit for the detection of early disease, disease monitoring and subject stratification. In the present cross-sectional study, we investigated textural properties of T1-weighted 3T MRI scans in relation to APOE4 genotype, age and sex. We pooled together data from the PREVENT-Dementia and ALFA studies focused on midlife healthy populations with dementia risk factors (analysable cohort: 1585 participants; mean age 56.2 ± 7.4 years). Voxel-based and texture (examined features: contrast, entropy, energy, homogeneity) based morphometry was used to identify areas of volumetric and textural differences between APOE4 carriers and non-carriers. Textural maps were generated and were subsequently harmonised using voxel-wise COMBAT. For all analyses, APOE4, sex, age and years of education were used as model predictors. Interactions between APOE4 and age were further examined. There were no group differences in regional brain volume or texture based on APOE4 carriership or when age × APOE4 interactions were examined. Older people tended to have a less homogeneous textural profile in grey and white matter and a more homogeneous profile in the ventricles. A more heterogeneous textural profile was observed for females in areas such as the ventricles, frontal and parietal lobes and for males in the brainstem, cerebellum, precuneus and cingulate. Overall, we have shown the absence of volumetric and textural differences between APOE4 carriers and non-carriers at midlife and have established associations of textural features with ageing and sex., (© 2024 The Author(s). Human Brain Mapping published by Wiley Periodicals LLC.)

Most people have a soundtrack of life, a set of special musical pieces closely linked to certain biographical experiences. Autobiographical memories (AM) and music listening (ML) involve complex mental processes ruled by differentiate brain networks. The aim of the paper was to determine the way both networks interact in linked occurrences. We performed an fMRI experiment on 31 healthy participants (age: 32.4 ± 7.6, 11 men, 4 left-handers). Participants had to recall AMs prompted by music they reported to be associated with personal biographical events (LMM: linked AM-ML events). In the main control task, participants were prompted to recall emotional AMs while listening known tracks from a pool of popular music (UMM: unlinked AM-ML events). We wanted to investigate to what extent LMM network exceeded the overlap of AM and ML networks by contrasting the activation obtained in LMM versus UMM. The contrast LMM>UMM showed the areas (at P < 0.05 FWE corrected at voxel level and cluster size>20): right frontal inferior operculum, frontal middle gyrus, pars triangularis of inferior frontal gyrus, occipital superior gyrus and bilateral basal ganglia (caudate, putamen and pallidum), occipital (middle and inferior), parietal (inferior and superior), precentral and cerebellum (6, 7 L, 8 and vermis 6 and 7). Complementary results were obtained from additional control tasks. Provided part of tLMM>UMM areas might not be related to ML-AM linkage, we assessed LMM brain network by an independent component analysis (ICA) on contrast images. Results from ICA suggest the existence of a cortico-ponto-cerebellar network including left precuneus, bilateral anterior cingulum, parahippocampal gyri, frontal inferior operculum, ventral anterior part of the insula, frontal medial orbital gyri, caudate nuclei, cerebellum 6 and vermis, which might rule the ML-induced retrieval of AM in closely linked AM-ML events. This topography may suggest that the pathway by which ML is linked to AM is attentional and directly related to perceptual processing, involving salience network, instead of the natural way of remembering typically associated with default mode network., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Among others, the existence of pathophysiological biomarkers such as cerebrospinal fluid (CSF) Aβ-42, t-tau, and p-tau preceding the onset of Alzheimer's disease (AD) symptomatology have shifted the conceptualization of AD as a continuum. In addition, magnetic resonance imaging (MRI) enables the study of structural and functional cross-sectional correlates and longitudinal changes in vivo and, therefore, the combination of CSF data and imaging analyses emerges as a synergistic approach to understand the structural correlates related with specific AD-related biomarkers. In this chapter, we describe the methods used in neuroimaging that will allow researchers to combine data on CSF metabolites with imaging analyses.

The identification of healthy individuals harboring amyloid pathology represents one important challenge for secondary prevention clinical trials in Alzheimer's disease (AD). Consequently, noninvasive and cost-efficient techniques to detect preclinical AD constitute an unmet need of critical importance. In this manuscript, we apply machine learning to structural MRI (T1 and DTI) of 96 cognitively normal subjects to identify amyloid-positive ones. Models were trained on public ADNI data and validated on an independent local cohort. Used for subject classification in a simulated clinical trial setting, the proposed method is able to save 60% of unnecessary CSF/PET tests and to reduce 47% of the cost of recruitment. This recruitment strategy capitalizes on available MR scans to reduce the overall amount of invasive PET/CSF tests in prevention trials, demonstrating a potential value as a tool for preclinical AD screening. This protocol could foster the development of secondary prevention strategies for AD.

Aim: To evaluate the potential reorganization of the sensorimotor cortex in a patient with traumatic brain injury after an intensive motor rehabilitation., Patients and Methods: A 17-year-old male with severe traumatic brain injury was submitted to functional magnetic resonance imaging (fMRI) analyses of motor control before and after motor rehabilitation. The motor tasks performed during fMRI were finger tapping, ankle plantar flexion, and toe flexion., Results: Prior to treatment, the cerebrally activated areas for the right hand during finger tapping were the primary motor (M1), supplementary motor area (SMA), superior parietal and postcentral areas. For the left hand, the areas were the M1 and the cerebellum. After treatment, the activated areas were the pre and postcentral areas for the right hand and the precentral area for the left hand. For the foot motor-task, the activated areas prior to treatment were the paracentral area for the right foot, and the SMA, paracentral and poscentral areas for the left. After treatment, activation for the right foot was seen in the paracentral area, and activation for the left foot was seen in the paracentral area and SMA., Conclusions: The decrease in the post-treatment activation pattern could be explained as a cortical reorganization, which in the current study was related to motor skill and motor automatism acquired by the patient.

Objective: To investigate whether preterm children with low risk for neurodevelopmental deficits show long-term changes in gray matter (GM) and white matter (WM) volumes compared with term children and to relate these changes to cognitive outcome., Methods: MRI was used to evaluate 20 preterm children who were determined to be at low risk for neurodevelopmental deficits and were born between 30 and 34 weeks' gestational age without major neonatal morbidity or cerebral pathology in the neonatal period and 22 matched, term control subjects. Volumetric images were analyzed by means of voxel-based morphometry to identify regional cerebral alterations. Children also underwent cognitive and behavioral/emotional assessments., Results: Preterm children showed global and regional GM volume reductions in several brain areas, including temporal and parietal lobes and concomitant WM volume reductions in the same areas, although only the left temporal regions achieved statistical significance. Global intellectual performance in the preterm group was significantly decreased compared with control subjects. Neither behavioral nor emotional problems were found in the preterm group. In the whole sample, we found a positive correlation between GM volume bilaterally in the middle temporal and in the postcentral gyri with IQ. Positive correlations were observed between GM and gestational age at birth in parietal and temporal cerebral regions and with WM in parietal regions., Conclusion: Preterm birth has an important impact on the neurodevelopmental and cognitive outcome of children at 9 years of age, being a risk factor for decreased regional cortical GM and WM even in preterm children with low risk for neurodevelopmental deficits.

The objective was to examine whether cerebral volumes are reduced, and in what regions, in adolescents with anorexia nervosa and to study changes after nutritional recovery. Twelve anorexia nervosa (DSM-IV) patients aged 11-17 consecutively admitted to an Eating Disorders Unit were assessed by means of psychopathological scales, neuropsychological battery and voxel-based morphometric (VBM) magnetic resonance imaging at admission and after 7 months' follow-up. Nine control subjects of similar age, gender and estimated intelligence level were also studied. The two groups showed differences in gray matter (F=22.2; p<0.001) and cerebrospinal fluid (CSF) (F=21.2; p<0.001) but not in white matter volumes. In anorexic patients, gray matter volume correlated negatively with the copy time from the Rey Complex Figure Test. In the regional VBM study several temporal and parietal gray matter regions were reduced. During follow-up there was a greater global increase in gray matter (F=10.7; p=0.004) and decrease in CSF (F=22.1; p=0.001) in anorexic patients. The increase in gray matter correlated with a decrease in cortisol (Spearman correlation=-0.73; p=0.017). At follow-up there were no differences in global gray matter (F=2.1; p=0.165), white matter (F=0.02, p=0.965) or CSF (F=1.8; p=0.113) volumes between both groups. There were still some smaller areas, in the right temporal and both supplementary motor area, showing differences between them in the regional VBM study. In conclusion, in adolescent anorexic patients gray matter is more affected than white matter and mainly involves the posterior regions of the brain. Overall gray matter alterations are reversible after nutritional recovery.

Traumatic brain injury (TBI) patients have working memory deficits and altered patterns of brain activation during this function. The evolution of the impairment has not been examined to date. This study investigated longitudinal changes in brain activation during a working memory task. Twelve patients with severe and diffuse TBI and ten healthy matched controls were fMRI scanned twice at a 6-month interval during an n-back task (0-, 2- and 3-back). All the TBI patients selected presented signs of diffuse axonal injury on CT but had no evidence of focal lesions on MRI clinical examination. Significant changes in brain activation over time were observed in patients, but not in controls. During the first examination, though both groups engaged bilateral fronto-parietal regions known to be involved in working memory, activation of the right superior frontal gyrus was low in the TBI group. However, the difference between TBI and controls had decreased significantly after 6 months. A factor analysis confirmed the greater increase in activation in the right superior frontal cortex in the TBI group than in healthy controls, leading to normalization of the brain activation pattern. In conclusion, this longitudinal study provides evidence of a progressive normalization of the working memory activation pattern after diffuse axonal injury in severe TBI, coinciding with an improvement in performance on this function.

INTRODUCTION: Cerebral blood flow (CBF) is reduced in cognitively impaired (CI) Alzheimer's disease (AD) patients. We checked the sensitivity of time‐encoded arterial spin labeling (te‐ASL) in measuring CBF alterations in individuals with positive AD biomarkers and associations with relevant biomarkers in cognitively unimpaired (CU) individuals. METHODS: We compared te‐ASL with single‐postlabel delay (PLD) ASL in measuring CBF in 59 adults across the AD continuum, classified as CU amyloid beta (Aβ) negative (−), CU Aβ positive (+), and CI Aβ+. We sought associations of CBF with biomarkers of AD, cerebrovascular disease, synaptic dysfunction, neurodegeneration, and cognition in CU participants. RESULTS: te‐ASL was more sensitive at detecting CBF reduction in the CU Aβ+ and CI Aβ+ groups. In CU participants, lower CBF was associated with altered biomarkers of Aβ, tau, synaptic dysfunction, and neurodegeneration. DISCUSSION: CBF reduction occurs early in the AD continuum. te‐ASL is more sensitive than single‐PLD ASL at detecting CBF changes in AD. Highlights: Lower CBF can be detected in CU subjects in the early AD continuum.te‐ASL is more sensitive than single‐PLD ASL at detecting CBF alterations in AD.CBF is linked to biomarkers of AD, synaptic dysfunction, and neurodegeneration. [ABSTRACT FROM AUTHOR]

Objective: Along with the known effects of stress on brain structure and inflammatory processes, increasing evidence suggest a role of chronic stress in the pathogenesis of Alzheimer's disease (AD). We investigated the association of accumulated stressful life events (SLEs) with AD pathologies, neuroinflammation, and gray matter (GM) volume among cognitively unimpaired (CU) individuals at heightened risk of AD. Methods: This cross‐sectional cohort study included 1,290 CU participants (aged 48–77) from the ALFA cohort with SLE, lumbar puncture (n = 393), and/or structural magnetic resonance imaging (n = 1,234) assessments. Using multiple regression analyses, we examined the associations of total SLEs with cerebrospinal fluid (1) phosphorylated (p)‐tau181 and Aβ1–42/1–40 ratio, (2) interleukin 6 (IL‐6), and (3) GM volumes voxel‐wise. Further, we performed stratified and interaction analyses with sex, history of psychiatric disease, and evaluated SLEs during specific life periods. Results: Within the whole sample, only childhood and midlife SLEs, but not total SLEs, were associated with AD pathophysiology and neuroinflammation. Among those with a history of psychiatric disease SLEs were associated with higher p‐tau181 and IL‐6. Participants with history of psychiatric disease and men, showed lower Aβ1–42/1–40 with higher SLEs. Participants with history of psychiatric disease and women showed reduced GM volumes in somatic regions and prefrontal and limbic regions, respectively. Interpretation: We did not find evidence supporting the association of total SLEs with AD, neuroinflammation, and atrophy pathways. Instead, the associations appear to be contingent on events occurring during early and midlife, sex and history of psychiatric disease. ANN NEUROL 2024;95:1058–1068 [ABSTRACT FROM AUTHOR]

Purpose: To determine whether the APOE-ε4 allele modulates the relationship between regional β-amyloid (Aβ) accumulation and cognitive change in middle-aged cognitively unimpaired (CU) participants. Methods: The 352 CU participants (mean aged 61.1 [4.7] years) included completed two cognitive assessments (average interval 3.34 years), underwent [18F]flutemetamol Aβ positron emission tomography (PET), T1w magnetic resonance imaging (MRI), as well as APOE genotyping. Global and regional Aβ PET positivity was assessed across five regions-of-interest by visual reading (VR) and regional Centiloids. Linear regression models were developed to examine the interaction between regional and global Aβ PET positivity and APOE-ε4 status on longitudinal cognitive change assessed with the Preclinical Alzheimer's Cognitive Composite (PACC), episodic memory, and executive function, after controlling for age, sex, education, cognitive baseline scores, and hippocampal volume. Results: In total, 57 participants (16.2%) were VR+ of whom 41 (71.9%) were APOE-ε4 carriers. No significant APOE-ε4*global Aβ PET interactions were associated with cognitive change for any cognitive test. However, APOE-ε4 carriers who were VR+ in temporal areas (n = 19 [9.81%], p = 0.04) and in the striatum (n = 8 [4.14%], p = 0.01) exhibited a higher decline in the PACC. The temporal areas findings were replicated when regional PET positivity was determined with Centiloid values. Regionally, VR+ in the striatum was associated with higher memory decline. As for executive function, interactions between APOE-ε4 and regional VR+ were found in temporal and parietal regions, and in the striatum. Conclusion: CU APOE-ε4 carriers with a positive Aβ PET VR in regions known to accumulate amyloid at later stages of the Alzheimer's disease (AD) continuum exhibited a steeper cognitive decline. This work supports the contention that regional VR of Aβ PET might convey prognostic information about future cognitive decline in individuals at higher risk of developing AD. ClinicalTrials.gov Identifier: NCT02485730. Registered 20 June 2015 https://clinicaltrials.gov/ct2/show/NCT02485730 and ClinicalTrials.gov Identifier:NCT02685969. Registered 19 February 2016 https://clinicaltrials.gov/ct2/show/NCT02685969. [ABSTRACT FROM AUTHOR]

White matter hyperintensities (WMH) are commonly detected in the brain of elderly individuals and have been associated with a negative impact on multiple cognitive domains. We aim to investigate the impact of global and regional distribution of WMH on episodic memory and executive function in middle-aged cognitively unimpaired participants [N = 561 (45–75 years)] enriched for Alzheimer's disease risk factors. WMH were automatically segmented from FLAIR, T1 and FSE MR images. WMH load was calculated both globally and regionally. At each cerebral lobe, regional WMH load was measured at four equidistant layers extending from the lateral ventricles to juxtacortical areas. Cognition was measured by The Memory Binding Test (MBT) and WAIS-IV subtests. Global composite z-scores were calculated for the two cognitive domains. Association between global and regional WMH measurements were sought against cognitive measures, both in global composite scores and in individual subtests. We adjusted cognition and WMH burden for the main sociodemographic (age, sex and education) and genetic factors (APOE-ε4). Memory and executive function were significantly associated with global WMH load. Regionally, lower executive performance was mainly associated with higher deep WMH load in frontal areas and, to a lower degree, in occipital, parietal and temporal regions. Lower episodic memory performance was correlated with higher WMH burden in deep frontal and occipital areas. Our novel methodological approach of regional analysis allowed us to reveal the association between cognition and WMH in strategic brain locations. Our results suggest that, even a small WMH load can impact cognition in cognitively unimpaired middle-aged subjects. [ABSTRACT FROM AUTHOR]

Research into hippocampal self-regulation abilities may help determine the clinical significance of hippocampal hyperactivity throughout the pathophysiological continuum of Alzheimer's disease. In this study, we aimed to identify the effects of amyloid-β peptide 42 (amyloid-β42) and phosphorylated tau on the patterns of functional connectomics involved in hippocampal downregulation. We identified 48 cognitively unimpaired participants (22 with elevated CSF amyloid-β peptide 42 levels, 15 with elevated CSF phosphorylated tau levels, mean age of 62.705 ± 4.628 years), from the population-based 'Alzheimer's and Families' study, with baseline MRI, CSF biomarkers, APOE genotyping and neuropsychological evaluation. We developed a closed-loop, real-time functional MRI neurofeedback task with virtual reality and tailored it for training downregulation of hippocampal subfield cornu ammonis 1 (CA1). Neurofeedback performance score, cognitive reserve score, hippocampal volume, number of apolipoprotein ε4 alleles and sex were controlled for as confounds in all cross-sectional analyses. First, using voxel-wise multiple regression analysis and controlling for CSF biomarkers, we identified the effect of healthy ageing on eigenvector centrality, a measure of each voxel's overall influence based on iterative whole-brain connectomics, during hippocampal CA1 downregulation. Then, controlling for age, we identified the effects of abnormal CSF amyloid-β42 and phosphorylated tau levels on eigenvector centrality during hippocampal CA1 downregulation. Across subjects, our main findings during hippocampal downregulation were: (i) in the absence of abnormal biomarkers, age correlated with eigenvector centrality negatively in the insula and midcingulate cortex, and positively in the inferior temporal gyrus; (ii) abnormal CSF amyloid-β42 (<1098) correlated negatively with eigenvector centrality in the anterior cingulate cortex and primary motor cortex; and (iii) abnormal CSF phosphorylated tau levels (>19.2) correlated with eigenvector centrality positively in the ventral striatum, anterior cingulate and somatosensory cortex, and negatively in the precuneus and orbitofrontal cortex. During resting state functional MRI, similar eigenvector centrality patterns in the cingulate had previously been associated to CSF biomarkers in mild cognitive impairment and dementia patients. Using the developed closed-loop paradigm, we observed such patterns, which are characteristic of advanced disease stages, during a much earlier presymptomatic phase. In the absence of CSF biomarkers, our non-invasive, interactive, adaptive and gamified neuroimaging procedure may provide important information for clinical prognosis and monitoring of therapeutic efficacy. We have released the developed paradigm and analysis pipeline as open-source software to facilitate replication studies. [ABSTRACT FROM AUTHOR]

Cerebral white matter hyperintensities are believed the consequence of small vessel disease and are associated with risk and progression of Alzheimer's disease. The ɛ4 allele of the APOE gene is the major factor accountable for Alzheimer's disease heritability. However, the relationship between white matter hyperintensities and APOE genotype in healthy subjects remains controversial. We investigated the association between APOE-ɛ4 and vascular risk factors with white matter hyperintensities, and explored their interactions, in a cohort of cognitively healthy adults (45–75 years). White matter hyperintensities were assessed with the Fazekas Scale from magnetic resonance images (575 participants: 74 APOE-ɛ4 homozygotes, 220 heterozygotes and 281 noncarriers) and classified into normal (Fazekas < 2) and pathological (≥2). Stepwise logistic regression was used to study the association between pathological Fazekas and APOE genotype after correcting for cardiovascular and sociodemographic factors. APOE-ɛ4 homozygotes, but not heterozygotes, bear a significantly higher risk (OR 3.432; 95% CI [1.297–9.082]; p = 0.013) of displaying pathological white matter hyperintensities. As expected, aging, hypertension and cardiovascular and dementia risk scales were also positively associated to pathological white matter hyperintensities, but these did not modulate the effect of APOE-ɛ4/ɛ4. In subjects at genetic risk of developing Alzheimer's disease, the control of modifiable risk factors of white matter hyperintensities is of particular relevance to reduce or delay dementia’s onset. [ABSTRACT FROM AUTHOR]

Background: Gray matter changes associated with the progression of Alzheimer's disease (AD) have been thoroughly studied. However, alterations in white matter tracts have received less attention, particularly during early or preclinical stages of the disease.Objective: To identify the structural connectivity changes across the AD continuum.Methods: We performed probabilistic tractography in a total of 183 subjects on two independent samples that include control (n = 68) and preclinical AD individuals (n = 28), patients diagnosed with mild cognitive impairment (MCI) due to AD (n = 44), and AD patients (n = 43). We compared the connectivity between groups, and with CSF Aβ42 and tau biomarkers.Results: We observed disconnections in preclinical individuals, mainly located in the temporal lobe. This pattern of disconnection spread to the parietal and frontal lobes at the MCI stage and involved almost all the brain in AD. These findings were not driven by gray matter atrophy.Discussion: Using tractography, we were able to identify white matter changes between subsequent disease stages and, notably, also in preclinical AD. Therefore, this method may be useful for detecting early and specific brain structural changes during preclinical AD stage. [ABSTRACT FROM AUTHOR]

Analysis of the structural connectomes can lead to powerful insights about the brain's organization and damage. However, the accuracy and reproducibility of constructing the structural connectome done with different acquisition and reconstruction techniques is not well defined. In this work, we evaluated the reproducibility of the structural connectome techniques by performing test-retest (same day) and longitudinal studies (after 1 month) as well as analyzing graph-based measures on the data acquired from 22 healthy volunteers (6 subjects were used for the longitudinal study). We compared connectivity matrices and tract reconstructions obtained with the most typical acquisition schemes used in clinical application: diffusion tensor imaging (DTI), high angular resolution diffusion imaging (HARDI), and diffusion spectrum imaging (DSI). We observed that all techniques showed high reproducibility in the test-retest analysis (correlation >.9). However, HARDI was the only technique with low variability (2%) in the longitudinal assessment (1-month interval). The intraclass coefficient analysis showed the highest reproducibility for the DTI connectome, however, with more sparse connections than HARDI and DSI. Qualitative (neuroanatomical) assessment of selected tracts confirmed the quantitative results showing that HARDI managed to detect most of the analyzed fiber groups and fanning fibers. In conclusion, we found that HARDI acquisition showed the most balanced trade-off between high reproducibility of the connectome, higher rate of path detection and of fanning fibers, and intermediate acquisition times (10-15 minutes), although at the cost of higher appearance of aberrant fibers. [ABSTRACT FROM AUTHOR]

Background: Corpus callosum (CC) is a common target for multiple sclerosis (MS) pathology. We investigated the influence of CC damage on physical disability and cognitive dysfunction using a multimodal approach. Methods: Twenty-one relapsing-remitting MS patients and 13 healthy controls underwent structural MRI and diffusion tensor of the CC (fractional anisotropy; mean diffusivity, MD; radial diffusivity, RD; axial diffusivity). Interhemisferic transfer of motor inhibition was assessed by recording the ipsilateral silent period (iSP) to transcranial magnetic stimulation. We evaluated cognitive function using the Brief Repeatable Battery and physical disability using the Expanded Disability Status Scale (EDSS) and the MS Functional Composite (MSFC) z-score. Results: The iSP latency correlated with physical disability scores (r ranged from 0.596 to 0.657, P values from 0.004 to 0.001), and with results of visual memory (r =-0.645, P = 0.002), processing speed (r =-0.51, P = 0.018) and executive cognitive domain tests (r =-0.452, P = 0.039). The area of the rostrum correlated with the EDSS (r =-0.442, P = 0.045). MD and RD correlated with cognitive performance, mainly with results of visual and verbal memory tests (r ranged from 20.446 to 20.546, P values from 0.048 to 0.011). The iSP latency correlated with CC area (r =20.345, P = 0.049), volume (r =-0.401, P = 0.002), MD (r = 0.404, P = 0.002) and RD (r = 0.415, P = 0.016). Conclusions: We found evidence for structural and microstructural CC abnormalities associated with impairment of motor callosal inhibitory conduction in MS. CC damage may contribute to cognitive dysfunction and in less extent to physical disability likely through a disconnection mechanism. [ABSTRACT FROM AUTHOR]

Summary Altered pupillary behavior is commonly present during and following epileptic seizures, but symptomatic pupillary hippus as the main feature of a seizure has not been reported in the modern literature. We present the case of a woman with epileptic seizures consisting of sustained fluctuation of perception of brightness. Bilateral pupillary hippus is the main semiologic feature.This autonomic phenomenon is selective for the pupils and does not involve other autonomic-mediated responses. An ictal video illustrates this phenomenon. The epileptogenic region, determined by ictal scalp and intracranial electroencephalography (EEG), is localized in the right posterior parietooccipital areas. Pupillary reflexes can be overridden by cortical input; here authors review the literature and discus the physiologic mechanisms underlying this autonomic phenomenon. Fluctuation in perceptual brightness during epileptic seizures may have a basis in ictal pupillary hippus. [ABSTRACT FROM AUTHOR]

Aim To test T1 intensity variations induced by levodopa administration in the regional fixation area in the human brain. Method Using non-invasive magnetic resonance imaging (MRI) technique [T1-weighted sequence MPRAGE; TE/TR/TI = 5/25/800 ms; impulsion angle = 15°; field of view = 256 × 230 × 180 mm3; acquisition matrix = 256 × 192 × 104; reconstruction matrix = 256 × 256 × 128), we tested changes in the T1 MRI signal intensity resulting in changes in the grey matter automatic classification after administration of a single dose of 100 mg of levodopa by a voxel-based morphometry method (VBM) in 12 healthy subjects. Results The VBM analysis demonstrated an increased number of voxels attributed to grey matter after levodopa administration in an anatomical cluster which included substantia nigra, tegmental ventral area and subthalamic nucleus bilaterally, the principal origin and first relay nuclei of projections in brain dopaminergic systems ( t = 8.61; corrected for all grey matter volume P < 0.001). Conclusion Our results suggest that levodopa administration could induce an MRI T1 signal intensity variation that is not evident to the naked eye, but is detectable by measuring local signal intensities. Possible clinical applications are discussed. [ABSTRACT FROM AUTHOR]

Background: Magnetic resonance imaging (MRI) has unveiled specific alterations at different stages of Alzheimer's disease (AD) pathophysiologic continuum constituting what has been established as "AD signature". To what extent MRI can detect amyloid-related cerebral changes from structural MRI in cognitively unimpaired individuals is still an area open for exploration. Method: Longitudinal 3D-T1 MRI scans were acquired from a subset of the ADNI cohort comprising 403 subjects: 79 controls (Ctrls), 50 preclinical AD (PreAD), and 274 MCI and dementia due to AD (MCI/AD). Amyloid CSF was used as gold-standard measure with established cutoffs (< 192 pg/mL) to establish diagnostic categories. Cognitively unimpaired individuals were defined as Ctrls if were amyloid negative and PreAD otherwise. The MCI/AD group was amyloid positive. Only subjects with the same diagnostic category at baseline and follow-up visits were considered for the study. Longitudinal morphometric analysis was performed using SPM12 to calculate Jacobian determinant maps. Statistical analysis was carried out on these Jacobian maps to identify structural changes that were significantly different between diagnostic categories. A machine learning classifier was applied on Jacobian determinant maps to predict the presence of abnormal amyloid levels in cognitively unimpaired individuals. The performance of this classifier was evaluated using receiver operating characteristic curve analysis and as a function of the follow-up time between MRI scans. We applied a cost function to assess the benefit of using this classifier in the triaging of individuals in a clinical trial-recruitment setting. Results: The optimal follow-up time for classification of Ctrls vs PreAD was Δt > 2.5 years, and hence, only subjects within this temporal span are used for evaluation (15 Ctrls, 10 PreAD). The longitudinal voxel-based classifier achieved an AUC = 0.87 (95%CI 0.72–0.97). The brain regions that showed the highest discriminative power to detect amyloid abnormalities were the medial, inferior, and lateral temporal lobes; precuneus; caudate heads; basal forebrain; and lateral ventricles. Conclusions: Our work supports that machine learning applied to longitudinal brain volumetric changes can be used to predict, with high precision, the presence of amyloid abnormalities in cognitively unimpaired subjects. Used as a triaging method to identify a fixed number of amyloid-positive individuals, this longitudinal voxel-wise classifier is expected to avoid 55% of unnecessary CSF and/or PET scans and reduce economic cost by 40%. [ABSTRACT FROM AUTHOR]

Background: White matter hyperintensities (WMH) of presumed vascular origin have been associated with an increased risk of Alzheimer's disease (AD). This study aims to describe the patterns of WMH associated with dementia risk estimates and individual risk factors in a cohort of middle-aged/late middle-aged individuals (mean 58 (interquartile range 51–64) years old). Methods: Magnetic resonance imaging and AD risk factors were collected from 575 cognitively unimpaired participants. WMH load was automatically calculated in each brain lobe and in four equidistant layers from the ventricular surface to the cortical interface. Global volumes and regional patterns of WMH load were analyzed as a function of the Cardiovascular Risk Factors, Aging and Incidence of Dementia (CAIDE) dementia risk score, as well as family history of AD and Apolipoprotein E (APOE) genotype. Additional analyses were performed after correcting for the effect of age and hypertension. Results: The studied cohort showed very low WMH burden (median 1.94 cm3) and 20-year dementia risk estimates (median 1.47 %). Even so, higher CAIDE scores were significantly associated with increased global WMH load. The main drivers of this association were age and hypertension, with hypercholesterolemia and body mass index also displaying a minor, albeit significant, influence. Regionally, CAIDE scores were positively associated with WMH in anterior areas, mostly in the frontal lobe. Age and hypertension showed significant association with WMH in almost all regions analyzed. The APOE-ε2 allele showed a protective effect over global WMH with a pattern that comprised juxtacortical temporo-occipital and fronto-parietal deep white matter regions. Participants with maternal family history of AD had higher WMH load than those without, especially in temporal and occipital lobes. Conclusions: WMH load is associated with AD risk factors even in cognitively unimpaired subjects with very low WMH burden and dementia risk estimates. Our results suggest that tight control of modifiable risk factors in middle-age/late middle-age could have a significant impact on late-life dementia. [ABSTRACT FROM AUTHOR]