Longitudinal Neuroimaging Study Research Articles

G.P.130: Tracking the brain in myotonic dystrophy: A 5-year longitudinal neuroimaging and neuropsychological follow-up study

It is unknown whether brain affection in myotonic dystrophy type 1 (DM1) and 2 (DM2) is due to neurodevelopmental defects, neurodegeneration or both. Longitudinal imaging studies are missing to date. We performed a longitudinal study to compare changes in cognitive functioning and brain morphology including 16 DM1 (m/f: 6/10, age at baseline 42.48 ± 6.46 years/y, disease duration/DD 13.4 ± 7.5 y), 16 DM2 patients (m/f: 9/7, age 48.49 ± 8.36 y, DD 11.4 ± 9.1 y), and 17 healthy controls (m/f: 9/8, age 50.54 ± 9.78 y). At baseline and 5.45 ± 0.41 y follow-up all subjects underwent neurological and neuropsychological (NP) examinations and 3T-brain magnetic resonance imaging using the identical hard- and software. Diffusion tensor imaging (DTI, Tract Based Spatial Statistics) was conducted to analyse white matter (WM) affection with respect to fractional anisotropy (FA), axial, radial, and mean diffusivity. We used 2-sample t-tests (TT) for group comparisons between patients and controls, and paired t -tests (PT) for longitudinal analyses within each group ( p

Progressive Reduction in Cortical Thickness as Psychosis Develops: A Multisite Longitudinal Neuroimaging Study of Youth at Elevated Clinical Risk

BackgroundIndividuals at clinical high risk (CHR) who progress to fully psychotic symptoms have been observed to show a steeper rate of cortical gray matter reduction compared with individuals without symptomatic progression and with healthy control subjects. Whether such changes reflect processes associated with the pathophysiology of schizophrenia or exposure to antipsychotic drugs is unknown. MethodsIn this multisite study, 274 CHR cases, including 35 individuals who converted to psychosis, and 135 healthy comparison subjects were scanned with magnetic resonance imaging at baseline, 12-month follow-up, or the point of conversion for the subjects who developed fully psychotic symptoms. ResultsIn a traveling subjects substudy, excellent reliability was observed for measures of cortical thickness and subcortical volumes. Controlling for multiple comparisons throughout the brain, CHR subjects who converted to psychosis showed a steeper rate of gray matter loss in the right superior frontal, middle frontal, and medial orbitofrontal cortical regions as well as a greater rate of expansion of the third ventricle compared with CHR subjects who did not convert to psychosis and healthy control subjects. Differential tissue loss was present in subjects who had not received antipsychotic medications during the interscan interval and was predicted by baseline levels of an aggregate measure of proinflammatory cytokines in plasma. ConclusionsThese findings demonstrate that the brain changes are not explained by exposure to antipsychotic drugs but likely play a role in psychosis pathophysiology. Given that the cortical changes were more pronounced in subjects with briefer durations of prodromal symptoms, contributing factors may predominantly play a role in acute-onset forms of psychosis.

Relationship between working‐memory network function and substance use: a 3‐year longitudinal fMRI study in heavy cannabis users and controls

Deficient executive functions play an important role in the development of addiction. Working-memory may therefore be a powerful predictor of the course of drug use, but chronic substance use may also impair working-memory. The aim of this 3-year longitudinal neuro-imaging study was to investigate the relationship between substance use (e.g. alcohol, cannabis, nicotine, illegal psychotropic drugs) and working-memory network function over time in heavy cannabis users and controls. Forty-nine participants performed an n-back working-memory task at baseline and at 3-year follow-up. At follow-up, there were 22 current heavy cannabis users, 4 abstinent heavy cannabis users and 23 non-cannabis-using controls. Tensor-independent component analysis (Tensor-ICA) was used to investigate individual differences in working-memory network functionality over time. Within the group of cannabis users, cannabis-related problems remained stable, whereas alcohol-related problems, nicotine dependence and illegal psychotropic substance use increased over time. At both measurements, behavioral performance and network functionality during the n-back task did not differ between heavy cannabis users and controls. Although n-back accuracy improved, working-memory network function remained stable over time. Within the group of cannabis users, working-memory network functionality was not associated with substance use. These results suggest that sustained moderate to heavy levels of cannabis, nicotine, alcohol and illegal psychotropic substance use do not change working-memory network functionality. Moreover, baseline network functionality did not predict cannabis use and related problems three years later, warranting longitudinal studies in more chronic or dependent cannabis users.

Changes of amygdalae in systemic lupus patients with epilepsy

WCN 2013 No: 1807 Topic: 1 — Epilepsy Changes of amygdalae in systemic lupus patients with epilepsy K. Peterova, V. Peterova, R. Svobodova, S.S. Pesickova, M. Fojtikova, P. Petrovický. Dept. of Neurology, Charles University in Prague, 1st Faculty of Medicine, Prague, Czech Republic; MR Dept., Radiodiagnostic Clinic, Charles University in Prague, 1st Faculty of Medicine, Prague, Czech Republic; Institute of Rheumatology, Charles University in Prague, 1st Faculty of Medicine, Prague, Czech Republic; Dept. of Nephrology, Charles University in Prague, 1st Faculty of Medicine, Prague, Czech Republic; Institute of Anatomy, Charles University in Prague, 1st Faculty ofMedicine, Prague, Czech Republic Objective: To analyze slight changes of amygdalae and their volumetry in systemic lupus erythematosus (SLE) patients with neuropsychiatric symptomatology (NP-SLE), because disability of amygdalae and changes in size and activity had been reported in patients with depression and mood disorders, in some studies it even correlated with the severity of depressive episodes. NP-SLE includes mood disorders, cognitive deficits up to dementia, stroke, epilepsy etc. We performed amygdalar volumetry by semiautomatic method in special software, using manual contoured rims in sequence using thin slices. Methods: We investigated 23 female patients with proven NP-SLE, aged 19 to 67 years, whichwere recruited for a prospective longitudinal neuroimaging study conducted at 1.5T MR device. Findings were statistically processed and compared with corresponding healthy persons. Results: In our study we found, that in patients with active NP-SLE right amygdala correlated from all monitored parameters only with the left amygdala (p = 0.01), left amygdala correlated with right amygdala (p = 0.01) and with volumetry in flow attenuation inversion recovery (FLAIR) and T1 weighted images (p = 0.05). Conclusions: We failed to demonstrate significant volume change in amygdalae in the sample of NP-SLE patients. We did not demonstrate significant difference of amygdalar volume due to the duration of NP-SLE or age of the patients. The authors' research was supported by the research project MZO 0006416 and 000 00

Developmental changes in the structure of the social brain in late childhood and adolescence

Social cognition provides humans with the necessary skills to understand and interact with one another. One aspect of social cognition, mentalizing, is associated with a network of brain regions often referred to as the 'social brain.' These consist of medial prefrontal cortex [medial Brodmann Area 10 (mBA10)], temporoparietal junction (TPJ), posterior superior temporal sulcus (pSTS) and anterior temporal cortex (ATC). How these specific regions develop structurally across late childhood and adolescence is not well established. This study examined the structural developmental trajectories of social brain regions in the longest ongoing longitudinal neuroimaging study of human brain maturation. Structural trajectories of grey matter volume, cortical thickness and surface area were analyzed using surface-based cortical reconstruction software and mixed modeling in a longitudinal sample of 288 participants (ages 7-30 years, 857 total scans). Grey matter volume and cortical thickness in mBA10, TPJ and pSTS decreased from childhood into the early twenties. The ATC increased in grey matter volume until adolescence and in cortical thickness until early adulthood. Surface area for each region followed a cubic trajectory, peaking in early or pre-adolescence before decreasing into the early twenties. These results are discussed in the context of developmental changes in social cognition across adolescence.

Visual functional magnetic resonance imaging of preterm infants

The aim of this study was to determine the feasibility of undertaking visual functional magnetic resonance imaging (fMRI) in very preterm children. Forty-seven infants born at less than 32 weeks gestational age (25 males, 22 females; mean (SD) age at birth 28.8 wks [1.9]) were scanned using 1.5 T MRI as part of a longitudinal neuroimaging study. These infants were scanned at preterm age (within 2 wks of birth) and at term-equivalent age. Quantitative T2* data and fMRI in response to visual stimuli (flashing strobe) were acquired in this population. T2* values were compared at preterm age and at term-equivalent age using a two-tailed t-test. A general linear model was used to evaluate occipital lobe response to visual stimuli. T2* values were significantly higher at preterm age than at term-equivalent age in both the medial and lateral occipital lobes (preterm infants: 187.2 ms and 198.4 ms respectively; term infants: 110.9 ms and 133.2 ms respectively; p<0.002). Significant positive occipital lobe activation (q<0.01) was found in 3 out of 65 (5%) fMRIs carried out at preterm age and in 19 out of 26 (73%) scans carried out at term-equivalent age. Visual stimuli do not elicit a reliable blood oxygen level-dependent (BOLD) response in very preterm infants during the preterm period. This suggests that BOLD fMRI may not be the appropriate modality for investigating occipital lobe function in very preterm infants.

Frontal gray matter reduction after breast cancer chemotherapy and association with executive symptoms: a replication and extension study.

Cognitive changes related to cancer and its treatment have been intensely studied, and neuroimaging has begun to demonstrate brain correlates. In the first prospective longitudinal neuroimaging study of breast cancer (BC) patients we recently reported decreased gray matter density one month after chemotherapy completion, particularly in frontal regions. These findings helped confirm a neural basis for previously reported cognitive symptoms, which most commonly involve executive and memory processes in which the frontal lobes are a critical component of underlying neural circuitry. Here we present data from an independent, larger, more demographically diverse cohort that is more generalizable to the BC population. BC patients treated with (N=27) and without (N=28) chemotherapy and matched healthy controls (N=24) were scanned at baseline (prior to systemic treatment) and one month following chemotherapy completion (or yoked intervals for non-chemotherapy and control groups) and APOE-genotyped. Voxel-based morphometry (VBM) showed decreased frontal gray matter density after chemotherapy, as observed in the prior cohort, which was accompanied by self-reported difficulties in executive functioning. Gray matter and executive symptom changes were not related to APOE ε4 status, though a somewhat greater percentage of BC patients who received chemotherapy were ε4 allele carriers than patients not treated with chemotherapy or healthy controls. These findings provide confirmatory evidence of frontal morphometric changes that may be a pathophysiological basis for cancer and treatment-related cognitive dysfunction. Further research into individual risk factors for such changes will be critical for development of treatment and prevention strategies.

Patterns of Coordinated Anatomical Change in Human Cortical Development: A Longitudinal Neuroimaging Study of Maturational Coupling

Understanding of human structural brain development has rapidly advanced in recent years, but remains fundamentally "localizational" in nature. Here, we use 376 longitudinally acquired structural brain scans from 108 typically developing adolescents to conduct the first study of coordinated anatomical change within the developing cortex. Correlation in rates of anatomical change was regionally heterogeneous, with fronto-temporal association cortices showing the strongest and most widespread maturational coupling with other cortical areas, and lower-order sensory cortices showing the least. Canonical cortical systems with rich structural and functional interconnectivity showed significantly elevated maturational coupling. Evidence for sexually dimorphic maturational coupling was found within a frontopolar-centered prefrontal system involved in complex decision-making. By providing the first link between cortical connectivity and the coordination of cortical development, we reveal a hitherto unseen property of healthy brain maturation, which may represent a target for neurodevelopmental disease processes, and a substrate for sexually dimorphic behavior in adolescence.

The Neurobiological Role of the Dorsolateral Prefrontal Cortex in Recovery From Trauma

A multiwave longitudinal neuroimaging study in a cohort of direct survivors of a South Korean subway disaster, most of whom recovered from posttraumatic stress disorder 5 years after trauma, provided a unique opportunity to investigate the brain correlates of recovery from a severe psychological trauma. To investigate region-specific brain mobilization during successful recovery from posttraumatic stress disorder by assessing cortical thickness multiple times from early after trauma to recovery, and to examine whether a brain-derived neurotrophic factor gene polymorphism was associated with this brain mobilization. Five-year follow-up case-control study conducted from 2003-2007. Seoul National University and Hospital. Thirty psychologically traumatized disaster survivors and 36 age- and sex-matched control group members recruited from the disaster registry and local community, respectively, who contributed 156 high-resolution brain magnetic resonance images during 3 waves of assessments. Cerebral cortical thickness measured in high-resolution anatomic magnetic resonance images using a validated cortical thickness analysis tool and its prospective changes from early after trauma to recovery in trauma-exposed individuals and controls. Trauma-exposed individuals had greater dorsolateral prefrontal cortical (DLPFC) thickness 1.42 years after trauma (right DLPFC, 5.4%; left superior frontal cortex, 5.8%; and left inferior frontal cortex, 5.3% [all clusters, P≤.01]) relative to controls. Thicknesses gradually normalized over time during recovery. We found a positive linear trend, with trauma-exposed individuals with a valine/valine genotype having the greatest DLPFC cortical thickness, followed by those with a methionine genotype and controls (P<.001 for trend). Greater DLPFC thickness was associated with greater posttraumatic stress disorder symptom reductions and better recovery. The DLPFC region might play an important role in psychological recovery from a severely traumatic event in humans.

Evolution of crossmodal reorganization of the voice area in cochlear‐implanted deaf patients

Psychophysical and neuroimaging studies in both animal and human subjects have clearly demonstrated that cortical plasticity following sensory deprivation leads to a brain functional reorganization that favors the spared modalities. In postlingually deaf patients, the use of a cochlear implant (CI) allows a recovery of the auditory function, which will probably counteract the cortical crossmodal reorganization induced by hearing loss. To study the dynamics of such reversed crossmodal plasticity, we designed a longitudinal neuroimaging study involving the follow-up of 10 postlingually deaf adult CI users engaged in a visual speechreading task. While speechreading activates Broca's area in normally hearing subjects (NHS), the activity level elicited in this region in CI patients is abnormally low and increases progressively with post-implantation time. Furthermore, speechreading in CI patients induces abnormal crossmodal activations in right anterior regions of the superior temporal cortex normally devoted to processing human voice stimuli (temporal voice-sensitive areas-TVA). These abnormal activity levels diminish with post-implantation time and tend towards the levels observed in NHS. First, our study revealed that the neuroplasticity after cochlear implantation involves not only auditory but also visual and audiovisual speech processing networks. Second, our results suggest that during deafness, the functional links between cortical regions specialized in face and voice processing are reallocated to support speech-related visual processing through cross-modal reorganization. Such reorganization allows a more efficient audiovisual integration of speech after cochlear implantation. These compensatory sensory strategies are later completed by the progressive restoration of the visuo-audio-motor speech processing loop, including Broca's area.

Functional regression via variational Bayes

We introduce variational Bayes methods for fast approximate inference in functional regression analysis. Both the standard cross-sectional and the increasingly common longitudinal settings are treated. The methodology allows Bayesian functional regression analyses to be conducted without the computational overhead of Monte Carlo methods. Confidence intervals of the model parameters are obtained both using the approximate variational approach and nonparametric resampling of clusters. The latter approach is possible because our variational Bayes functional regression approach is computationally efficient. A simulation study indicates that variational Bayes is highly accurate in estimating the parameters of interest and in approximating the Markov chain Monte Carlo-sampled joint posterior distribution of the model parameters. The methods apply generally, but are motivated by a longitudinal neuroimaging study of multiple sclerosis patients. Code used in simulations is made available as a web-supplement.

Imaging systems level consolidation of novel associate memories: A longitudinal neuroimaging study

Previously, a standard theory of systems level memory consolidation was developed to describe how memory recall becomes independent of the medial temporal memory system. More recently, an extended consolidation theory was proposed that predicts seven changes in regional neural activity and inter-regional functional connectivity. Using longitudinal event-related functional magnetic resonance imaging of an associate memory task, we simultaneously tested all predictions and additionally tested for consolidation-related changes in recall of associate memories at a sub-trial temporal resolution, analyzing cue, delay and target periods of each trial separately. Results consistent with the theoretical predictions were observed though two inconsistent results were also obtained. In particular, while medial temporal recall related delay period activity decreased with consolidation as predicted, visual cue activity increased for consolidated memories. Though the extended theory of memory consolidation is largely supported by our study, these results suggest that the extended theory needs further refinement and the medial temporal memory system has multiple, temporally distinct roles in associate memory recall. Neuroimaging analysis at a sub-trial temporal resolution, as used here, may further clarify the role of the hippocampal complex in memory consolidation.

Sexual dimorphism of brain developmental trajectories during childhood and adolescence

Human total brain size is consistently reported to be ∼ 8–10% larger in males, although consensus on regionally specific differences is weak. Here, in the largest longitudinal pediatric neuroimaging study reported to date (829 scans from 387 subjects, ages 3 to 27 years), we demonstrate the importance of examining size-by-age trajectories of brain development rather than group averages across broad age ranges when assessing sexual dimorphism. Using magnetic resonance imaging (MRI) we found robust male/female differences in the shapes of trajectories with total cerebral volume peaking at age 10.5 in females and 14.5 in males. White matter increases throughout this 24-year period with males having a steeper rate of increase during adolescence. Both cortical and subcortical gray matter trajectories follow an inverted U shaped path with peak sizes 1 to 2 years earlier in females. These sexually dimorphic trajectories confirm the importance of longitudinal data in studies of brain development and underline the need to consider sex matching in studies of brain development.

One-year age changes in MRI brain volumes in older adults.

Longitudinal studies indicate that declines in cognition and memory accelerate after age 70 years. The neuroanatomic and neurophysiologic underpinnings of cognitive change are unclear, as there is little information on longitudinal brain changes. We are conducting a longitudinal neuroimaging study of nondemented older participants in the Baltimore Longitudinal Study of Aging. This report focuses on age and sex differences in brain structure measured by magnetic resonance imaging during the first two annual evaluations. Cross-sectional results from 116 participants aged 59-85 years reveal significantly larger ventricular volumes and smaller gray and white matter volumes in older compared with younger participants and in men compared with women. Regional brain volumes show that the effects of age and sex are not uniform across brain regions. Age differences are greatest for the parietal region. Sex differences tend to be larger for frontal and temporal than parietal and occipital regions. Longitudinal analysis demonstrates an increase of 1526 mm(3) in ventricular volume over 1 year, but no detectable change in total or regional brain volumes. Definition of the pattern and rate of longitudinal brain changes will facilitate the detection of pathological brain changes, which may be predictors of dementia.