Longitudinal Magnetic Resonance Imaging Study Research Articles

Patterns of regional gray matter loss at different stages of schizophrenia: A multisite, cross-sectional VBM study in first-episode and chronic illness.

Background: Structural brain abnormalities in schizophrenia have been repeatedly demonstrated in magnetic resonance imaging (MRI) studies, but it remains unclear whether these are static or progressive in nature. While longitudinal MRI studies have been traditionally used to assess the issue of progression of brain abnormalities in schizophrenia, information from cross-sectional neuroimaging studies directly comparing first-episode and chronic schizophrenia patients to healthy controls may also be useful to further clarify this issue. With the recent interest in multisite mega-analyses combining structural MRI data from multiple centers aiming at increased statistical power, the present multisite voxel-based morphometry (VBM) study was carried out to examine patterns of brain structural changes according to the different stages of illness and to ascertain which (if any) of such structural abnormalities would be specifically correlated to potential clinical moderators, including cumulative exposure to antipsychotics, age of onset, illness duration and overall illness severity.Methods: We gathered a large sample of schizophrenia patients (161, being 99 chronic and 62 first-episode) and controls (151) from four previous morphometric MRI studies (1.5 T) carried out in the same geographical region of Brazil. Image processing and analyses were conducted using Statistical Parametric Mapping (SPM8) software with the diffeomorphic anatomical registration through exponentiated Lie algebra (DARTEL) algorithm. Group effects on regional gray matter (GM) volumes were investigated through whole-brain voxel-wise comparisons using General Linear Model Analysis of Co-variance (ANCOVA), always including total GM volume, scan protocol, age and gender as nuisance variables. Finally, correlation analyses were performed between the aforementioned clinical moderators and regional and global brain volumes.Results: First-episode schizophrenia subjects displayed subtle volumetric deficits relative to controls in a circumscribed brain regional network identified only in small volume-corrected (SVC) analyses (p < 0.05, FWE-corrected), including the insula, temporolimbic structures and striatum. Chronic schizophrenia patients, on the other hand, demonstrated an extensive pattern of regional GM volume decreases relative to controls, involving bilateral superior, inferior and orbital frontal cortices, right middle frontal cortex, bilateral anterior cingulate cortices, bilateral insulae and right superior and middle temporal cortices (p < 0.05, FWE-corrected over the whole brain). GM volumes in several of those brain regions were directly correlated with age of disease onset on SVC analyses for conjoined (first-episode and chronic) schizophrenia groups. There were also widespread foci of significant negative correlation between duration of illness and relative GM volumes, but such findings remained significant only for the right dorsolateral prefrontal cortex after accounting for the influence of age of disease onset. Finally, significant negative correlations were detected between life-time cumulative exposure to antipsychotics and total GM and white matter volumes in schizophrenia patients, but no significant relationship was found between indices of antipsychotic usage and relative GM volume in any specific brain region.Conclusion: The above data indicate that brain changes associated with the diagnosis of schizophrenia are more widespread in chronic schizophrenia compared to first-episode patients. Our findings also suggest that relative GM volume deficits may be greater in (presumably more severe) cases with earlier age of onset, as well as varying as a function of illness duration in specific frontal brain regions. Finally, our results highlight the potentially complex effects of the continued use of antipsychotic drugs on structural brain abnormalities in schizophrenia, as we found that cumulative doses of antipsychotics affected brain volumes globally rather than selectively on frontal-temporal regions.

Progression of lumbar disc herniations over an eight-year period in a group of adult Danes from the general population--a longitudinal MRI study using quantitative measures.

BackgroundA lumbar disc herniation (LDH) is a localised displacement of disc material, which may initiate changes in the disc and adjacent structures such as the nerve root and the spinal canal. Knowledge about how morphological changes in the disc relate to changes in other spinal structures might give the clinician a better understanding of the natural history and consequences of lumbar disc herniations. However, few longitudinal studies have investigated this process using reliable measures from magnetic resonance imaging (MRI). The objectives of this study were to examine changes in and associations between the size of lumbar disc herniations, dural sac area and disc height over an eight-year period using MRI at three time-points.MethodsIndividuals from a population-based cohort, the ‘Backs on Funen Cohort’, had MRIs taken at age 41 years and again at 45 and 49 years. Only disc levels with MRI-confirmed disc herniations at 41 or 45 years were included. Cross-sectional areas (mm2) of the LDH, dural sac and disc height were calculated from measurements performed on sagittal T2-weighted images using a previously validated method. Changes over time for the three MRI findings were defined as “unchanged”, “increased “, “decreased”, or “fluctuating”. Only changes beyond 95 % limits of agreement of the same measurements were regarded as valid. Associations between the three types of measures were examined cross-sectionally and longitudinally.ResultsOne hundred and forty disc levels, from 106 people (48 women and 58 men), were included. Over eight years, 65 % of the herniations remained unchanged, 17.5 % decreased, 12.5 % increased, and 5 % had a fluctuating pattern. Increased herniation size was associated with decreased dural sac area (β-0.25[−0.52;0.01]) and increased disc height (β 0.35[0.14;0.56]). Moreover, larger herniation size predicted a statistically significant reduction in both dural sac area (β-0.35[−0.58;-0.13]) and disc height (β-0.50[−0.81;-0.20]).ConclusionsOn average, most LDHs do not change over a four- to eight-year period. However, larger herniation size predicts a reduction in both dural sac area and disc height. Further research should be done to determine the correlations between the progression of LDH and resolution of patient symptoms.

Tracking Parkinson's Disease over One Year with Multimodal Magnetic Resonance Imaging in a Group of Older Patients with Moderate Disease.

Background & ObjectivesCross-sectional magnetic resonance imaging (MRI) suggests that Parkinson’s disease (PD) is associated with changes in cerebral tissue volume, diffusion tensor imaging metrics, and perfusion values. Here, we performed a longitudinal multimodal MRI study—including structural, diffusion tensor imaging (DTI), and perfusion MRI—to investigate progressive brain changes over one year in a group of older PD patients at a moderate stage of disease.MethodsTwenty-three non-demented PD (mean age (SD) = 69.5 (6.4) years, disease duration (SD) = 5.6 (4.3) years) and 23 matched control participants (mean age: 70.6 (6.8)) completed extensive neuropsychological and clinical assessment, and multimodal 3T MRI scanning at baseline and one year later. We used a voxel-based approach to assess change over time and group-by-time interactions for cerebral structural and perfusion metrics.ResultsCompared to controls, in PD participants there was localized grey matter atrophy over time in bilateral inferior and right middle temporal, and left orbito-frontal cortices. Using a voxel-based approach that focused on the centers of principal white matter tracts, the PD and control cohorts exhibited similar levels of change in DTI metrics. There was no significant change in perfusion, cognitive, or motor severity measures.ConclusionsIn a cohort of older, non-demented PD participants, macrostructural MRI detected atrophy in the PD group compared with the control group in temporal and orbito-frontal cortices. Changes in diffusion MRI along principal white matter tracts over one year were found, but this was not differentially affected by PD.

Longitudinal magnetic resonance imaging study shows progressive pyramidal and callosal damage in Friedreich's ataxia

Spinal cord and peripheral nerves are classically known to be damaged in Friedreich's ataxia, but the extent of cerebral involvement in the disease and its progression over time are not yet characterized. The aim of this study was to evaluate longitudinally cerebral damage in Friedreich's ataxia. We enrolled 31 patients and 40 controls, which were evaluated at baseline and after 1 and 2 years. To assess gray matter, we employed voxel-based morphometry and cortical thickness measurements. White matter was evaluated using diffusion tensor imaging. Statistical analyses were both cross-sectional and longitudinal (corrected for multiple comparisons). Group comparison between patients and controls revealed widespread macrostructural differences at baseline: gray matter atrophy in the dentate nuclei, brainstem, and precentral gyri; and white matter atrophy in the cerebellum and superior cerebellar peduncles, brainstem, and periventricular areas. We did not identify any longitudinal volumetric change over time. There were extensive microstructural alterations, including superior cerebellar peduncles, corpus callosum, and pyramidal tracts. Longitudinal analyses identified progressive microstructural abnormalities at the corpus callosum, pyramidal tracts, and superior cerebellar peduncles after 1 year of follow-up. Patients with Friedreich's ataxia present more widespread gray and white matter damage than previously reported, including not only infratentorial areas, but also supratentorial structures. Furthermore, patients with Friedreich's ataxia have progressive microstructural abnormalities amenable to detection in a short-term follow-up.

No progressive brain changes during a 1-year follow-up of patients with first-episode psychosis.

First-episode psychosis (FEP) patients show structural brain abnormalities. Whether the changes are progressive or not remain under debate, and the results from longitudinal magnetic resonance imaging (MRI) studies are mixed. We investigated if FEP patients showed a different pattern of regional brain structural change over a 1-year period compared with healthy controls, and if putative changes correlated with clinical characteristics and outcome. MRIs of 79 FEP patients [SCID-I-verified diagnoses: schizophrenia, psychotic bipolar disorder, or other psychoses, mean age 27.6 (s.d. = 7.7) years, 66% male] and 82 healthy controls [age 29.3 (s.d. = 7.2) years, 66% male] were acquired from the same 1.5 T scanner at baseline and 1-year follow-up as part of the Thematically Organized Psychosis (TOP) study, Oslo, Norway. Scans were automatically processed with the longitudinal stream in FreeSurfer that creates an unbiased within-subject template image. General linear models were used to analyse longitudinal change in a wide range of subcortical volumes and detailed thickness and surface area estimates across the entire cortex, and associations with clinical characteristics. FEP patients and controls did not differ significantly in annual percentage change in cortical thickness or area in any cortical region, or in any of the subcortical structures after adjustment for multiple comparisons. Within the FEP group, duration of untreated psychosis, age at illness onset, antipsychotic medication use and remission at follow-up were not related to longitudinal brain change. We found no significant longitudinal brain changes over a 1-year period in FEP patients. Our results do not support early progressive brain changes in psychotic disorders.

Antipsychotics Linked to Cortical Loss in Patients With Schizophrenia

Back to table of contents Previous article Next article Clinical and Research NewsFull AccessAntipsychotics Linked to Cortical Loss in Patients With SchizophreniaVabren WattsVabren WattsSearch for more papers by this authorPublished Online:28 Sep 2015https://doi.org/10.1176/appi.pn.2015.10a14AbstractThough antipsychotic use in patients with schizophrenia was found to be associated with reduction in cortical gray matter volume, first-generation antipsychotics may cause greater reduction than second-generation antipsychotics.Although it is well established that patients with schizophrenia have deficits in cortical gray matter, a meta-analysis published in the September issue of Biological Psychiatry suggests that cumulative antipsychotic intake and the type of antipsychotic a patient with schizophrenia takes may influence the degree of gray matter loss over time.Triff/ShutterstockResearchers from the Department of Mental Health at the University of Brescia School of Medicine in Italy led a retrospective study to determine whether changes in cortical gray matter differ between patients with schizophrenia who take first-generation antipsychotics and those who take second-generation antipsychotics.“The role played by antipsychotic treatment on the pathophysiologic trajectory of brain abnormalities in schizophrenia is currently a matter of lively debate,” explained the study’s lead author, Antonio Vita, M.D., Ph.D., a professor of psychiatry at the University of Brescia, in an interview with Psychiatric News. As Vita and his colleagues noted in the paper, qualitative reviews and independent studies addressing the topic of structural brain changes in schizophrenia in relation to antipsychotic treatment have yielded inconclusive results, with few looking at whether a patient was prescribed first-generation or second-generation antipsychotics.To evaluate the influence of antipsychotic treatment on cortical gray matter volume in patients with schizophrenia, the researchers compiled data from 18 longitudinal magnetic resonance imaging studies, published from January 1, 1983, to March 31, 2014, totaling 1,155 patients with schizophrenia and 911 healthy controls. The results showed that patients with schizophrenia showed significantly greater loss of total cortical gray matter volume than healthy controls, which was related to cumulative antipsychotic intake during the interval between imaging scans among the longitudinal studies. When comparing changes in cortical gray matter volumes in patients who were treated with first-generation antipsychotics (FGAs) with those who were treated with second-generation antipsychotics (SGAs), the researchers found that greater gray matter loss was correlated with higher mean daily dose in studies including patients treated with FGAs, whereas less progressive loss was observed in studies including only patients treated with SGAs. “On the whole, our results indicate that the putative contributory role of antipsychotic treatment in reducing the volume of cortical [gray matter] in schizophrenia cannot be generalized and appears to be less evident for SGAs, which seem to be associated with less loss of brain tissue,” the study authors wrote.Vita told Psychiatric News that many issues remain to be clarified. “We still do not know whether the effects on the brain of antipsychotics vary as a function of age and stage of illness, or whether they may occur only when a certain threshold of exposure [daily dose or cumulative dose] is reached,” said Vita. He concluded that “clarification of these issues will have crucial importance in the clinical management of schizophrenia and will allow a better understanding of the mechanisms underlying the progression of structural brain abnormalities in schizophrenia.”The study was funded by a grant from the Lombardia Region. ■“The Effect of Antipsychotic Treatment on Cortical Gray Matter Changes in Schizophrenia: Does the Class Matter? A Meta-analysis and Meta-regression of Longitudinal Magnetic Resonance Imaging Studies” can be accessed here. ISSUES NewArchived

Longitudinal Changes in Prefrontal Cortex Activation Underlie Declines in Adolescent Risk Taking.

Adolescence is a developmental period marked by steep increases in risk-taking behavior coupled with dramatic brain changes. Although theories propose that the prefrontal cortex (PFC) may influence adolescent risk taking, the specific ways in which it functions remain unclear. We report the first longitudinal functional magnetic resonance imaging study to examine how neural activation during risk taking changes over time and contributes to adolescents' real-life risk-taking behavior. We find that longitudinal declines in activation of the ventrolateral PFC are linked to declines in adolescent risk taking, whereas the medial PFC influences adolescent risk taking via its functional neural coupling with reward-related regions. This is the first study to identify the mechanism by which different regions of the PFC disparately contribute to declines in risk taking.

Biomimetic phantom for cardiac diffusion MRI.

PurposeDiffusion magnetic resonance imaging (MRI) is increasingly used to characterize cardiac tissue microstructure, necessitating the use of physiologically relevant phantoms for methods development. Existing phantoms are generally simplistic and mostly simulate diffusion in the brain. Thus, there is a need for phantoms mimicking diffusion in cardiac tissue.Materials and MethodsA biomimetic phantom composed of hollow microfibers generated using co‐electrospinning was developed to mimic myocardial diffusion properties and fiber and sheet orientations. Diffusion tensor imaging was carried out at monthly intervals over 4 months at 9.4T. 3D fiber tracking was performed using the phantom and compared with fiber tracking in an ex vivo rat heart.ResultsThe mean apparent diffusion coefficient and fractional anisotropy of the phantom remained stable over the 4‐month period, with mean values of 7.53 ± 0.16 × 10‐4 mm2/s and 0.388 ± 0.007, respectively. Fiber tracking of the 1st and 3rd eigenvectors generated analogous results to the fiber and sheet‐normal direction respectively, found in the left ventricular myocardium.ConclusionA biomimetic phantom simulating diffusion in the heart was designed and built. This could aid development and validation of novel diffusion MRI methods for investigating cardiac microstructure, decrease the number of animals and patients needed for methods development, and improve quality control in longitudinal and multicenter cardiac diffusion MRI studies. J. MAGN. RESON. IMAGING 2016;43:594–600.

Increased Surface Area, but not Cortical Thickness, in a Subset of Young Boys With Autism Spectrum Disorder.

The Autism Phenome Project is the largest, single site, longitudinal magnetic resonance imaging (MRI) study of young children with autism spectrum disorder (ASD). Previous analyses from this cohort have shown that the children with autism have a total brain volume at time 1 (∼3 years of age) that is 6% larger than typically developing (TD) children. This finding is driven primarily by 15% of the boys with ASD that have disproportionate megalencephaly (ASD-DM) or brain size that is 1.5 standard deviations above what would be expected for the child's height. In the current study, cerebral cortical grey matter volume, thickness, and surface area were assayed from MRI scans of 112, 3-year-old boys with ASD and 50 age-matched TD boys. The boys with ASD-DM (n = 17) were analyzed separately from the boys with normal brain size (ASD-N, n = 95). Previous studies of cortical thickness and surface area for ASD children in this age range have come to diametrically different conclusions concerning the significance of cortical thickness vs. surface area. Current analyses indicate that cortical thickness was comparable across the ASD and TD groups. However, surface area was significantly greater in the ASD group compared to the TD group. This result was driven largely by the children with ASD-DM. Even in the ASD-DM group, not all cortical regions demonstrated increased surface area. These results provide strong evidence that the early cortical overgrowth associated with ASD is due primarily to increased surface area and not to increased cortical thickness.

Alteration of brain regional homogeneity of monkeys with spinal cord injury: A longitudinal resting-state functional magnetic resonance imaging study

PurposeTo investigate the longitudinal brain regional homogeneity (ReHo) changes in nonhuman primate after spinal cord injury (SCI) by resting-state functional magnetic resonance imaging (fMRI). MethodsThree adult female rhesus monkeys underwent unilateral thoracic cord injury. A resting-state fMRI examination was performed in the healthy stage and 4, 8, and 12weeks after the injury. The ReHo value of each voxel in the monkey brain was calculated and compared between pre- and post-SCI monkeys with paired t test. The regions of interest (ROIs) in the significantly changed ReHo regions were set. The correlations between the ReHo change and the time after injury were also determined. ResultsCompared with those in healthy period, the ReHo values of the left premotor cortex and the anterior cingulate cortex (ACC) in post-SCI rhesus monkeys significantly increased in 4-week follow-up examinations. The ReHo values of posterior cingulate cortex, left precuneus, left temporal parietooccipital area, and bilateral superior parietal lobules decreased at 8-week follow-up examinations. In 12-week follow-up examinations, the ReHo values of the left postcentral gyrus, right caudate nucleus, and superior temporal gyrus increased. Correlation analysis showed positive correlations between left ACC and the postoperative time. ConclusionSCI can change the regional synchronism of brain activity in sensorimotor system and the default mode network. These findings may help us to understand the potential pathophysiological changes in the central nervous system after SCI.

No progression of the alterations in the cortical thickness of individuals with schizophrenia-spectrum disorder: a three-year longitudinal magnetic resonance imaging study of first-episode patients.

Cortical thickness measurement offers an index of brain development processes. In healthy individuals, cortical thickness is reduced with increasing age and is related to cognitive decline. Cortical thinning has been reported in schizophrenia. Whether cortical thickness changes differently over time in patients and its impact on outcome remain unanswered. Data were examined from 109 patients and 76 healthy controls drawn from the Santander Longitudinal Study of first-episode schizophrenia for whom adequate structural magnetic resonance imaging (MRI) data were available (n = 555 scans). Clinical and cognitive assessments and MRIs were acquired at three regular time points during a 3-year follow-up period. We investigated likely progressive cortical thickness changes in schizophrenia during the first 3 years after initiating antipsychotic treatment. The effects of cortical thickness changes on cognitive and clinical variables were also examined along with the impact of potential confounding factors. There were significant diagnoses × scan time interaction main effects for total cortical thickness (F 1,309.1 = 4.60, p = 0.033) and frontal cortical thickness (F 1,310.6 = 5.30, p = 0.022), reflecting a lesser thinning over time in patients. Clinical and cognitive outcome was not associated with progressive cortical changes during the early years of the illness. Cortical thickness abnormalities do not unswervingly progress, at least throughout the first years of the illness. Previous studies have suggested that modifiable factors may partly account for cortical thickness abnormalities. Therefore, the importance of implementing practical actions that may modify those factors and improve them over the course of the illness should be highlighted.

Circulatory dynamics of the cauda equina in lumbar canal stenosis using dynamic contrast-enhanced magnetic resonance imaging

Background contextThere has been no study regarding the cauda equina circulation of patients with neurogenic intermittent claudication (NIC) in lumbar spinal canal stenosis (LSCS) using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). PurposeThe mechanism responsible for the onset of NIC was investigated using DCE-MRI to examine changes in cauda equina blood flow in patients with LSCS. Study designThis was a retrospective longitudinal registry and magnetic resonance imaging study. Patient sampleThe subjects consisted of 23 patients who had LSCS associated with NIC (stenosis group). Ten asymptomatic volunteers who did not have NIC served as controls (control group). In the LSCS group, the cross-sectional area of the dural sac was < 75 mm2 at the site of most severe stenosis. These patients were further divided into single and double stenosis subgroups. Outcome measuresThe main measures we used were the signal intensity (S-I) ratio and the shape and size of the time intensity (T-I) curves. We compared these between the stenosis and control groups. MethodsAt first, plain T1-weighted MR images were obtained and the lumbar dural sac cross-sectional area was measured using a digitizer. For DCE-MRI, sagittal T1-weighted images of the same slice were acquired continuously for 10 minutes after administration of gadolinium as an intravenous bolus to observe the distribution of contrast medium (gadolinium) in the cauda equina. To objectively evaluate changes in contrast enhancement of the cauda equina at the site of canal stenosis, regions of interest were established. The signal intensity (SI) ratio was calculated to compare the signal intensities before and after contrast enhancement, and time-intensity curves were prepared to investigate changes over time. ResultsThe static imaging findings and the changes of gadolinium uptake showed striking differences between the study and control patients. In the stenosis group, abnormal intrathecal enhancement showed around the site of stenosis on enhanced MR imaging. The SI ratio at the site of canal stenosis had a slower increase in the arterial phase when compared with that in the control group and remained high in the venous phase for up to 10 minutes. Finally, abnormal intrathecal enhancement was visible around the site of stenosis on enhanced MR imaging in all patients. ConclusionsThese clinical data indicate that cauda equina nerve roots in the LSCS patients are pathologic even when symptoms are not elicited in the supine position, suggesting that intraradicular venous congestion and edema themselves do not influence the existence of radicular symptoms.

Reduced blood flow in normal white matter predicts development of leukoaraiosis.

The purpose of this study was to investigate whether low cerebral blood flow (CBF) is associated with subsequent development of white matter hyperintensities (WMH). Patients were included from a longitudinal magnetic resonance (MR) imaging study of minor stroke/transient ischemic attack patients. Images were co-registered and new WMH at 18 months were identified by comparing follow-up imaging with baseline fluid-attenuated inversion recovery (FLAIR). Regions-of-interest (ROIs) were placed on FLAIR images in one of three categories: (1) WMH seen at both baseline and follow-up imaging, (2) new WMH seen only on follow-up imaging, and (3) regions of normal-appearing white matter at both time points. Registered CBF maps at baseline were used to measure CBF in the ROIs. A multivariable model was developed using mixed-effects logistic regression to determine the effect of baseline CBF on the development on new WMH. Forty patients were included. Mean age was 61±11 years, 30% were female. Low baseline CBF, female sex, and presence of diabetes were independently associated with the presence of new WMH on follow-up imaging. The odds of having new WMH on follow-up imaging reduces by 0.61 (95% confidence interval=0.57 to 0.65) for each 1 mL/100 g per minute increase in baseline CBF. We conclude that regions of white matter with low CBF develop new WMH on follow-up imaging.

Concussion in Women

INTRODUCTION: Since the enactment of Title IX (1972), rates of female participation in sports have grown exponentially. However, despite these growing numbers, women are infrequently asked about risk factors for and consequences of concussion in the ambulatory care setting or during well-woman visits. As well, concussion in women and men usually are not differentiated when considering presentation and adverse outcomes. Data are emerging that suggest concussion not only has long-term health implications but also that the effect of this injury in women compared with men is related to physical differences, cognitive differences (particularly in the verbal, quantitative, and visuospatial domains) and differences in the hormonal milieu. METHODS: A review of the literature on concussion in the female athlete on PubMed was conducted, with attention to both clinical studies and diagnostic studies. RESULTS: Data suggest that sex and gender contribute to concussion prevalence and severity, presenting symptoms, and recovery. For example, women may present with more drowsiness and sensitivity to noise after concussion than men. As well, increased surveillance appears to be warranted despite obvious behavioral recovery. Results of a longitudinal functional magnetic resonance imaging study in athletes with concussion suggest that neural recovery lags behind behaviorally assessed recovery, and alterations in white matter fiber tracts over the 2 months after injury have been demonstrated. Screening templates are available, and consideration of incorporation of relevant questionnaires into the electronic health record as well as the potential role of imaging will be discussed. CONCLUSION/IMPLICATION: Inquiry about concussion should be considered a part of the well-woman visit for all patients, especially those engaged in at-risk contact sports. The gynecologic visit and examination should include questions about head injury from sports involvement and a prior diagnosis of concussion.

Veins in plaques of multiple sclerosis patients – a longitudinal magnetic resonance imaging study at 7 Tesla –

To monitor the venous volumes in plaques of patients with multiple sclerosis (MS) compared to an age-matched control group over a period of 3.5 years. Ten MS patients underwent an annual neurological examination and MRI. Susceptibility-weighted imaging (SWI) combined with fluid-attenuated inversion recovery (FLAIR) or FLAIR-like contrast at 7 Tesla (7 T) magnetic resonance imaging (MRI) was used for manual segmentation of veins in plaques, in the normal-appearing white matter (NAWM) and in location-matched white matter of 9 age-matched controls. Venous volume to tissue volume ratio was assessed for each time point in order to describe the dynamics of venous volumes in MS plaques over time. MS plaques, which were newly detected during the study period, showed significantly higher venous volumes compared to the preplaque area 1 year before plaque detection and the corresponding NAWM regions. Venous volumes in established MS plaques, which were present already in the first scans, were significantly higher compared to the NAWM and controls. Our data underpin a relation of veins and plaque development in MS and reflect increased apparent venous calibers due to increased venous diameters or increased oxygen consumption in early MS plaques. • Longitudinal 7 T Magnetic Resonance Imaging study of intralesional veins in MS patients. • Venous volumes are significantly increased in newly detected and established MS plaques. • Venous volumes in established MS plaques show a trend to decrease with time.

Second language lexical development and cognitive control: A longitudinal fMRI study

In this paper we report a longitudinal functional magnetic resonance imaging (fMRI) study that tested contrasting predictions about the time course of cognitive control in second language (L2) acquisition. We examined the neural correlates of lexical processing in L2 learners twice over the course of one academic year. Specifically, while in the scanner, participants were asked to judge the language membership of unambiguous first and second language words, as well as interlingual homographs. Our ROI and connectivity analyses reveal that with increased exposure to the L2, overall activation in control areas such as the anterior cingulate cortex decrease while connectivity with semantic processing regions such as the middle temporal gyrus increase. These results suggest that cognitive control is more important initially in L2 acquisition, and have significant implications for understanding developmental and neurocognitive models of second language lexical processing.

Myocardial adaptation to high-intensity (interval) training in previously untrained men with a longitudinal cardiovascular magnetic resonance imaging study (Running Study and Heart Trial).

To prospectively evaluate whether short-term high-intensity (interval) training (HI(I)T) induces detectable morphological cardiac changes in previously untrained men in cardiovascular magnetic resonance imaging. Eighty-four untrained volunteers were randomly assigned to a HI(I)T group (n=42; 44.1±4.7 years) or an inactive control group (n=42; 42.3±5.6 years). HI(I)T focused on interval runs (intensity: 95%-105% of individually calculated heart rate at the anaerobic threshold). Before and after 16 weeks, all subjects underwent physiological examination, stepwise treadmill test with blood lactate analysis, and contrast-enhanced cardiovascular magnetic resonance imaging (cine, tagging, and delayed enhancement). Indexed left ventricular (LV) and right ventricular (RV) volume (LV, 77.1±8.5-83.9±8.6; RV, 80.5±8.5-86.6±8.1) and mass (LV, 58.2±6.4-63.4±8.1; RV, 14.8±1.7-16.1±2.1) significantly increased with HI(I)T. Changes in LV and RV morphological parameters with HI(I)T were highly correlated with an increase in maximal aerobic capacity (VO2max) and a decrease in blood lactate concentration at the anaerobic threshold. Mean LV and RV remodeling index of HI(I)T group did not alter with training (0.76 ±0.09 and 0.24±0.10 g/mL, respectively [P=0.97 and P=0.72]), indicating balanced cardiac adaptation. Myocardial circumferential strain decreased after HI(I)T within all 6 basal segments (anteroseptal, P=0.01 and anterolateral, P<0.001). There was no late gadolinium enhancement in any of the participants before or post HI(I)T. Sixteen weeks of HI(I)T lead to measurable changes in cardiac atrial and ventricular morphology and function in previously untrained men. This correlates with improvements in parameters of endurance capacity. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01406730.

Progressive Brain Atrophy and Cortical Thinning in Schizophrenia after Commencing Clozapine Treatment.

Despite evidence that clozapine may be neuroprotective, there are few longitudinal magnetic resonance imaging (MRI) studies that have specifically explored an association between commencement of clozapine treatment for schizophrenia and changes in regional brain volume or cortical thickness. A total of 33 patients with treatment-resistant schizophrenia and 31 healthy controls matched for age and gender underwent structural MRI brain scans at baseline and 6-9 months after commencing clozapine. MRI images were analyzed using SIENA (Structural Image Evaluation, using Normalization, of Atrophy) and FreeSurfer to investigate changes over time in brain volume and cortical thickness respectively. Significantly greater reductions in volume were detected in the right and left medial prefrontal cortex and in the periventricular area in the patient group regardless of treatment response. Widespread further cortical thinning was observed in patients compared with healthy controls. The majority of patients improved symptomatically and functionally over the study period, and patients who improved were more likely to have less cortical thinning of the left medial frontal cortex and the right middle temporal cortex. These findings demonstrate on-going reductions in brain volume and progressive cortical thinning in patients with schizophrenia who are switched to clozapine treatment. It is possible that this gray matter loss reflects a progressive disease process irrespective of medication use or that it is contributed to by switching to clozapine treatment. The clinical improvement of most patients indicates that antipsychotic-related gray matter volume loss may not necessarily be harmful or reflect neurotoxicity.

The effect of estrogen synthesis inhibition on hippocampal memory

17-Beta-estradiol (E2) facilitates long term-potentiation (LTP) and increases spine synapse density in hippocampal neurons of ovariectomized rodents. Consistent with these beneficial effects on the cellular level, E2 improves hippocampus-dependent memory. A prominent approach to study E2 effects in rodents is the inhibition of its synthesis by letrozole, which reduces LTPs and spine synapse density. In the current longitudinal functional magnetic resonance imaging (fMRI) study, we translated this approach to humans and compared the impact of E2 synthesis inhibition on memory performance and hippocampal activity in post-menopausal women taking letrozole (n = 21) to controls (n = 24). In particular, we employed various behavioral memory paradigms that allow the disentanglement of hippocampus-dependent and -independent memory. Consistent with the literature on rodents, E2 synthesis inhibition specifically impaired hippocampus-dependent memory, however, this did not apply to the same degree to all of the employed paradigms. On the neuronal level, E2 depletion tended to decrease hippocampal activity during encoding, whereas it increased activity in the anterior cingulate and the dorsolateral prefrontal cortex. We thus infer that the inhibition of E2 synthesis specifically impairs hippocampal functioning in humans, whereas the increased prefrontal activity presumably reflects a compensatory mechanism, which is already known from studies on cognitive aging and Alzheimer's disease.

Structural Brain Changes in First Episode Psychosis – a Longitudinal Mri Study

Background First-episode psychosis (FEP) patients show structural brain abnormalities. Whether the changes are progressive or not remain under debate, and the results from longitudinal magnetic resonance imaging (MRI) studies are mixed. We investigated if FEP patients showed a different pattern of regional brain structural change over a one-year period compared to healthy controls, and if putative changes correlated with clinical characteristics and outcome. Methods MRIs of 79 FEP (SCID-I verified diagnoses: schizophrenia, psychotic bipolar disorder, or other psychoses, mean age 27.6 (SD 7.7), 66% male) and 82 healthy controls (age 29.3 (SD 7.2) 66% male) were acquired from the same 1.5T scanner at baseline and one-year follow up as part of the TOP study, Oslo, Norway. Scans were automatically processed with the longitudinal stream in FreeSurfer. General linear models were used to analyze longitudinal change in a wide range of subcortical volumes and detailed thickness and surface area estimates across the entire cortex, and associations to clinical characteristics. Results FEP and controls did not differ significantly in annual percentage change in cortical thickness or area in any cortical region, or in any of the subcortical structures after adjustment for multiple comparisons. Within the FEP group, duration of untreated psychosis, age at illness onset, antipsychotic medication use, and remission at follow-up were not related to longitudinal brain change. Conclusion We found no longitudinal brain changes over a one-year period in FEP compared to controls. Our results do not support early progressive brain changes in psychotic disorders.