Accurate autocorrelation modeling substantially improves fMRI reliability.

Given the recent controversies in some neuroimaging statistical methods, we compare the most frequently used functional Magnetic Resonance Imaging (fMRI) analysis packages: AFNI, FSL and SPM, with regard to temporal autocorrelation modeling. This process, sometimes known as pre-whitening, is conducted in virtually all task fMRI studies. Here, we employ eleven datasets containing 980 scans corresponding to different fMRI protocols and subject populations. We found that autocorrelation modeling in AFNI, although imperfect, performed much better than the autocorrelation modeling of FSL and SPM. The presence of residual autocorrelated noise in FSL and SPM leads to heavily confounded first level results, particularly for low-frequency experimental designs. SPM's alternative pre-whitening method, FAST, performed better than SPM's default. The reliability of task fMRI studies could be improved with more accurate autocorrelation modeling. We recommend that fMRI analysis packages provide diagnostic plots to make users aware of any pre-whitening problems

Neuroimaging correlates of cognitive impairment and dementia in Parkinson's disease.

There has been a gradual shift in the definition of Parkinson's disease, from a movement disorder to a neurodegenerative condition affecting multiple cognitive domains. Mild cognitive impairment (PD-MCI) is a frequent comorbidity in PD that is associated with progression to dementia (PDD) and debilitating consequences for patients and caregivers. At present, the pathophysiology underpinning cognitive impairment in PD is not established, although emerging evidence has suggested that multi-modal imaging biomarkers could be useful in the early diagnosis of PD-MCI and PDD, thereby identifying at-risk patients to enable treatment at the earliest stage possible. Structural MRI studies have revealed prominent grey matter atrophy and disruptions of white matter tracts in PDD, although findings in non-demented PD have been more variable. There is a need for further longitudinal studies to clarify the spatial and temporal progression of morphological changes in PD, as well as to assess their underlying involvement in the evolution of cognitive deficits. In this review, we discuss the aetiology and neuropsychological profiles of PD-MCI and PDD, summarize the putative imaging substrates in light of evidence from multi-modal neuroimaging studies, highlight limitations in the present literature, and suggest recommendations for future research.This work was supported by the NIHR Biomedical Research Unit in Dementia and the Biomedical Research Centre awarded to Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge, and the NIHR Biomedical Research Unit in Dementia and the Biomedical Research Centre awarded to Newcastle upon Tyne Hospitals NHS Foundation Trust and the Newcastle University. Elijah Mak was in receipt of a Gates Cambridge PhD studentship.This is the accepted manuscript. The final version is available at http://www.sciencedirect.com/science/article/pii/S1353802015002151

A survey of patient motion in disorders of consciousness and optimization of its retrospective correction.

Functional magnetic resonance imaging (fMRI) can be seriously impaired by patient motion. The purpose of this study was to characterize the typical motion in a clinical population of patients in disorders of consciousness and compare the performance of retrospective correction with rigid-body realignment as implemented in widely used software packages. 63 subjects were scanned with an fMRI visual checkerboard paradigm using a 3T scanner. Time series were corrected for motion, and the resulting transformations were used to calculate a motion score. SPM, FSL, AFNI and AIR were evaluated by comparing the motion obtained by re-running the tool on the corrected data. A publicly available sample fMRI dataset was modified with the motion detected in each patient with each tool. The performance of each tool was measured by comparing the number of supra-threshold voxels after standard fMRI analysis, both in the sample dataset and in simulated fMRI data. We assessed the effect of user-changeable parameters on motion correction in SPM. We found the equivalent motion in the patient population to be 1.4mm on average. There was no significant difference in performance between SPM, FSL and AFNI. AIR was considerably worse, and took more time to run. We found that in SPM the quality factor and interpolation method have no effect on the cluster size, while higher separation and smoothing reduce it. We showed that the main packages SPM, FSL and AFNI are equally suitable for retrospective motion correction of fMRI time series. We show that typically only 80% of activated voxels are recovered by retrospective motion correction

Additional sampling directions improve detection range of wireless probes

PURPOSE: While MRI is enhancing our knowledge about the structure and function of the human brain, subject motion remains a problem in many clinical applications. Recently, the use of wireless radiofrequency markers with three one-dimensional (1D) navigators for prospective correction was demonstrated. This method is restricted in the range of motion that can be corrected, however, because of limited information in the 1D readouts. METHODS: Here, the limitation of techniques for disambiguating marker locations was investigated. It was shown that including more sampling directions extends the tracking range for head rotations. The efficiency of trading readout resolution for speed was explored. RESULTS: Tracking of head rotations was demonstrated from -19.2 to 34.4°, -2.7 to 10.0°, and -60.9 to 70.9° in the x-, y-, and z-directions, respectively. In the presence of excessive head motion, the deviation of marker estimates from SPM8 was reduced by 17.1% over existing three-projection methods. This was achieved by using an additional seven directions, extending the time needed for readouts by a factor of 3.3. Much of this increase may be circumvented by reducing resolution, without compromising accuracy. CONCLUSION: Including additional sampling directions extends the range in which markers can be used, for patients who move a lot. Magn Reson Med 76:913-918, 2016. © 2015 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.The project was supported by funding from the Isaac Newton Trust, the Wellcome Trust ISSF, and the Cusanuswerk funding body (Bonn, Germany).This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1002/mrm.2599

P-31 magnetization transfer measurements of P-i -> ATP flux in exercising human muscle

Fundamental criticisms have been made over the use of (31)P magnetic resonance spectroscopy (MRS) magnetization transfer estimates of inorganic phosphate (P(i))→ATP flux (V(Pi-ATP)) in human resting skeletal muscle for assessing mitochondrial function. Although the discrepancy in the magnitude of V(Pi-ATP) is now acknowledged, little is known about its metabolic determinants. Here we use a novel protocol to measure V(Pi-ATP) in human exercising muscle for the first time. Steady-state V(Pi-ATP) was measured at rest and over a range of exercise intensities and compared with suprabasal oxidative ATP synthesis rates estimated from the initial rates of postexercise phosphocreatine resynthesis (V(ATP)). We define a surplus P(i)→ATP flux as the difference between V(Pi-ATP) and V(ATP). The coupled reactions catalyzed by the glycolytic enzymes GAPDH and phosphoglycerate kinase (PGK) have been shown to catalyze measurable exchange between ATP and P(i) in some systems and have been suggested to be responsible for this surplus flux. Surplus V(Pi-ATP) did not change between rest and exercise, even though the concentrations of P(i) and ADP, which are substrates for GAPDH and PGK, respectively, increased as expected. However, involvement of these enzymes is suggested by correlations between absolute and surplus P(i)→ATP flux, both at rest and during exercise, and the intensity of the phosphomonoester peak in the (31)P NMR spectrum. This peak includes contributions from sugar phosphates in the glycolytic pathway, and changes in its intensity may indicate changes in downstream glycolytic intermediates, including 3-phosphoglycerate, which has been shown to influence the exchange between ATP and P(i) catalyzed by GAPDH and PGK

Longitudinal assessment of global and regional atrophy rates in Alzheimer's disease and dementia with Lewy bodies.

BACKGROUND & OBJECTIVE: Percent whole brain volume change (PBVC) measured from serial MRI scans is widely accepted as a sensitive marker of disease progression in Alzheimer's disease (AD). However, the utility of PBVC in the differential diagnosis of dementia remains to be established. We compared PBVC in AD and dementia with Lewy bodies (DLB), and investigated associations with clinical measures. METHODS: 72 participants (14 DLBs, 25 ADs, and 33 healthy controls (HCs)) underwent clinical assessment and 3 Tesla T1-weighted MRI at baseline and repeated at 12 months. We used FSL-SIENA to estimate PBVC for each subject. Voxelwise analyses and ANCOVA compared PBVC between DLB and AD, while correlational tests examined associations of PBVC with clinical measures. RESULTS: AD had significantly greater atrophy over 1 year (1.8%) compared to DLB (1.0%; p = 0.01) and HC (0.9%; p < 0.01) in widespread regions of the brain including periventricular areas. PBVC was not significantly different between DLB and HC (p = 0.95). There were no differences in cognitive decline between DLB and AD. In the combined dementia group (AD and DLB), younger age was associated with higher atrophy rates (r = 0.49, p < 0.01). CONCLUSIONS: AD showed a faster rate of global brain atrophy compared to DLB, which had similar rates of atrophy to HC. Among dementia subjects, younger age was associated with accelerated atrophy, reflecting more aggressive disease in younger people. PBVC could aid in differentiating between DLB and AD, however its utility as an outcome marker in DLB is limited.This work was supported by the Sir Jules Thorn Charitable Trust (grant number 05/JTA), the NIHR Biomedical Research Unit in Dementia and the Biomedical Research Centre awarded to Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge, and the NIHR Biomedical Research Unit in Dementia and the Biomedical Research Centre awarded to Newcastle upon Tyne Hospitals NHS Foundation Trust and the Newcastle University. Elijah Mak was in receipt of a Gates Cambridge, PhD studentship.This is the final published version. It first appeared at http://www.sciencedirect.com/science/article/pii/S2213158215000182#

The Value of Sex in Procreative Reasons

Copyright Taylor and Francis Group, LLC. This is an open access article distributed under the Supplemental Terms and Conditions for iOpenAccess articles published in Taylor & Francis journals, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Progressive cortical thinning and subcortical atrophy in dementia with Lewy bodies and Alzheimer's disease.

Patterns of progressive cortical thinning in dementia with Lewy bodies (DLB) remain poorly understood. We examined spatiotemporal patterns of cortical thinning and subcortical atrophy over 12 months in DLB (n = 13), compared with Alzheimer's disease (AD) (n = 23) and healthy control subjects (HC) (n = 33). Rates of temporal thinning in DLB were relatively preserved compared with AD. Volumetric analyses subcortical changes revealed that the AD group demonstrated significantly increased hippocampal atrophy (-5.8%) relative to the HC (-1.7%; p < 0.001) and DLB groups (-2.5%, p = 0.006). Significant lateral ventricular expansion was also observed in AD (8.9%) compared with HC (4.3%; p < 0.001) and DLB (4.7%; p = 0.008) at trend level. There was no significant difference in subcortical atrophy and ventricular expansion between DLB and HC. In the DLB group, increased rates of cortical thinning in the frontal and parietal regions were significantly correlated with decline in global cognition (Mini-Mental State Examination) and motor deterioration (Unified Parkinson's Disease Rating Scale 3), respectively. Overall, AD and DLB are characterized by different spatiotemporal patterns of cortical thinning over time. Our findings warrant further consideration of longitudinal cortical thinning as a potential imaging marker to differentiate DLB from AD.This work was supported by the Sir Jules Thorn Charitable Trust (Grant number 05/JTA), the NIHR Biomedical Research Unit in Dementia and the Biomedical Research Centre awarded to Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge, and the NIHR Biomedical Research Unit in Dementia and the Biomedical Research Centre awarded to Newcastle upon Tyne Hospitals NHS Foundation Trust and the Newcastle University. Elijah Mak was in receipt of a Gates Cambridge PhD studentship. Elijah Mak formulated the research question, performed the statistical analyses, interpreted the results, and wrote the article. Li Su and Guy Williams assisted with the interpretation of the results and provided comments and additional suggestions for revisions of the draft. Rosie Watson recruited and assessed study participants, assisted with the interpretation of the results, and reviewed the article. Michael Firbank designed the imaging protocol, assisted with the interpretation of the results, and reviewed the article. Andrew Blamire obtained funding for the project, designed the imaging protocol, undertook routine quality assurance on the MR system, assisted with the interpretation of the results, and reviewed the article. John O’Brien obtained funding for the project, designed the imaging protocol, assisted with recruitment of study participants, assisted with the interpretation of the results, and reviewed the article. All authors approved the final article.This is the accepted manuscript for a paper published in Neurobiology of Aging Volume 36, Issue 4, April 2015, Pages 1743–1750, DOI: 10.1016/j.neurobiolaging.2014.12.03

Distinctive Personality Traits and Neural Correlates Associated with Stimulant Drug Use Versus Familial Risk of Stimulant Dependence

BackgroundStimulant drugs such as cocaine and amphetamine have a high abuse liability, but not everyone who uses them develops dependence. However, the risk for dependence is increased for individuals with a family history of addiction. We hypothesized that individuals without a family history of dependence who have been using cocaine recreationally for several years but have not made the transition to dependence will differ in terms of personality traits and brain structure from individuals who are either dependent on stimulants or at risk for dependence.MethodsWe compared 27 individuals without a familial risk of dependence who had been using cocaine recreationally with 50 adults with stimulant dependence, their nondependent siblings (n = 50), and unrelated healthy volunteers (n = 52) who had neither a personal nor a family history of dependence. All participants underwent a magnetic resonance imaging brain scan and completed a selection of personality measures that have been associated with substance abuse.ResultsIncreased sensation-seeking traits and abnormal orbitofrontal and parahippocampal volume were shared by individuals who were dependent on stimulant drugs or used cocaine recreationally. By contrast, increased levels of impulsive and compulsive personality traits and limbic-striatal enlargement were shared by stimulant-dependent individuals and their unaffected siblings.ConclusionsWe provide evidence for distinct neurobiological phenotypes that are either associated with familial vulnerability for dependence or with regular stimulant drug use. Our findings further suggest that some individuals with high sensation-seeking traits but no familial vulnerability for dependence are likely to use cocaine but may have relatively low risk for developing dependence

Brain networks underlying vulnerability and resilience to drug addiction.

Regular drug use can lead to addiction, but not everyone who takes drugs makes this transition. How exactly drugs of abuse interact with individual vulnerability is not fully understood, nor is it clear how individuals defy the risks associated with drugs or addiction vulnerability. We used resting-state functional MRI (fMRI) in 162 participants to characterize risk- and resilience-related changes in corticostriatal functional circuits in individuals exposed to stimulant drugs both with and without clinically diagnosed drug addiction, siblings of addicted individuals, and control volunteers. The likelihood of developing addiction, whether due to familial vulnerability or drug use, was associated with significant hypoconnectivity in orbitofrontal and ventromedial prefrontal cortical-striatal circuits-pathways critically implicated in goal-directed decision-making. By contrast, resilience against a diagnosis of substance use disorder was associated with hyperconnectivity in two networks involving 1) the lateral prefrontal cortex and medial caudate nucleus and 2) the supplementary motor area, superior medial frontal cortex, and putamen-brain circuits respectively implicated in top-down inhibitory control and the regulation of habits. These findings point toward a predisposing vulnerability in the causation of addiction, related to impaired goal-directed actions, as well as countervailing resilience systems implicated in behavioral regulation, and may inform novel strategies for therapeutic and preventative interventions.This research was funded by a Medical Research Council (MRC) grant (G0701497), financially supported by the NIHR Cambridge Biomedical Research Centre, and conducted within the Behavioural and Clinical Neuroscience Institute (BCNI). CM was supported by the Wellcome Trust grant to KDE (105602/Z/14/Z) and the NIHR Cambridge Biomedical Research Centre. JS was partly supported by the NIHR CLAHRC East of England and by the Charles University PRVOUK programme P38. TWR is a recipient of a Wellcome Trust Senior Investigator Award (104631/z/14/z). TWR discloses consultancy with Cambridge Cognition, Greenfield Bioventures and Unilever; he receives royalties for CANTAB from Cambridge Cognition, research grants from Shionogi and GlaxoSmithKline and editorial honoraria from Springer Verlag and Elsevier. ETB is a National Institute for Health Research Senior Investigator