Interactive Effects of Physical Activity and APOE-ε4 On White Matter Tract Diffusivity in Healthy Elders

Older adult apolipoprotein-E epsilon 4 (APOE-ε4) allele carriers vary considerably in the expression of clinical symptoms of Alzheimer\u27s disease (AD), suggesting that lifestyle or other factors may offer protection from AD-related neurodegeneration. We recently reported that physically active APOE-ε4 allele carriers exhibit a stable cognitive trajectory and protection from hippocampal atrophy over 18 months compared to sedentary ε4 allele carriers. The aim of this study was to examine the interactions between genetic risk for AD and physical activity (PA) on white matter (WM) tract integrity, using diffusion tensor imaging (DTI) MRI, in this cohort of healthy older adults (ages of 65 to 89). Four groups were compared based on the presence or absence of an APOE-ε4 allele (High Risk; Low Risk) and self-reported frequency and intensity of leisure time physical activity (PA) (High PA; Low PA). As predicted, greater levels of PA were associated with greater fractional anisotropy (FA) and lower radial diffusivity in healthy older adults who did not possess the APOE-ε4 allele. However, the effects of PA were reversed in older adults who were at increased genetic risk for AD, resulting in significant interactions between PA and genetic risk in several WM tracts. In the High Risk-Low PA participants, who had exhibited episodic memory decline over the previous 18-months, radial diffusivity was lower and fractional anisotropy was higher, compared to the High Risk-High PA participants. In WM tracts that subserve learning and memory processes, radial diffusivity (DR) was negatively correlated with episodic memory performance in physically inactive APOE-ε4 carriers, whereas DR was positively correlated with episodic memory performance in physically active APOE-ε4 carriers and the two Low Risk groups. The common model of demyelination-induced increase in radial diffusivity cannot directly explain these results. Rather, we hypothesize that PA may protect APOE-ε4 allele carriers from selective neurodegeneration of individual fiber populations at locations of crossing fibers within projection and association WM fiber tracts

Intrinsic Frontolimbic Connectivity and Mood Symptoms in Young Adult Cannabis Users.

Objective: The endocannbinoid system and cannabis exposure has been implicated in emotional processing. The current study examined whether regular cannabis users demonstrated abnormal intrinsic (a.k.a. resting state) frontolimbic connectivity compared to non-users. A secondary aim examined the relationship between cannabis group connectivity differences and self-reported mood and affect symptoms. Method: Participants included 79 cannabis-using and 80 non-using control emerging adults (ages of 18-30), balanced for gender, reading ability, and age. Standard multiple regressions were used to predict if cannabis group status was associated with frontolimbic connectivity after controlling for site, past month alcohol and nicotine use, and days of abstinence from cannabis. Results: After controlling for research site, past month alcohol and nicotine use, and days of abstinence from cannabis, cannabis users demonstrated significantly greater connectivity between left rACC and the following: right rACC (p = 0.001; corrected p = 0.05; f 2 = 0.55), left amygdala (p = 0.03; corrected p = 0.47; f 2 = 0.17), and left insula (p = 0.03; corrected p = 0.47; f 2 = 0.16). Among cannabis users, greater bilateral rACC connectivity was significantly associated with greater subthreshold depressive symptoms (p = 0.02). Conclusions: Cannabis using young adults demonstrated greater connectivity within frontolimbic regions compared to controls. In cannabis users, greater bilateral rACC intrinsic connectivity was associated with greater levels of subthreshold depression symptoms. Current findings suggest that regular cannabis use during adolescence is associated with abnormal frontolimbic connectivity, especially in cognitive control and emotion regulation regions

fMRI of Healthy Older Adults During Stroop Interference

The Stroop interference effect, caused by difficulty inhibiting overlearned word reading, is often more pronounced in older adults. This has been proposed to be due to declines in inhibitory control and frontal lobe functions with aging. Initial neuroimaging studies of inhibitory control show that older adults have enhanced activation in multiple frontal areas, particularly in inferior frontal gyrus, indicative of recruitment to aid with performance of the task. The current study compared 13 younger and 13 older adults, all healthy and well educated, who completed a Stroop test during functional magnetic resonance imaging. Younger adults were more accurate across conditions, and both groups were slower and less accurate during the interference condition. The groups exhibited comparable activation regions, but older adults exhibited greater activation in numerous frontal areas, including the left inferior frontal gyrus. The results support the recruitment construct and suggest, along with previous research, that the inferior frontal gyrus is important for successful inhibition

Improving language mapping in clinical fMRI through assessment of grammar.

IntroductionBrain surgery in the language dominant hemisphere remains challenging due to unintended post-surgical language deficits, despite using pre-surgical functional magnetic resonance (fMRI) and intraoperative cortical stimulation. Moreover, patients are often recommended not to undergo surgery if the accompanying risk to language appears to be too high. While standard fMRI language mapping protocols may have relatively good predictive value at the group level, they remain sub-optimal on an individual level. The standard tests used typically assess lexico-semantic aspects of language, and they do not accurately reflect the complexity of language either in comprehension or production at the sentence level. Among patients who had left hemisphere language dominance we assessed which tests are best at activating language areas in the brain.MethodWe compared grammar tests (items testing word order in actives and passives, wh-subject and object questions, relativized subject and object clauses and past tense marking) with standard tests (object naming, auditory and visual responsive naming), using pre-operative fMRI. Twenty-five surgical candidates (13 females) participated in this study. Sixteen patients presented with a brain tumor, and nine with epilepsy. All participants underwent two pre-operative fMRI protocols: one including CYCLE-N grammar tests (items testing word order in actives and passives, wh-subject and object questions, relativized subject and object clauses and past tense marking); and a second one with standard fMRI tests (object naming, auditory and visual responsive naming). fMRI activations during performance in both protocols were compared at the group level, as well as in individual candidates.ResultsThe grammar tests generated more volume of activation in the left hemisphere (left/right angular gyrus, right anterior/posterior superior temporal gyrus) and identified additional language regions not shown by the standard tests (e.g., left anterior/posterior supramarginal gyrus). The standard tests produced more activation in left BA 47. Ten participants had more robust activations in the left hemisphere in the grammar tests and two in the standard tests. The grammar tests also elicited substantial activations in the right hemisphere and thus turned out to be superior at identifying both right and left hemisphere contribution to language processing.ConclusionThe grammar tests may be an important addition to the standard pre-operative fMRI testing

Hand classification of fMRI ICA noise components

We present a practical "how-to" guide to help determine whether single-subject fMRI independent components (ICs) characterise structured noise or not. Manual identification of signal and noise after ICA decomposition is required for efficient data denoising: to train supervised algorithms, to check the results of unsupervised ones or to manually clean the data. In this paper we describe the main spatial and temporal features of ICs and provide general guidelines on how to evaluate these. Examples of signal and noise components are provided from a wide range of datasets (3T data, including examples from the UK Biobank and the Human Connectome Project, and 7T data), together with practical guidelines for their identification. Finally, we discuss how the data quality, data type and preprocessing can influence the characteristics of the ICs and present examples of particularly challenging datasets

Neural indicators of fatigue in chronic diseases : A systematic review of MRI studies

The authors would like to thank the Sir Jules Thorn Charitable Trust for their financial support.Peer reviewedPublisher PD

Gray matter structural correlates of fatigue in multiple sclerosis

We aimed to assess whether frontal cortex-striatum-thalamus (FCST) pathway or other grey matter (GM) structures are associated with longitudinal patterns of fatigue, namely reversible (RF) versus sustained fatigue (SF). MS patients enrolled in our prospective cohort were grouped based on their longitudinal Modified Fatigue Impact Scale (MFIS) scores: 1. SF: MFIS≥38 at the two most recent yearly assessments; 2. RF: MFIS<38 at last assessment, but presence of at least one previous MFIS≥38; 3. Never Fatigued (NF): at least five MFIS<38. Accordingly, we selected 98 patients (30 SF, 31 RF, 37 NF; age-range:29-66, female/male:76/22, Extended Disability Status Scale (EDSS)6; 13 patients with secondary progressive (SP) MS and 85 with relapsing remitting (RR) MS in remission). Disability and depression were assessed using the EDSS and CES-D, respectively. 3T T1-weighted MRI was used for voxel based morphometry (VBM) to survey for GM atrophy associated with fatigue, controlling for age, sex and EDSS. Group-wise volumetric comparison was performed on deep GM structures identified by VBM, controlling for age, sex, EDSS and CES-D score. VBM showed significant inverse relation between the MFIS cognitive subscale score and areas within the bilateral fronto-medial and fronto-orbital cortices, anterior striata, thalami, temporal poles, insulae and left lateral occipital cortex (peak FWE-p value of 0.021), and between the MFIS physical subscale and areas within the bilateral frontal poles, and frontal medial cortices (peak FWE-p value of 0.043). Volumetric analysis showed significant atrophy in the putamen (RF<NF p<0.0004; SF<NF p<0.0085) and thalamus (RF<NF p<0.00048)

Quantitative Susceptibility Mapping: Contrast Mechanisms and Clinical Applications.

Quantitative susceptibility mapping (QSM) is a recently developed MRI technique for quantifying the spatial distribution of magnetic susceptibility within biological tissues. It first uses the frequency shift in the MRI signal to map the magnetic field profile within the tissue. The resulting field map is then used to determine the spatial distribution of the underlying magnetic susceptibility by solving an inverse problem. The solution is achieved by deconvolving the field map with a dipole field, under the assumption that the magnetic field is a result of the superposition of the dipole fields generated by all voxels and that each voxel has its unique magnetic susceptibility. QSM provides improved contrast to noise ratio for certain tissues and structures compared to its magnitude counterpart. More importantly, magnetic susceptibility is a direct reflection of the molecular composition and cellular architecture of the tissue. Consequently, by quantifying magnetic susceptibility, QSM is becoming a quantitative imaging approach for characterizing normal and pathological tissue properties. This article reviews the mechanism generating susceptibility contrast within tissues and some associated applications