Neural correlates of the revised reinforcement sensitivity theory: A cross-sectional structural neuroimaging study in middle-aged adults.

The revised reinforcement sensitivity theory (RST) proposes that neurobiological systems control behavior: the fight-flight-freeze (FFFS) for avoidance of threat; behavioral approach/activation (BAS) for approach to rewards; and behavioral inhibition (BIS) for conflict resolution when avoidance and approach are possible. Neuroimaging studies have confirmed some theoretical associations between brain structures and the BAS and BIS; however, little representative population data are available for the FFFS. We investigated the neural correlates of the revised RST in a sample of 404 middle-aged adults (Mage = 47.18 (SD = 1.38); 54.5% female). Participants underwent structural magnetic resonance imaging and completed health questionnaires and the BIS/BAS/FFFS scales. We used multiple regression analyses to investigate the association between scale scores and volumes of a priori theoretically linked regions of interest while controlling for sex, age, intracranial volume, and cardio-metabolic variables; and conducted exploratory analyses on cortical thickness. The BIS was negatively associated with hippocampus laterality. At standard significance levels, the fear component of the FFFS was positively associated with anterior cingulate cortex; the BAS was positively associated with bilateral caudate; and the BIS was positively associated with posterior cingulate cortex volume. Furthermore, these neurobiological systems showed distinct patterns of association with cortical thickness though future work is needed. Our results showed that the neurobiological systems of the revised RST characterized in rodents can also be identified in the human brain.

Longitudinal Effects of Physical Activity Change on Hippocampal Volumes over up to 12 Years in Middle and Older Age Community-Dwelling Individuals.

The objectives of this study were to investigate the long-term associations between changes in physical activity levels and hippocampal volumes over time, while considering the influence of age, sex, and APOE-ε4 genotype. We investigated the effects of change in physical activity on hippocampal volumes in 411 middle age (mean age = 47.2 years) and 375 older age (mean age = 63.1 years) adults followed up to 12 years. An annual volume decrease was observed in the left (middle age: 0.46%; older age: 0.51%) but not in the right hippocampus. Each additional 10 metabolic equivalents (METs, ~2 h of moderate exercise) increase in weekly physical activity was associated with 0.33% larger hippocampal volume in middle age (equivalent to ~1 year of typical aging). In older age, each additional MET was associated with 0.05% larger hippocampal volume; however, the effects declined with time by 0.005% per year. For older age APOE-ε4 carriers, each additional MET was associated with a 0.10% increase in hippocampal volume. No sex effects of physical activity change were found. Increasing physical activity has long-term positive effects on hippocampal volumes and appears especially beneficial for older APOE-ε4 carriers. To optimize healthy brain aging, physical activity programs should focus on creating long-term exercise habits.

Midsagittal corpus callosal thickness and cognitive impairment in Parkinson's disease.

People diagnosed with Parkinson's disease (PD) can experience significant neuropsychiatric symptoms, including cognitive impairment and dementia, the neuroanatomical substrates of which are not fully characterised. Symptoms associated with cognitive impairment and dementia in PD may relate to direct structural changes to the corpus callosum via primary white matter pathology or as a secondary outcome due to the degeneration of cortical regions. Using magnetic resonance imaging, the corpus callosum can be investigated at the midsagittal plane, where it converges to a contiguous mass and is not intertwined with other tracts. The objective of this project was thus twofold: First, we investigated possible changes in the thickness of the midsagittal callosum and cortex in patients with PD with varying levels of cognitive impairment; and secondly, we investigated the relationship between the thickness of the midsagittal corpus callosum and the thickness of the cortex. Study participants included cognitively unimpaired PD participants (n = 35), PD participants with mild cognitive impairment (n = 22), PD participants with dementia (n = 17) and healthy controls (n = 27). We found thinning of the callosum in PD-related dementia compared with PD-related mild cognitive impairment and cognitively unimpaired PD participants. Regression analyses found thickness of the left medial orbitofrontal cortex to be positively correlated with thickness of the anterior callosum in PD-related mild cognitive impairment. This study suggests that a midsagittal thickness model can uncover changes to the corpus callosum in PD-related dementia, which occur in line with changes to the cortex in this advanced disease stage.

Objectively measured physical activity is associated with dorsolateral prefrontal cortex volume in older adults.

BACKGROUND: Epidemiological studies suggest physical activity (PA) can slow or prevent both cognitive decline and age-related atrophy in frontal and hippocampal gray matter volumes. However, much of this evidence is based on self-reported measures of PA. METHODS: PA was measured objectively with a SenseWear™ Armband to examine the cross-sectional associations between the duration of light, moderate and vigorous intensity PA with gray matter volume in the dorsolateral prefrontal cortex (DLPFC) and hippocampus in 167 (female: 43%) cognitively healthy older adults aged 73 to 78. RESULTS: The duration of objective moderate to vigorous intensity physical activity (MVPA) was associated with a greater volume of the right DLPFC (ߠ​= â€‹0.16; p â€‹= â€‹0.04). In addition, objective moderate-intensity PA alone was also associated with greater volume of the left (ߠ​= â€‹0.17; p â€‹= â€‹0.03) and right (ߠ​= â€‹0.19; p â€‹= â€‹0.01) DLPFC after controlling for covariates and adjustment for multiple comparisons. In contrast, there were no significant associations between light- or vigorous-intensity PA and gray matter volumes (all p â€‹> â€‹0.05). No associations between PA and cognitive performance were detected, and self-reported PA was not associated with any of the outcomes investigated. CONCLUSIONS: These findings suggest that an intensity-dependent relationship may exist, whereby a greater duration of MVPA, perhaps driven by moderate-intensity PA, is associated with preserved gray matter volume in frontal regions of the brain. Future research should investigate the mechanisms of this dose-effect and determine whether greater brain volumes associated with objective PA convey protective effects against cognitive decline.

Volumetric brain differences in clinical depression in association with anxiety: a systematic review with meta-analysis.

Background: Structural differences associated with depression have not been confirmed in brain regions apart from the hippocampus. Comorbid anxiety has been inconsistently assessed, and may explain discrepancies in previous findings. We investigated the link between depression, comorbid anxiety and brain structure. Methods: We followed Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines (PROSPERO CRD42018089286). We searched the Cochrane Library, MEDLINE, PsycInfo, PubMed and Scopus, from database inception to Sept. 13, 2018, for MRI case-control studies that reported brain volumes in healthy adults and adults with clinical depression. We summarized mean volumetric differences using meta-analyses, and we assessed demographics, depression factors and segmentation procedure as moderators using meta-regressions. Results: We included 112 studies in the meta-analyses, assessing 4911 healthy participants and 5934 participants with depression (mean age 49.8 yr, 68.2% female). Volume effects were greater in late-onset depression and in multiple episodes of depression. Adults with depression and no comorbidity showed significantly lower volumes in the putamen, pallidum and thalamus, as well as significantly lower grey matter volume and intracranial volume; the largest effects were in the hippocampus (6.8%, p < 0.001). Adults with depression and comorbid anxiety showed significantly higher volumes in the amygdala (3.6%, p < 0.001). Comorbid anxiety lowered depression effects by 3% on average. Sex moderated reductions in intracranial volume. Limitations: High heterogeneity in hippocampus effects could not be accounted for by any moderator. Data on symptom severity and medication were sparse, but other factors likely made significant contributions. Conclusion: Depression-related differences in brain structure were modulated by comorbid anxiety, chronicity of symptoms and onset of illness. Early diagnosis of anxiety symptomatology will prove crucial to ensuring effective, tailored treatments for improving long-term mental health and mitigating cognitive problems, given the effects in the hippocampus.

More highly myelinated white matter tracts are associated with faster processing speed in healthy adults.

The objective of this study was to investigate whether the estimated myelin content of white matter tracts is predictive of cognitive processing speed and whether such associations are modulated by age. Associations between estimated myelin content and processing speed were assessed in 570 community-living individuals (277 middle-age, 293 older-age). Myelin content was estimated in-vivo using the mean T1w/T2w magnetic resonance ratio, in six white matter tracts (anterior corona radiata, superior corona radiata, pontine crossing tract, anterior limb of the internal capsule, genu of the corpus callosum, and splenium of the corpus callosum). Processing speed was estimated by extracting a principal component from 5 separate tests of processing speed. It was found that estimated myelin content of the bilateral anterior limb of the internal capsule and left splenium of the corpus callosum were significant predictors of processing speed, even after controlling for socio-demographic, health and genetic variables and correcting for multiple comparisons. One SD higher in the estimated myelin content of the anterior limb of the internal capsule was associated with 2.53% faster processing speed and within the left splenium of the corpus callosum with 2.20% faster processing speed. In addition, significant differences in estimated myelin content between middle-age and older participants were found in all six white matter tracts. The present results indicate that myelin content, estimated in vivo using a neuroimaging approach in healthy older adults, is sufficiently precise to predict variability in processing speed in behavioural measures.

Longitudinal Assessment of Hippocampal Atrophy in Midlife and Early Old Age: Contrasting Manual Tracing and Semi-automated Segmentation (FreeSurfer).

It is important to have accurate estimates of normal age-related brain structure changes and to understand how the choice of measurement technique may bias those estimates. We compared longitudinal change in hippocampal volume, laterality and atrophy measured by manual tracing and FreeSurfer (version 5.3) in middle age (n = 244, 47.2[1.4] years) and older age (n = 199, 67.0[1.4] years) individuals over 8 years. The proportion of overlap (Dice coefficient) between the segmented hippocampi was calculated and we hypothesised that the proportion of overlap would be higher for older individuals as a consequence of higher atrophy. Hippocampal volumes produced by FreeSurfer were larger than manually traced volumes. Both methods produced a left less than right volume laterality difference. Over time this laterality difference increased for manual tracing and decreased for FreeSurfer leading to laterality differences in left and right estimated atrophy rates. The overlap proportion between methods was not significantly different for older individuals, but was greater for the right hippocampus. Estimated middle age annualised atrophy rates were - 0.39(1.0) left, 0.07(1.01) right, - 0.17(0.88) total for manual tracing and - 0.15(0.69) left, - 0.20(0.63) right, - 0.18(0.57) total for FreeSurfer. Older age atrophy rates were - 0.43(1.32) left, - 0.15(1.41) right, - 0.30 (1.23) total for manual tracing and - 0.34(0.79) left, - 0.68(0.78) right, - 0.51(0.65) total for FreeSurfer. FreeSurfer reliably segments the hippocampus producing atrophy rates that are comparable to manual tracing with some biases that need to be considered in study design. FreeSurfer is suited for use in large longitudinal studies where it is not cost effective to use manual tracing.

The cerebellum shrinks faster than normal ageing in Alzheimer's disease but not in mild cognitive impairment.

BACKGROUND: While acceleration in age-related cerebral atrophy has been well documented in Alzheimer's disease, the cerebellar contributions to this effect have not been thoroughly investigated. OBJECTIVE: This study investigated cerebellar volume and atrophy rate using magnetic resonance imaging in individuals with normal cognition (CN), mild cognitive impairment (MCI), and Alzheimer's disease (AD). METHODS: Two hundred twenty-nine CN, 398 MCI and 191 AD participants of stage I ADNI database with screening scans were evaluated for cerebellar volume. Of those, 758 individuals with two or more follow-up scans were categorized into stable, converted, and reverted CN, MCI and AD and evaluated for cerebellar atrophy rate. RESULTS: Cerebellar volume was 2.5% larger in CN than in those with AD but there were no differences between CN and MCI and MCI and AD in cross-sectional analysis. Similarly, the atrophy rate was 49% larger in AD and 64% larger in MCI who converted to AD but no difference was detected between CN and MCI. There were no association between education and APOEe4 and cerebellar volume or cerebellar atrophy across the diagnostic groups. CONCLUSION: Cerebellar atrophy contributes to Alzheimer's clinical progression but mostly at the late stage of the disease. However, even in the late stage shrinkage rate is less than the average of the shrinkage in the cerebrum and is not associated with AD moderators. This suggests that cerebellar involvement is secondary to cerebral involvement and can be due to network connection spread regardless of the primary pathology. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc. Hum Brain Mapp 38:3141-3150, 2017. © 2017 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. Hum Brain Mapp 38:3141-3150, 2017. © 2017 Wiley Periodicals, Inc.

Higher Fasting Plasma Glucose is Associated with Increased Cortical Thinning Over 12 Years: The PATH Through Life Study.

Recent evidence suggests that type 2 diabetes (T2D) is associated with accelerated brain ageing, consistent with the observation of increased risk of cognitive impairment and dementia in affected individuals. Even non-diabetic individuals with impaired fasting plasma glucose (IFG) levels have shown increased cerebral atrophy, compared to individuals with normal glucose levels. We tested whether longitudinal rates of age-related cortical thinning were associated with fasting plasma glucose levels in a large sample (n = 322) of early-old age individuals (60-66 years) who were scanned with magnetic resonance imaging (1.5 T) on up to four occasions over 12 years. Higher plasma glucose levels (measured on up to three occasions) were associated with increased cortical thinning in individuals with T2D as well as those with IFG, with a similar trend for individuals with normal fasting glucose (NFG) levels. Across groups, a 1 mmol/l increase in plasma glucose (above 5 mmol/l in NFG and IFG and above 6.1 mmol/l in T2D) resulted in a 10-13% increase in annual cortical thinning. Increased cortical thinning was detected in insular cortex, as well as posterior cingulate, parahippocampus and medial orbitofrontal cortex. Our results provide support for the idea that raised plasma glucose levels, even in the normal range, are associated with accelerated age-related cortical atrophy.

Cortical Thinning at Midlife: The PATH Through Life Study.

Cortical thinning is a part of normal ageing. Recent studies suggest that accelerated cortical thinning in vulnerable regions may be a useful biomarker for neuropathologies including Alzheimer's disease (AD). Longitudinal studies, which have largely focused on older adults, have provided estimates of normative rates and patterns of age-related cortical thinning. Very little, however, is known about healthy cortical thinning at midlife. Here we provide longitudinal estimates of age-related cortical thinning observed over 8 years, in a large (n = 404) group of healthy individuals aged 44-49 years at baseline, who were scanned with MRI (1.5T) on up to three occasions. Age-related cortical thinning was assessed across the whole cortex. We measured a mean annual decrease in cortical thickness of 0.26 % on the left and 0.17 % on the right hemisphere, and largely affecting frontal and cingulate cortices. Medial and lateral temporal regions were generally spared. Studying regions that are specifically vulnerable to-or spared from-healthy age-related cortical thinning at midlife may be important for the early identification of neurodegeneration, including AD.

A systematic review and meta-analysis of longitudinal hippocampal atrophy in healthy human ageing.

INTRODUCTION: This review aimed to produce hippocampal atrophy rate estimates from healthy ageing studies as well as control samples from observational studies across the adult lifespan which can be used as benchmarks to evaluate abnormal changes in pathological conditions. METHODS: The review followed PRISMA guidelines. PUBMED (to February 2014) was searched for longitudinal MRI studies reporting hippocampal atrophy or volume change in cognitively healthy individuals. Titles were screened and non-English, duplicate or irrelevant entries were excluded. Remaining record abstracts were reviewed to identify studies for full text retrieval. Full text was retrieved and screened against inclusion/exclusion criteria. Bibliographies and previous reviews were examined to identify additional studies. Data were summarised using meta-analysis and age, segmentation technique and study type were tested as potential moderators using meta-regression. It was hypothesised that population studies would produce higher atrophy rates than clinical observational studies. RESULTS: The systematic search identified 4410 entries and 119 studies were retrieved with 58 failing selection or quality criteria, 30 were excluded as multiple reports and 3 studies were unsuitable for meta-analysis. The remaining 28 studies were included in the meta-analysis, n=3422, 44.65% male, 11,735 person-years of follow-up, mean age was 24.50 to 83 years. Mean total hippocampal atrophy for the entire sample was 0.85% per year (95% CI 0.63, 1.07). Age based atrophy rates were 0.38% per year (CI 0.14, 0.62) for studies with mean age <55 years (n=413), 0.98% (CI 0.27, 1.70) for 55 to <70 years (n=426), and 1.12% (CI 0.86, 1.38) for ≥70 years (n=2583). Meta-regression indicated age was associated with increased atrophy rates of 0.0263% (CI 0.0146, 0.0379) per year and automated segmentation approaches were associated with a reduced atrophy rate of -0.466% (CI -0.841, -0.090). Population studies were not associated with a significant effect on atrophy. Analyses of 11 studies separately measuring left and right hippocampal atrophy (n=1142) provided little evidence of laterality effects. While no study separately reported atrophy by gender, a number tested for gender effects and 2 studies reported higher atrophy in males. CONCLUSIONS: Hippocampal atrophy rates increase with age with the largest increases occurring from midlife onwards. Manual segmentation approaches result in higher measured atrophy rates.

A role for retro-splenial cortex in the task-related P3 network.

OBJECTIVE: The P3 is an event-related response observed in relation to task-relevant sensory events. Despite its ubiquitous presence, the neural generators of the P3 are controversial and not well identified. METHODS: We compared source analysis of combined magneto- and electroencephalography (M/EEG) data with functional magnetic resonance imaging (fMRI) and simulation studies to better understand the sources of the P3 in an auditory oddball paradigm. RESULTS: Our results suggest that the dominant source of the classical, postero-central P3 lies in the retro-splenial cortex of the ventral cingulate gyrus. A second P3 source in the anterior insular cortex contributes little to the postero-central maximum. Multiple other sources in the auditory, somatosensory, and anterior midcingulate cortex are active in an overlapping time window but can be functionally dissociated based on their activation time courses. CONCLUSIONS: The retro-splenial cortex is a dominant source of the parietal P3 maximum in EEG. SIGNIFICANCE: These results provide a new perspective for the interpretation of the extensive research based on the P3 response.

How anatomical asymmetry of human auditory cortex can lead to a rightward bias in auditory evoked fields.

Auditory evoked fields and potentials, such as the N1 or the 40-Hz steady state response, are often stronger in the right compared to the left auditory cortex. Here we investigated whether a greater degree of cortical folding in left auditory cortex could result in increased MEG signal cancelation and a subsequent bias in MEG auditory signals toward the right hemisphere. Signal cancelation, due to non-uniformity of the orientations of underlying neural currents, affects MEG and EEG signals generated by any neuronal activity of reasonable spatial extent. We simulated MEG signals in patches of auditory cortex in seventeen subjects, and measured the relationships between underlying activity distribution, cortical non-uniformity, signal cancelation and resulting (fitted) dipole strength and position. Our results suggest that the cancelation of MEG signals from auditory cortex is asymmetric, due to underlying anatomy, and this asymmetry may result in a rightward bias in measurable dipole amplitudes. The effect was significant across all auditory areas tested, with the exception of planum temporale. Importantly, we also show how the rightward bias could be partially or completely offset by increased cortical area, and therefore increased cortical activity, on the left side. We suggest that auditory researchers are aware of the impact of cancelation and its resulting rightward bias in signal strength from auditory cortex. These findings are important for studies seeking functional hemispheric specialization in the auditory cortex with MEG as well as for integration of MEG with other imaging modalities.

A role for retro-splenial cortex in the task-related P3 network.

Objective: The P3 is an event-related response observed in relation to task-relevant sensory events. Despite its ubiquitous presence, the neural generators of the P3 are controversial and not well identified. Methods: We compared source analysis of combined magneto- and electroencephalography (M/EEG) data with functional magnetic resonance imaging (fMRI) and simulation studies to better understand the sources of the P3 in an auditory oddball paradigm. Results: Our results suggest that the dominant source of the classical, postero-central P3 lies in the retro-splenial cortex of the ventral cingulate gyrus. A second P3 source in the anterior insular cortex contributes little to the postero-central maximum. Multiple other sources in the auditory, somatosensory, and anterior midcingulate cortex are active in an overlapping time window but can be functionally dissociated based on their activation time courses. Conclusion: The retro-splenial cortex is a dominant source of the parietal P3 maximum in EEG. Significance: These results provide a new perspective for the interpretation of the extensive research based on the P3 response.

Association between Type 2 Diabetes Mellitus and Brain Atrophy: A Meta-Analysis.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is known to be associated with cognitive decline and brain structural changes. This study systematically reviews and estimates human brain volumetric differences and atrophy associated with T2DM. METHODS: PubMed, PsycInfo and Cochrane Library were searched for brain imaging studies reporting on brain volume differences between individuals with T2DM and healthy controls. Data were examined using meta-analysis, and association between age, sex, diabetes characteristics and brain volumes were tested using meta-regression. RESULTS: A total of 14,605 entries were identified; after title, abstract and full-text screening applying inclusion and exclusion criteria, 64 studies were included and 42 studies with compatible data contributed to the meta-analysis (n=31,630; mean age 71.0 years; 44.4% male; 26,942 control; 4,688 diabetes). Individuals with T2DM had significantly smaller total brain volume, total grey matter volume, total white matter volume and hippocampal volume (approximately 1% to 4%); meta-analyses of smaller samples focusing on other brain regions and brain atrophy rate in longitudinal investigations also indicated smaller brain volumes and greater brain atrophy associated with T2DM. Meta-regression suggests that diabetes-related brain volume differences start occurring in early adulthood, decreases with age and increases with diabetes duration. CONCLUSION: T2DM is associated with smaller total and regional brain volume and greater atrophy over time. These effects are substantial and highlight an urgent need to develop interventions to reduce the risk of T2DM for brain health.

Default network connectivity during a working memory task.

The default network exhibits correlated activity at rest and has shown decreased activation during performance of cognitive tasks. There has been little investigation of changes in connectivity of this network during task performance. In this study, we examined task-related modulation of connectivity between two seed regions from the default network posterior cingulated cortex (PCC) and medial prefrontal cortex (mPFC) and the rest of the brain in 12 healthy adults. The purpose was to determine (1) whether connectivity within the default network differs between a resting state and performance of a cognitive (working memory) task and (2) whether connectivity differs between these nodes of the default network and other brain regions, particularly those implicated in cognitive tasks. There was little change in connectivity with the other main areas of the default network for either seed region, but moderate task-related changes in connectivity occurred between seed regions and regions outside the default network. For example, connectivity of the mPFC with the right insula and the right superior frontal gyrus decreased during task performance. Increased connectivity during the working memory task occurred between the PCC and bilateral inferior frontal gyri, and between the mPFC and the left inferior frontal gyrus, cuneus, superior parietal lobule, middle temporal gyrus and cerebellum. Overall, the areas showing greater correlation with the default network seed regions during task than at rest have been previously implicated in working memory tasks. These changes may reflect a decrease in the negative correlations occurring between the default and task-positive networks at rest.

Optimal Blood Pressure Keeps Our Brains Younger.

Background: Elevated blood pressure (BP) is a major health risk factor and the leading global cause of premature death. Hypertension is also a risk factor for cognitive decline and dementia. However, when elevated blood pressure starts impacting cerebral health is less clear. We addressed this gap by estimating how a validated measure of brain health relates to changes in BP over a period of 12 years. Methods: Middle-age (44-46 years at baseline, n = 335, 52% female) and older-age (60-64 years, n = 351, 46% female) cognitively intact individuals underwent up to four brain scans. Brain health was assessed using a machine learning approach to produce an estimate of "observed" age (BrainAGE), which can be contrasted with chronological age. Longitudinal associations between blood pressures and BrainAGE were assessed with linear mixed-effects models. Results: A progressive increase in BP was observed over the follow up (MAP = 0.8 mmHg/year, SD = 0.92; SBP = 1.41 mmHg/year, SD = 1.49; DBP = 0.61 mmHg/year, SD = 0.78). In fully adjusted models, every additional 10 mmHg increase in blood pressure (above 90 for mean, 114 for systolic, and 74 for diastolic blood pressure) was associated with a higher BrainAGE by 65.7 days for mean, and 51.1 days for systolic/diastolic blood pressure. These effects occurred across the blood pressure range and were not exclusively driven by hypertension. Conclusion: Increasing blood pressure is associated with poorer brain health. Compared to a person becoming hypertensive, somebody with an ideal BP is predicted to have a brain that appears more than 6 months younger at midlife.

Longitudinal trajectories of hippocampal volume in middle to older age community dwelling individuals.

Understanding heterogeneity in brain aging trajectories is important to estimate the extent to which aging outcomes can be optimized. Although brain changes in late life are well-characterized, brain changes in middle age are not well understood. In this study, we investigated hippocampal change in a generally healthy community-living population of middle (n = 421, mean age 47.2 years) and older age (n = 411, mean age 63.0 years) individuals, over a follow-up of up to 12 years. Manually traced hippocampal volumes were analyzed using multilevel models and latent class analysis to investigate longitudinal aging trajectories and laterality and sex effects, and to identify subgroups that follow different aging trajectories. Hippocampal volumes decreased on average by 0.18%/year in middle age and 0.3%/year in older age. Men tended to experience steeper declines than women in middle age only. Three subgroups of individuals following different trajectories were identified in middle age and 2 in older age. Contrary to expectations, the subgroup containing two-thirds of older age participants maintained stable hippocampal volumes across the follow-up.

Structural and functional neuroimaging changes associated with cognitive impairment and dementia in Parkinson's disease.

This study seeks a better understanding of possible pathophysiological mechanisms associated with cognitive impairment and dementia in Parkinson's disease using structural and functional MRI. We investigated resting-state functional connectivity of important subdivisions of the caudate nucleus, putamen and thalamus, and also how the morphology of these structures are impacted in the disorder. We found cognitively unimpaired Parkinson's disease subjects (n = 33), compared to controls (n = 26), display increased functional connectivity of the dorsal caudate, anterior putamen and mediodorsal thalamic subdivisions with areas across the frontal lobe, as well as reduced functional connectivity of the dorsal caudate with posterior cortical and cerebellar regions. Compared to cognitively unimpaired subjects, those with mild cognitive impairment (n = 22) demonstrated reduced functional connectivity of the mediodorsal thalamus with the paracingulate cortex, while also demonstrating increased functional connectivity of the mediodorsal thalamus with the posterior cingulate cortex, compared to subjects with dementia (n = 17). Extensive volumetric and surface-based deflation was found in subjects with dementia compared to cognitively unimpaired Parkinson's disease participants and controls. Our research suggests that structures within basal ganglia-thalamocortical circuits are implicated in cognitive impairment and dementia in Parkinson's disease, with cognitive impairment and dementia associated with a breakdown in functional connectivity of the mediodorsal thalamus with para- and posterior cingulate regions of the brain respectively.

Switching between executive and default mode networks in posttraumatic stress disorder: alterations in functional connectivity.

UNLABELLED: Working memory processing and resting-state connectivity in the default mode network are altered in patients with posttraumatic stress disorder (PTSD). Because the ability to effortlessly switch between concentration on a task and an idling state during rest is implicated in both these alterations, we undertook a functional magnetic resonance imaging study with a block design to analyze task-induced modulations in connectivity. METHODS: We performed a working memory task and psychophysiologic interaction analyses with the posterior cingulate cortex and the medial prefrontal cortex as seed regions during fixation in 12 patients with severe, chronic PTSD and 12 healthy controls. RESULTS: During the working memory task, the control group showed significantly stronger connectivity with areas implicated in the salience and executive networks, including the right inferior frontal gyrus and the right inferior parietal lobule. The PTSD group showed stronger connectivity with areas implicated in the default mode network, namely enhanced connectivity between the posterior cingulate cortex and the right superior frontal gyrus and between the medial prefrontal cortex and the left parahippocampal gyrus. LIMITATIONS: Because we were studying alterations in patients with severe, chronic PTSD, we could not exclude patients taking medication. The small sample size may have limited the power of our analyses. To avoid multiple testing in a small sample, we only used 2 seed regions for our analyses. CONCLUSION: The different patterns of connectivity imply significant group differences with task-induced switches (i.e., engaging and disengaging the default mode network and the central-executive network).