Executive Control and Associated Brain Activity in Children With Familial High-Risk of Schizophrenia or Bipolar Disorder: A Danish Register-based Study.

BACKGROUND AND HYPOTHESES: Impaired executive control is a potential prognostic and endophenotypic marker of schizophrenia (SZ) and bipolar disorder (BP). Assessing children with familial high-risk (FHR) of SZ or BP enables characterization of early risk markers and we hypothesize that they express impaired executive control as well as aberrant brain activation compared to population-based control (PBC) children. STUDY DESIGN: Using a flanker task, we examined executive control together with functional magnetic resonance imaging (fMRI) in 11- to 12-year-old children with FHR of SZ (FHR-SZ) or FHR of BP (FHR-BP) and PBC children as part of a register-based, prospective cohort-study; The Danish High Risk and Resilience study-VIA 11. STUDY RESULTS: We included 85 (44% female) FHR-SZ, 63 (52% female) FHR-BP and 98 (50% female) PBC in the analyses. Executive control effects, caused by the spatial visuomotor conflict, showed no differences between groups. Bayesian ANOVA of reaction time (RT) variability, quantified by the coefficient of variation (CVRT), revealed a group effect with similarly higher CVRT in FHR-BP and FHR-SZ compared to PBC (BF10 = 6.82). The fMRI analyses revealed no evidence for between-group differences in task-related brain activation. Post hoc analyses excluding children with psychiatric illness yielded same results. CONCLUSION: FHR-SZ and FHR-BP at age 11-12 show intact ability to resolve a spatial visuomotor conflict and neural efficacy. The increased variability in RT may reflect difficulties in maintaining sustained attention. Since variability in RT was independent of existing psychiatric illness, it may reflect a potential endophenotypic marker of risk.

Improved sensitivity and microvascular weighting of 3T laminar fMRI with GE-BOLD using NORDIC and phase regression.

INTRODUCTION: Functional MRI with spatial resolution in the submillimeter domain enables measurements of activation across cortical layers in humans. This is valuable as different types of cortical computations, e.g., feedforward versus feedback related activity, take place in different cortical layers. Laminar fMRI studies have almost exclusively employed 7T scanners to overcome the reduced signal stability associated with small voxels. However, such systems are relatively rare and only a subset of those are clinically approved. In the present study, we examined if the feasibility of laminar fMRI at 3T could be improved by use of NORDIC denoising and phase regression. METHODS: 5 healthy subjects were scanned on a Siemens MAGNETOM Prisma 3T scanner. To assess across-session reliability, each subject was scanned in 3-8 sessions on 3-4 consecutive days. A 3D gradient echo EPI (GE-EPI) sequence was used for BOLD acquisitions (voxel size 0.82 mm isotopic, TR = 2.2 s) using a block design finger tapping paradigm. NORDIC denoising was applied to the magnitude and phase time series to overcome limitations in temporal signal-to-noise ratio (tSNR) and the denoised phase time series were subsequently used to correct for large vein contamination through phase regression. RESULTS AND CONCLUSION: NORDIC denoising resulted in tSNR values comparable to or higher than commonly observed at 7T. Layer-dependent activation profiles could thus be extracted robustly, within and across sessions, from regions of interest located in the hand knob of the primary motor cortex (M1). Phase regression led to substantially reduced superficial bias in obtained layer profiles, although residual macrovascular contribution remained. We believe the present results support an improved feasibility of laminar fMRI at 3T.

A bias towards natural rewards away from gambling cues in gamblers undergoing active treatment.

BACKGROUND: Disorders of substance and behavioral addiction are believed to be associated with a myopic bias towards the incentive salience of addiction-related cues away from general rewards in the environment. In non-treatment seeking gambling disorder patients, neural activity to anticipation of monetary rewards is enhanced relative to erotic rewards. Here we focus on the balance between anticipation of reward types in active treatment gamblers relative to healthy volunteers. METHODS: Fifty-three (25 gambling disorder males, 28 age-matched male healthy volunteers) were scanned with fMRI performing a Monetary Incentive Delay task with monetary and erotic outcomes. RESULTS: During reward anticipation, gambling disorder was associated with greater left orbitofrontal cortex and ventral striatal activity to erotic relative to monetary reward anticipation compared to healthy volunteers. Lower impulsivity correlated with greater activity in the dorsal striatum and dorsal anterior cingulate cortex to erotic anticipation in gambling disorder subjects. In the outcome phase, gambling disorder subjects showed greater activity in the ventral striatum, ventromedial and dorsolateral prefrontal cortex and anterior cingulate cortex to both reward types relative to healthy volunteers. CONCLUSIONS: These findings contrast directly with previous findings in non-treatment seeking gambling disorder. Our observations highlight the role of treatment state in active treatment gambling disorder, emphasizing a potential influence of treatment status, gambling abstinence or cognitive behavioral therapy on increasing the salience of general rewards beyond that of gambling-related cues. These findings support a potential therapeutic role for targeting the salience of non-gambling related rewards and potential biomarkers for treatment efficacy.

Language beyond the language system: Dorsal visuospatial pathways support processing of demonstratives and spatial language during naturalistic fast fMRI.

Spatial demonstratives are powerful linguistic tools used to establish joint attention. Identifying the meaning of semantically underspecified expressions like "this one" hinges on the integration of linguistic and visual cues, attentional orienting and pragmatic inference. This synergy between language and extralinguistic cognition is pivotal to language comprehension in general, but especially prominent in demonstratives. In this study, we aimed to elucidate which neural architectures enable this intertwining between language and extralinguistic cognition using a naturalistic fMRI paradigm. In our experiment, 28 participants listened to a specially crafted dialogical narrative with a controlled number of spatial demonstratives. A fast multiband-EPI acquisition sequence (TR = 388 m s) combined with finite impulse response (FIR) modelling of the hemodynamic response was used to capture signal changes at word-level resolution. We found that spatial demonstratives bilaterally engage a network of parietal areas, including the supramarginal gyrus, the angular gyrus, and precuneus, implicated in information integration and visuospatial processing. Moreover, demonstratives recruit frontal regions, including the right FEF, implicated in attentional orienting and reference frames shifts. Finally, using multivariate similarity analyses, we provide evidence for a general involvement of the dorsal ("where") stream in the processing of spatial expressions, as opposed to ventral pathways encoding object semantics. Overall, our results suggest that language processing relies on a distributed architecture, recruiting neural resources for perception, attention, and extra-linguistic aspects of cognition in a dynamic and context-dependent fashion.

APOE gene-dependent BOLD responses to a breath-hold across the adult lifespan.

Age and apolipoprotein E (APOE) e4 genotype are two of the strongest known risk factors for sporadic Alzheimer's disease (AD). Neuroimaging has shown hemodynamic response changes with age, in asymptomatic carriers of the APOE e4 allele, and in AD. In this study, we aimed to characterize and differentiate age- and APOE gene-specific hemodynamic changes to breath-hold and visual stimulation. A further aim was to study whether these responses were modulated by 3-day intake of nitrate, a nitric oxide (NO) source. The study was designed as a randomized, double-blinded, placebo-controlled crossover study, and the study cohort comprised 41 APOE e4 carriers (e3/e4 or e4/e4 genotype) and 40 non-carriers (e3/e3 genotype) aged 30-70 years at enrollment. The participants underwent two scanning sessions, each preceded by ingestion of sodium nitrate or sodium chloride (control). During functional magnetic resonance imaging (fMRI) sessions, participants performed two concurrent tasks; a breath-hold task to probe cerebrovascular reactivity and a visual stimulation task to evoke functional hyperemia, respectively. We found that the blood oxygenation level dependent (BOLD) hemodynamic response to breath-hold was altered in APOE e4 carriers relative to non-carriers. Mid-aged (50-60 years of age) e4 carriers exhibited a significantly increased peak time relative to mid-aged e3 carriers, and peak time for younger (30-40 years of age) e4 carriers was significantly shorter than that of mid-aged e4 carriers. The response width was significantly increased for e4 carriers. The response peak magnitude significantly decreased with age. For the visual stimulation task, we found age-related changes, with reduced response magnitude with age but no significant effect of APOE allele type. We found no effect of nitrate ingestion on BOLD responses evoked by the breath-hold and visual stimulation tasks. The APOE gene-dependent response to breath-hold may reflect NO-independent differences in vascular function.

Rapid solution of the Bloch-Torrey equation in anisotropic tissue: Application to dynamic susceptibility contrast MRI of cerebral white matter.

Blood vessel related magnetic resonance imaging (MRI) contrast provides a window into the brain's metabolism and function. Here, we show that the spin echo dynamic susceptibility contrast (DSC) MRI signal of the brain's white matter (WM) strongly depends on the angle between WM tracts and the main magnetic field. The apparent cerebral blood flow and volume are 20% larger in fibres perpendicular to the main magnetic field compared to parallel fibres. We present a rapid numerical framework for the solution of the Bloch-Torrey equation that allows us to explore the isotropic and anisotropic components of the vascular tree. By fitting the simulated spin echo DSC signal to the measured data, we show that half of the WM vascular volume is comprised of vessels running in parallel with WM fibre tracts. The WM blood volume corresponding to the best fit to the experimental data was 2.82%, which is close to the PET gold standard of 2.6%.

Using automated electrode localization to guide stimulation management in DBS.

Deep Brain Stimulation requires extensive postoperative testing of stimulation parameters to achieve optimal outcomes. Testing is typically not guided by neuroanatomical information on electrode contact locations. To address this, we present an automated reconstruction of electrode locations relative to the treatment target, the subthalamic nucleus, comparing different targeting methods: atlas-, manual-, or tractography-based subthalamic nucleus segmentation. We found that most electrode contacts chosen to deliver stimulation were closest or second closest to the atlas-based subthalamic nucleus target. We suggest that information on each electrode contact's location, which can be obtained using atlas-based methods, might guide clinicians during postoperative stimulation testing.

Brain inflammation accompanies amyloid in the majority of mild cognitive impairment cases due to Alzheimer's disease.

See Kreisl (doi:10.1093/awx151) for a scientific commentary on this article.Subjects with mild cognitive impairment associated with cortical amyloid-ß have a greatly increased risk of progressing to Alzheimer's disease. We hypothesized that neuroinflammation occurs early in Alzheimer's disease and would be present in most amyloid-positive mild cognitive impairment cases. 11C-Pittsburgh compound B and 11C-(R)-PK11195 positron emission tomography was used to determine the amyloid load and detect the extent of neuroinflammation (microglial activation) in 42 mild cognitive impairment cases. Twelve age-matched healthy control subjects had 11C-Pittsburgh compound B and 10 healthy control subjects had 11C-(R)-PK11195 positron emission tomography for comparison. Amyloid-positivity was defined as 11C-Pittsburgh compound B target-to-cerebellar ratio above 1.5 within a composite cortical volume of interest. Supervised cluster analysis was used to generate parametric maps of 11C-(R)-PK11195 binding potential. Levels of 11C-(R)-PK11195 binding potential were measured in a selection of cortical volumes of interest and at a voxel level. Twenty-six (62%) of 42 mild cognitive impairment cases showed a raised cortical amyloid load compared to healthy controls. Twenty-two (85%) of the 26 amyloid-positive mild cognitive impairment cases showed clusters of increased cortical microglial activation accompanying the amyloid. There was a positive correlation between levels of amyloid load and 11C-(R)-PK11195 binding potentials at a voxel level within subregions of frontal, parietal and temporal cortices. 11C-(R)-PK11195 positron emission tomography reveals increased inflammation in a majority of amyloid positive mild cognitive impairment cases, its cortical distribution overlapping that of amyloid deposition.

White matter biomarkers from fast protocols using axially symmetric diffusion kurtosis imaging.

White matter tract integrity (WMTI) can characterize brain microstructure in areas with highly aligned fiber bundles. Several WMTI biomarkers have now been validated against microscopy and provided promising results in studies of brain development and aging, as well as in a number of brain disorders. Currently, WMTI is mostly used in dedicated animal studies and clinical studies of slowly progressing diseases, and has not yet emerged as a routine clinical tool. To this end, a less data intensive experimental method would be beneficial by enabling high resolution validation studies, and ease clinical applications by speeding up data acquisition compared with typical diffusion kurtosis imaging (DKI) protocols utilized as part of WMTI imaging. Here, we evaluate WMTI based on recently introduced axially symmetric DKI, which has lower data demand than conventional DKI. We compare WMTI parameters derived from conventional DKI with those calculated analytically from axially symmetric DKI. We employ numerical simulations, as well as data from fixed rat spinal cord (one sample) and in vivo human (three subjects) and rat brain (four animals). Our analysis shows that analytical WMTI based on axially symmetric DKI with sparse data sets (19 images) produces WMTI metrics that correlate strongly with estimates based on traditional DKI data sets (60 images or more). We demonstrate the preclinical potential of the proposed WMTI technique in in vivo rat brain (300 µm isotropic resolution with whole brain coverage in a 1 h acquisition). WMTI parameter estimates are subject to a duality leading to two solution branches dependent on a sign choice, which is currently debated. Results from both of these branches are presented and discussed throughout our analysis. The proposed fast WMTI approach may be useful for preclinical research and e.g. clinical evaluation of patients with traumatic white matter injuries or symptoms of neurovascular or neuroinflammatory disorders.

Probabilistic versus deterministic tractography for delineation of the cortico-subthalamic hyperdirect pathway in patients with Parkinson disease selected for deep brain stimulation.

OBJECTIVE Diffusion-weighted MRI (DWI) and tractography allows noninvasive mapping of the structural connections of the brain, and may provide important information for neurosurgical planning. The hyperdirect pathway, connecting the subthalamic nucleus (STN) with the motor cortex, is assumed to play a key role in mediating the effects of deep brain stimulation (DBS), which is an effective but poorly understood treatment for Parkinson disease. This study aimed to apply recent methodological advances in DWI acquisition and analysis to the delineation of the hyperdirect pathway in patients with Parkinson disease selected for surgery. METHODS High spatial and angular resolution DWI data were acquired preoperatively from 5 patients with Parkinson disease undergoing DBS. The authors compared the delineated hyperdirect pathways and associated STN target maps generated by 2 different tractography methods: a tensor-based deterministic method, typically available in clinical settings, and an advanced probabilistic method based on constrained spherical deconvolution. In addition, 10 high-resolution data sets with the same scanning parameters were acquired from a healthy control participant to assess the robustness of the tractography results. RESULTS Both tractography approaches identified connections between the ipsilateral motor cortex and the STN. However, the 2 methods provided substantially different target regions in the STN, with the target center of gravity differing by > 1.4 mm on average. The probabilistic method (based on constrained spherical deconvolution) plausibly reconstructed a continuous set of connections from the motor cortex, terminating in the dorsolateral region of the STN. In contrast, the tensor-based method reconstructed a comparatively sparser and more variable subset of connections. Furthermore, across the control scans, the probabilistic method identified considerably more consistent targeting regions within the STN compared with the deterministic tensor-based method, which demonstrated a 1.9-2.4 times higher variation. CONCLUSIONS These data provide a strong impetus for the use of a robust probabilistic tractography framework based on constrained spherical deconvolution, or similar advanced DWI models, in clinical settings. The inherent limitations and demonstrated inaccuracy of the tensor-based method leave it questionable for use in high-precision stereotactic DBS surgery. The authors have also described a straightforward method for importing tractography-derived information into any clinical neuronavigation system, based on the generation of track-density images.

Increased cortical capillary transit time heterogeneity in Alzheimer's disease: a DSC-MRI perfusion study.

Alzheimer's disease (AD) is characterized by the accumulation of hyperphosphorylated tau and neurotoxic Aß in the brain parenchyma. Hypoxia caused by microvascular changes and disturbed capillary flows could stimulate this build-up of AD-specific proteins in the brain. In this study, we compared cerebral microcirculation in a cohort of AD and mild cognitive impairment (MCI) patients with that of age-matched controls, all without a history of diabetes or of hypertension for more than 2 years, using dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI). Vascular flow disturbances were quantified using a parametric model and mapped to the mid-cortical surface for group-wise statistical analysis. We found widespread hypoperfusion in patients compared with controls and identified areas of increased relative capillary transit time heterogeneity (RTH), consistent with low tissue oxygen tension. Notably, RTH was positively correlated with white matter hyperintensities and positively correlated with symptom severity in the patient cohort. These correlations extended over large parts of the temporal, parietal, and frontal cortices. The results support the hypothesis of disturbed capillary flow patterns in AD and suggest that DSC-MRI may provide imaging biomarkers of impaired cerebral microcirculation in AD.

Experimental considerations for fast kurtosis imaging.

PURPOSE: The clinical use of kurtosis imaging is impeded by long acquisitions and postprocessing. Recently, estimation of mean kurtosis tensor W¯ and mean diffusivity ( D¯) was made possible from 13 distinct diffusion weighted MRI acquisitions (the 1-3-9 protocol) with simple postprocessing. Here, we analyze the effects of noise and nonideal diffusion encoding, and propose a new correction strategy. We also present a 1-9-9 protocol with increased robustness to experimental imperfections and minimal additional scan time. This refinement does not affect computation time and also provides a fast estimate of fractional anisotropy (FA). THEORY AND METHODS: 1-3-9/1-9-9 data are acquired in rat and human brains, and estimates of D¯, FA, W¯ from human brains are compared with traditional estimates from an extensive diffusion kurtosis imaging data set. Simulations are used to evaluate the influence of noise and diffusion encodings deviating from the scheme, and the performance of the correction strategy. Optimal b-values are determined from simulations and data. RESULTS: Accuracy and precision in D¯ and W¯ are comparable to nonlinear least squares estimation, and is improved with the 1-9-9 protocol. The compensation strategy vastly improves parameter estimation in nonideal data. CONCLUSION: The framework offers a robust and compact method for estimating several diffusion metrics. The protocol is easily implemented. Magn Reson Med 76:1455-1468, 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.

Dietary nitrate facilitates an acetazolamide-induced increase in cerebral blood flow during visual stimulation.

The carbonic anhydrase (CA) inhibitor acetazolamide (AZ) is used routinely to estimate cerebrovascular reserve capacity in patients, as it reliably increases cerebral blood flow (CBF). However, the mechanism by which AZ accomplishes this CBF increase is not entirely understood. We recently discovered that CA can produce nitric oxide (NO) from nitrite, and that AZ enhances this NO production in vitro. In fact, this interaction between AZ and CA accounted for a large part of AZ's vasodilatory action, which fits well with the known vasodilatory potency of NO. The present study aimed to assess whether AZ acts similarly in vivo in the human cerebrovascular system. Hence, we increased or minimized the dietary intake of nitrate in 20 healthy male participants, showed them a full-field flickering dartboard, and measured their CBF response to this visual stimulus with arterial spin labeling. Doing so, we found a significant positive interaction between the dietary intake of nitrate and the CBF modulation afforded by AZ during visual stimulation. In addition, but contrary to studies conducted in elderly participants, we report no effect of nitrate intake on resting CBF in healthy human participants. The present study provides in vivo support for an enhancing effect of AZ on the NO production from nitrite catalyzed by CA in the cerebrovascular system. Furthermore, our results, in combination with the results of other groups, indicate that nitrate may have significant importance to vascular function when the cerebrovascular system is challenged by age or disease.

A NO way to BOLD? Dietary nitrate alters the hemodynamic response to visual stimulation.

Neurovascular coupling links neuronal activity to vasodilation. Nitric oxide (NO) is a potent vasodilator, and in neurovascular coupling NO production from NO synthases plays an important role. However, another pathway for NO production also exists, namely the nitrate-nitrite-NO pathway. On this basis, we hypothesized that dietary nitrate (NO3-) could influence the brain's hemodynamic response to neuronal stimulation. In the present study, 20 healthy male participants were given either sodium nitrate (NaNO3) or sodium chloride (NaCl) (saline placebo) in a crossover study and were shown visual stimuli based on the retinotopic characteristics of the visual cortex. Our primary measure of the hemodynamic response was the blood oxygenation level dependent (BOLD) response measured with high-resolution functional magnetic resonance imaging (0.64×0.64×1.8 mm) in the visual cortex. From this response, we made a direct estimate of key parameters characterizing the shape of the BOLD response (i.e. lag and amplitude). During elevated nitrate intake, corresponding to the nitrate content of a large plate of salad, both the hemodynamic lag and the BOLD amplitude decreased significantly (7.0±2% and 7.9±4%, respectively), and the variation across activated voxels of both measures decreased (12.3±4% and 15.3±7%, respectively). The baseline cerebral blood flow was not affected by nitrate. Our experiments demonstrate, for the first time, that dietary nitrate may modulate the local cerebral hemodynamic response to stimuli. A faster and smaller BOLD response, with less variation across local cortex, is consistent with an enhanced hemodynamic coupling during elevated nitrate intake. These findings suggest that dietary patterns, via the nitrate-nitrite-NO pathway, may be a potential way to affect key properties of neurovascular coupling. This could have major clinical implications, which remain to be explored.

From Vivaldi to Beatles and back: predicting lateralized brain responses to music.

We aimed at predicting the temporal evolution of brain activity in naturalistic music listening conditions using a combination of neuroimaging and acoustic feature extraction. Participants were scanned using functional Magnetic Resonance Imaging (fMRI) while listening to two musical medleys, including pieces from various genres with and without lyrics. Regression models were built to predict voxel-wise brain activations which were then tested in a cross-validation setting in order to evaluate the robustness of the hence created models across stimuli. To further assess the generalizability of the models we extended the cross-validation procedure by including another dataset, which comprised continuous fMRI responses of musically trained participants to an Argentinean tango. Individual models for the two musical medleys revealed that activations in several areas in the brain belonging to the auditory, limbic, and motor regions could be predicted. Notably, activations in the medial orbitofrontal region and the anterior cingulate cortex, relevant for self-referential appraisal and aesthetic judgments, could be predicted successfully. Cross-validation across musical stimuli and participant pools helped identify a region of the right superior temporal gyrus, encompassing the planum polare and the Heschl's gyrus, as the core structure that processed complex acoustic features of musical pieces from various genres, with or without lyrics. Models based on purely instrumental music were able to predict activation in the bilateral auditory cortices, parietal, somatosensory, and left hemispheric primary and supplementary motor areas. The presence of lyrics on the other hand weakened the prediction of activations in the left superior temporal gyrus. Our results suggest spontaneous emotion-related processing during naturalistic listening to music and provide supportive evidence for the hemispheric specialization for categorical sounds with realistic stimuli. We herewith introduce a powerful means to predict brain responses to music, speech, or soundscapes across a large variety of contexts.

Sampling rate dependence of correlation at long time lags in BOLD fMRI measurements on humans and gel phantoms.

The aim of this study is to investigate the effects of sampling rate on Hurst exponents derived from Blood Oxygenation Level Dependent functional Magnetic Resonance Imaging (BOLD fMRI) resting state time series. fMRI measurements were performed on 2 human subjects and a selection of gel phantoms. From these, Hurst exponents were calculated. It was found that low sampling rates induced non-trivial exponents at sharp material transitions, and that Hurst exponents of human measurements had a strong TR-dependence. The findings are compared to theoretical considerations regarding the fractional Gaussian noise model and resampling, and it is found that the implications are problematic. This result should have a direct influence on the way future studies of low-frequency variation in BOLD fMRI data are conducted, especially if the fractional Gaussian noise model is considered. We recommend either using a different model (examples of such are referenced in the conclusion), or standardizing experimental procedures along an optimal sampling rate.

Experimentally and computationally fast method for estimation of a mean kurtosis.

PURPOSE: Results from several recent studies suggest the magnetic resonance diffusion-derived metric mean kurtosis (MK) to be a sensitive marker for tissue pathology; however, lengthy acquisition and postprocessing time hamper further exploration. The purpose of this study is to introduce and evaluate a new MK metric and a rapid protocol for its estimation. METHODS: The protocol requires acquisition of 13 standard diffusion-weighted images, followed by linear combination of log diffusion signals, thus avoiding nonlinear optimization. The method was evaluated on an ex vivo rat brain and an in vivo human brain. Parameter maps were compared with MK estimated from a standard diffusion kurtosis imaging (DKI) data set comprising 160 diffusion-weighted images. RESULTS: The new MK displays remarkably similar contrast to MK, and the proposed protocol acquires the necessary data in less than 1 min for full human brain coverage, with a postprocessing time of a few seconds. Scan-rescan reproducibility was comparable with MK. CONCLUSION: The framework offers a robust and rapid method for estimating MK, with a protocol easily adapted on commercial scanners, as it requires only minimal modification of standard diffusion-weighting protocols. These properties make the method feasible in practically any clinical setting.

Healthy aging attenuates task-related specialization in the human medial temporal lobe.

Recent research on aging has established important links between the neurobiology of normal aging and age-related decline in episodic memory, yet the exact nature of this relationship is still unknown. Functional neuroimaging of regions such as the medial temporal lobe (MTL) have produced conflicting findings. Using functional magnetic resonance imaging (fMRI), we have recently shown that young healthy individuals show a stronger activation of the MTL during encoding of objects as compared with encoding of positions. Using the same encoding task, the present study addressed the question whether this greater MTL activation during encoding of objects varies with age. Fifty-four healthy individuals aged between 18 and 81 years underwent functional magnetic resonance imaging while they encoded and subsequently made new-old judgments on objects and positions. Region of interest (ROI) analysis of task related changes in the blood oxygen level-dependent (BOLD) signal was performed in native space after correction for gender effects and individual differences in cerebral blood flow. The hippocampus, amygdala, and parahippocampal, perirhinal, entorhinal, and temporopolar cortices of right and left hemisphere were defined as ROIs. Aging had an adverse effect on memory performance that was similar for memorizing objects or positions. In left and right MTL, relatively greater activation for object stimuli was attenuated in older individuals. Age-related attenuation in content specificity was most prominent in the recognition stage. During recognition, the larger response to objects gradually decreased with age in all ROIs apart from left temporopolar and entorhinal cortex. An age-related attenuation was also present during encoding, but only in right parahippocampus and amygdala. Our results suggest that memory-related processing in the MTL becomes gradually less sensitive to content during normal aging.

The power of charisma--perceived charisma inhibits the frontal executive network of believers in intercessory prayer.

This study used functional magnetic resonance imaging to investigate how assumptions about speakers' abilities changed the evoked BOLD response in secular and Christian participants who received intercessory prayer. We find that recipients' assumptions about senders' charismatic abilities have important effects on their executive network. Most notably, the Christian participants deactivated the frontal network consisting of the medial and the dorsolateral prefrontal cortex bilaterally in response to speakers who they believed had healing abilities. An independent analysis across subjects revealed that this deactivation predicted the Christian participants' subsequent ratings of the speakers' charisma and experience of God's presence during prayer. These observations point to an important mechanism of authority that may facilitate charismatic influence, a mechanism which is likely to be present in other interpersonal interactions as well.