fMRI activation detection with EEG priors

The purpose of brain mapping techniques is to advance the understanding of the relationship between structure and function in the human brain in so-called activation studies. In this work, an advanced statistical model for combining functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) recordings is developed to fuse complementary information about the location of neuronal activity. More precisely, a new Bayesian method is proposed for enhancing fMRI activation detection by the use of EEG-based spatial prior information in stimulus based experimental paradigms. I.e., we model and analyse stimulus influence by a spatial Bayesian variable selection scheme, and extend existing high-dimensional regression methods by incorporating prior information on binary selection indicators via a latent probit regression with either a spatially-varying or constant EEG effect. Spatially-varying effects are regularized by intrinsic Markov random field priors. Inference is based on a full Bayesian Markov Chain Monte Carlo (MCMC) approach. Whether the proposed algorithm is able to increase the sensitivity of mere fMRI models is examined in both a real-world application and a simulation study. We observed, that carefully selected EEG--prior information additionally increases sensitivity in activation regions that have been distorted by a low signal-to-noise ratio

Frontoparietal Connectivity and Hierarchical Structure of the Brain’s Functional Network during Sleep

Frontal and parietal regions are associated with some of the most complex cognitive functions, and several frontoparietal resting-state networks can be observed in wakefulness. We used functional magnetic resonance imaging data acquired in polysomnographically validated wakefulness, light sleep, and slow-wave sleep to examine the hierarchical structure of a low-frequency functional brain network, and to examine whether frontoparietal connectivity would disintegrate in sleep. Whole-brain analyses with hierarchical cluster analysis on predefined atlases were performed, as well as regression of inferior parietal lobules (IPL) seeds against all voxels in the brain, and an evaluation of the integrity of voxel time-courses in subcortical regions-of-interest. We observed that frontoparietal functional connectivity disintegrated in sleep stage 1 and was absent in deeper sleep stages. Slow-wave sleep was characterized by strong hierarchical clustering of local submodules. Frontoparietal connectivity between IPL and superior medial and right frontal gyrus was lower in sleep stages than in wakefulness. Moreover, thalamus voxels showed maintained integrity in sleep stage 1, making intrathalamic desynchronization an unlikely source of reduced thalamocortical connectivity in this sleep stage. Our data suggest a transition from a globally integrated functional brain network in wakefulness to a disintegrated network consisting of local submodules in slow-wave sleep, in which frontoparietal inter-modular nodes may play a role, possibly in combination with the thalamus

Unstable Prefrontal Response to Emotional Conflict and Activation of Lower Limbic Structures and Brainstem in Remitted Panic Disorder

Background: The neural mechanisms of panic disorder (PD) are only incompletely understood. Higher sensitivity of patients to unspecific fear cues and similarities to conditioned fear suggest involvement of lower limbic and brainstem structures. We investigated if emotion perception is altered in remitted PD as a trait feature. Methodology/Principal Findings: We used blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) to study neural and behavioural responses of 18 remitted PD patients and 18 healthy subjects to the emotional conflict paradigm that is based on the presentation of emotionally congruent and incongruent face/word pairs. We observed that patients showed stronger behavioural interference and lower adaptation to interference conflict. Overall performance in patients was slower but not less accurate. In the context of preceding congruence, stronger dorsal anterior cingulate cortex (dACC) activation during conflict detection was found in patients. In the context of preceding incongruence, controls expanded dACC activity and succeeded in reducing behavioural interference. In contrast, patients demonstrated a dropout of dACC and dorsomedial prefrontal cortex (dmPFC) recruitment but activation of the lower limbic areas (including right amygdala) and brainstem. Conclusions/Significance: This study provides evidence that stimulus order in the presentation of emotional stimuli has a markedly larger influence on the brain’s response in remitted PD than in controls, leading to abnormal responses of th

Tau protein is essential for stress-induced brain pathology

Exposure to chronic stress is frequently accompanied by cognitive and affective disorders in association with neurostructural adaptations. Chronic stress was previously shown to trigger Alzheimer's-like neuropathology, which is characterized by Tau hyper-phosphorylation and missorting into dendritic spines followed by memory deficits. Here, we demonstrate that stress-driven hippocampal deficits in wild-type mice are accompanied by synaptic missorting of Tau and enhanced Fyn/GluN2B-driven synaptic signaling. In contrast, mice lacking Tau [Tau knockout (Tau-KO) mice] do not exhibit stress-induced pathological behaviors and atrophy of hippocampal dendrites or deficits of hippocampal connectivity. These findings implicate Tau as an essential mediator of the adverse effects of stress on brain structure and function.We thank Dr. Peter Davies (Albert Einstein College) for the PHF1 antibody. This work was funded by Portuguese Foundation for Science & Technology (FCT) Grants PTDC/SAU-NMC/113934/2009 (to I.S.); the European Union FP7 Project SwitchBox (N.S. and O.F.X.A.); the Portuguese North Regional Operational Program (ON.2-O Novo Norte) under the National Strategic Reference Framework (QREN) through the European Regional Development Fund (FEDER); and the Education and Lifelong Learning, Supporting Postdoctoral Researchers and Large Scale Cooperative Project, cofinanced by the European Social Fund and the Greek General Secretariat for Research and Technology. J.V.-S. is a recipient of a PhD fellowship (PD/BD/105938/2014) of the University of Minho MD/PhD Program funded by the FCT

Medial Prefrontal-Hippocampal Connectivity and Motor Memory Consolidation in Depression and Schizophrenia

Item does not contain fulltextBACKGROUND: Overnight memory consolidation is disturbed in both depression and schizophrenia, creating an ideal situation to investigate the mechanisms underlying sleep-related consolidation and to distinguish disease-specific processes from common elements in their pathophysiology. METHODS: We investigated patients with depression and schizophrenia, as well as healthy control subjects (each n = 16), under a motor memory consolidation protocol with functional magnetic resonance imaging and polysomnography. RESULTS: In a sequential finger-tapping task associated with the degree of hippocampal-prefrontal cortex functional connectivity during the task, significantly less overnight improvement was identified as a common deficit in both patient groups. A task-related overnight decrease in activation of the basal ganglia was observed in control subjects and schizophrenia patients; in contrast, patients with depression showed an increase. During the task, schizophrenia patients, in comparison with control subjects, additionally recruited adjacent cortical areas, which showed a decrease in functional magnetic resonance imaging activation overnight and were related to disease severity. Effective connectivity analyses revealed that the hippocampus was functionally connected to the motor task network, and the cerebellum decoupled from this network overnight. CONCLUSIONS: While both patient groups showed similar deficits in consolidation associated with hippocampal-prefrontal cortex connectivity, other activity patterns more specific for disease pathology differed.10 p

Acoustic Oddball during NREM Sleep: A Combined EEG/fMRI Study

Background: A condition vital for the consolidation and maintenance of sleep is generally reduced responsiveness to external stimuli. Despite this, the sleeper maintains a level of stimulus processing that allows to respond to potentially dangerous environmental signals. The mechanisms that subserve these contradictory functions are only incompletely understood. Methodology/Principal Findings: Using combined EEG/fMRI we investigated the neural substrate of sleep protection by applying an acoustic oddball paradigm during light NREM sleep. Further, we studied the role of evoked K-complexes (KCs), an electroencephalographic hallmark of NREM sleep with a still unknown role for sleep protection. Our main results were: (1) Other than in wakefulness, rare tones did not induce a blood oxygenation level dependent (BOLD) signal increase in the auditory pathway but a strong negative BOLD response in motor areas and the amygdala. (2) Stratification of rare tones by the presence of evoked KCs detected activation of the auditory cortex, hippocampus, superior and middle frontal gyri and posterior cingulate only for rare tones followed by a KC. (3) The typical high frontocentral EEG deflections of KCs were not paralleled by a BOLD equivalent. Conclusions/Significance: We observed that rare tones lead to transient disengagement of motor and amygdala responses during light NREM sleep. We interpret this as a sleep protective mechanism to delimit motor responses and to reduce the sensitivity of the amygdala towards further incoming stimuli. Evoked KCs are suggested to originate from a brain state wit

Low Prevalence of Isolated Growth Hormone Deficiency in Patients After Brain Injury: Results From a Phase II Pilot Study

Growth hormone deficiency (GHD) results in an impaired health-related quality of life (HrQoL) and cognitive impairment in the attention and memory domain. GHD is assumed to be a frequent finding after brain injury due to traumatic brain injury (TBI), aneurysmal subarachnoid hemorrhage (SAH) or ischemic stroke. Hence, we set out to investigate the effects of growth hormone (GH) replacement therapy in patients with isolated GHD after brain injury on HrQoL, cognition, and abdominal fat composition. In total, 1,408 patients with TBI, SAH or ischemic stroke were screened for inclusion. Of those, 54 patients (age 18-65 years) were eligible, and 51 could be tested for GHD with GHRH-L-arginine. In 6 patients (12%), GHD was detected. All patients with isolated GHD (n = 4 [8%], male, mean age +/- SD: 49.0 +/- 9.8 years) received GH replacement therapy for 6 months at a daily dose of 0.2-0.5 mg recombinant GH depending on age. Results were compared with an untreated control group of patients without hormonal insufficiencies after brain injury (n = 6, male, mean age +/- SD: 49.5 +/- 13.6 years). HrQoL as well as mood and sleep quality assessed by self-rating questionnaires (Beck Depression Index, Pittsburgh Sleep Quality Index) did not differ between baseline and 6 months within each group or between the two groups. Similarly, cognitive performance as assessed by standardized memory and attention tests did not show significant differences within or between groups. Body mass index was higher in the control vs. the GH replacement group at baseline (p = 0.038), yet not different at 6 months and within groups. Visceral-fat-by-total-fat-ratio measurements obtained from magnetic resonance imaging in 2 patients and 5 control subjects exhibited no consistent pattern. In conclusion, this single center study revealed a prevalence of GHD of about 12% (8% with isolated GHD) in brain injury patients which was lower compared with most of the previously reported cohorts. As a consequence, the sample size was insufficient to conclude on a benefit or no benefit of GH replacement in patients with isolated GHD after brain injury. A higher number of patients will be necessary to draw conclusions in future studies

Atypical processing of voice sounds in infants at risk for Autism Spectrum Disorder

Adults diagnosed with autism spectrum disorder (ASD) show a reduced sensitivity (degree of selective response) to social stimuli such as human voices. In order to determine whether this reduced sensitivity is a consequence of years of poor social interaction and communication or is present prior to significant experience, we used functional MRI to examine cortical sensitivity to auditory stimuli in infants at high familial risk for later emerging ASD (HR group, N = 15), and compared this to infants with no family history of ASD (LR group, N = 18). The infants (aged between 4 and 7 months) were presented with voice and environmental sounds while asleep in the scanner and their behaviour was also examined in the context of observed parent-infant interaction. Whereas LR infants showed early specialisation for human voice processing in right temporal and medial frontal regions, the HR infants did not. Similarly, LR infants showed stronger sensitivity than HR infants to sad vocalisations in the right fusiform gyrus and left hippocampus. Also, in the HR group only, there was an association between each infant's degree of engagement during social interaction and the degree of voice sensitivity in key cortical regions. These results suggest that at least some infants at high-risk for ASD have atypical neural responses to human voice with and without emotional valence. Further exploration of the relationship between behaviour during social interaction and voice processing may help better understand the mechanisms that lead to different outcomes in at risk populations

Novel genetic loci associated with hippocampal volume

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness

Novel genetic loci underlying human intracranial volume identified through genome-wide association

Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five novel loci for intracranial volume and confirmed two known signals. Four of the loci are also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (ρgenetic=0.748), which indicated a similar genetic background and allowed for the identification of four additional loci through meta-analysis (Ncombined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, Parkinson’s disease, and enriched near genes involved in growth pathways including PI3K–AKT signaling. These findings identify biological underpinnings of intracranial volume and provide genetic support for theories on brain reserve and brain overgrowth