Publisher Correction: Associations between subjective well-being and subcortical brain volumes.

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Associations between subjective well-being and subcortical brain volumes.

To study the underpinnings of individual differences in subjective well-being (SWB), we tested for associations of SWB with subcortical brain volumes in a dataset of 724 twins and siblings. For significant SWB-brain associations we probed for causal pathways using Mendelian Randomization (MR) and estimated genetic and environmental contributions from twin modeling. Another independent measure of genetic correlation was obtained from linkage disequilibrium (LD) score regression on published genome-wide association summary statistics. Our results indicated associations of SWB with hippocampal volumes but not with volumes of the basal ganglia, thalamus, amygdala, or nucleus accumbens. The SWB-hippocampus relations were nonlinear and characterized by lower SWB in subjects with relatively smaller hippocampal volumes compared to subjects with medium and higher hippocampal volumes. MR provided no evidence for an SWB to hippocampal volume or hippocampal volume to SWB pathway. This was in line with twin modeling and LD-score regression results which indicated non-significant genetic correlations. We conclude that low SWB is associated with smaller hippocampal volume, but that genes are not very important in this relationship. Instead other etiological factors, such as exposure to stress and stress hormones, may exert detrimental effects on SWB and the hippocampus to bring about the observed association.

Motoric response inhibition in finger movement and saccadic eye movement: a comparative study.

OBJECTIVE: To study cortical potentials associated with suppression of intended motoric actions. METHODS: Electro-encephalographic activity was recorded in a Go/NoGo reaction time paradigm. Subjects viewed computer-generated pacing stimuli, which provided information concerning the time at which an imperative Go/NoGo signal occurred. A motoric response was required following Go stimuli while motoric response inhibition was required following NoGo stimuli. To examine whether previously reported 'Go/NoGo effects' on event related potential (ERP) components may be generalized across movement modalities, the present experimental paradigm was performed with either finger movement or saccadic eye movement as required motoric response. RESULTS: For both movement modalities, comparable differences in the morphology, amplitude and scalp topography of ERP components were observed between Go trials, with proper movement execution, and NoGo trials, with complete suppression of motoric activity. In addition, for either movement modality a similar 'error related negativity' (ERN) was found for NoGo trials in which motoric activity was present. CONCLUSIONS: The results of the present study suggest that cortical activity underlying the Go/NoGo differences in ERP components represent general cortical processing associated with detection and/or suppression of inappropriate response behaviour, independent of movement modality.

Spike cluster analysis in neocortical localization related epilepsy yields clinically significant equivalent source localization results in magnetoencephalogram (MEG).

OBJECTIVE: In magnetoencephalogram (MEG) recordings of patients with epilepsy several types of sharp transients with different spatiotemporal distributions are commonly present. Our objective was to develop a computer based method to identify and classify groups of epileptiform spikes, as well as other transients, in order to improve the characterization of irritative areas in the brain of epileptic patients. METHODS: MEG data centered on selected spikes were stored in signal matrices of C channels by T time samples. The matrices were normalized and euclidean distances between spike representations in vector space R(CxT) were input to a Ward's hierarchical clustering algorithm. RESULTS: The method was applied to MEG data from 4 patients with localization-related epilepsy. For each patient, distinct spike subpopulations were found with clearly different topographical field maps. Inverse computations to selected spike subaverages yielded source solutions in agreement with seizure classification and location of structural lesions, if present, on magnetic resonance images. CONCLUSIONS: With the proposed method a reliable categorization of epileptiform spikes is obtained, that can be applied in an automatic way. Computation of subaverages of similar spikes enhances the signal-to-noise ratio of spike field maps and allows for more accurate reconstruction of sources generating the epileptiform discharges.

The use of an MEG device as 3D digitizer and motion monitoring system.

An algorithm is described that localizes a set of simultaneously activated coils using MEG detectors. These coil positions are used for continuous or intermittent head position registration during long MEG sessions, to coregistrate MR and MEG data and to localize EEG electrodes attached to the scalp, when EEG and MEG are recorded simultaneously. The algorithm is based on a mathematical model in which the coils are described as stationary magnetic dipoles with known source time functions. This knowledge makes it possible to detect and remove bad channels automatically. It is also assumed that the source time functions are orthogonal. Therefore, the localization problem splits into independent localization problems. for each coil. The method is validated in a phantom experiment, where the relative coil positions were known. From this experiment it is found that the average error is 0.25 cm. An error of 0.23 cm was found in an experiment where 64 electrode positions were measured four times independently. Examples of the applications of the method are presented. Our method eliminates the use of an external 3D digitizer and maps the MEG directly onto other modalities. This is not only a practical advantage, but it also reduces the gross registration error. Furthermore, head motions can be monitored and MEG data can be corrected for these motions.

A fast method to derive realistic BEM models for E/MEG source reconstruction.

A fast method for segmentation of a subject's skin, skull or brain compartment for electroencephalogram (EEG)/magnetoencephalogram (MEG) (E/MEG) source localization is proposed. The method is based on a description of volumes with spherical harmonics and a database of exact surfaces. Using the spherical harmonic coefficients, sets of basis surfaces are obtained for each compartment. New segmentations can be acquired by combining the appropriate basis surfaces to describe a delineation of the volume in a limited number of magnetic resonance (MR) slices. Alternatively, a representation of the skin can be derived from digitized head shape. Skull and brain then can be predicted from the skin representation with a prediction model also obtained from the segmentation database. Database segmentations were recomputed with the proposed method. Mean deviations from the originals were about 2 and 3 mm for compartments derived from MR and head shape. Dipole simulations with original surfaces for forward and computed segmentations for inverse calculations showed average dipole mislocalizations of 1.6 and 3.3 mm, respectively. With the proposed method highly accurate segmentation can be performed with much less effort and in much less time compared with other techniques. The method also is applicable when MR data is unavailable but a digitization of the head is.

The use of fMRI to detect neural responses to cognitive interference and planning: evidence for a contribution of task related changes in heart rate?

fMRI signals during rest are strongly correlated with heart rate variations. These heart rate/fMRI associations may influence the results of brain activation studies, particularly if heart rate is affected by the task. To assess the contribution of task-related heart rate changes on fMRI brain activation related to executive processing, we co-registered the electrocardiogram with fMRI in 91 subjects during an interference task (color-word Stroop) and during a planning task (Tower of London; ToL). We found that both Stroop interference and ToL planning significantly increased heart rate in the scanner and confirmed significant main effects of heart rate regressors on the fMRI signals. Nevertheless, statistical contrasts that test for increased fMRI during Stroop interference and ToL planning were not significantly influenced by inclusion of heart rate regressors. We conclude therefore that fMRI changes associated with heart rate changes do not impact strongly on higher-order fMRI effects in these commonly used executive function tasks, but routinely adding a correction seems prudent.

The pedunculopontine nucleus is related to visual hallucinations in Parkinson's disease: preliminary results of a voxel-based morphometry study.

Visual hallucinations (VH) are common in Parkinson's disease (PD) and lead to a poor quality of life. For a long time, dopaminergic therapy was considered to be the most important risk factor for the development of VH in PD. Recently, the cholinergic system, including the pedunculopontine nucleus (PPN), has been implicated in the pathophysiology of VH. The aim of the present study was to investigate grey matter density of the PPN region and one of its projection areas, the thalamus. Thirteen non-demented PD patients with VH were compared to 16 non-demented PD patients without VH, 13 demented PD patients (PDD) with VH and 11 patients with dementia with Lewy bodies (DLB). Isotropic 3-D T1-weighted MRI images (3T) were analysed using voxel-based morphometry (VBM) with the PPN region and thalamus as ROIs. PD and PDD patients with VH showed grey matter reductions of the PPN region and the thalamus compared to PD patients without VH. VH in PD(D) patients are associated with atrophy of the PPN region and its thalamic target area, suggesting that a cholinergic deficit may be involved in the development of VH in PD(D).

Neuroimaging of response interference in twins concordant or discordant for inattention and hyperactivity symptoms.

Attention deficit hyperactivity disorder (ADHD) is to a large extent influenced by genetic factors, but environmental influences are considered important as well. To distinguish between functional brain changes underlying primarily genetically and environmentally mediated ADHD, we used functional magnetic resonance imaging (fMRI) to compare response interference in monozygotic twins highly concordant or discordant for attention problems (AP). AP scores were assessed longitudinally with the Child Behavior Check List attention problem scale (CBCL-AP). Response interference was measured during two executive function paradigms; a color-word Stroop and a flanker task. The neuroimaging results indicated that, across the entire sample, children with high CBCL-AP scores, relative to children with low CBCL-AP scores, showed decreased activation to response interference in dorsolateral prefrontal, parietal and temporal brain regions. Increased activation was noted in the premotor cortex and regions associated with visual selective attention processing, possibly reflecting compensatory mechanisms to maintain task performance. Specific comparisons of high and low scoring concordant twin pairs suggest that AP of genetic origin was characterized by decreased activation of the left dorsolateral prefrontal cortex during the Stroop task and right parietal lobe during the flanker task. In contrast, comparison of twins from discordant monozygotic pairs, suggests that AP of environmental origin was characterized by decreased activation in left and right temporal lobe areas, but only during Stroop interference. The finding of distinct brain activation changes to response interference in inattention/hyperactivity of "genetic" versus "environmental" origin, indicates that genetic and environmental risk factors for attention/hyperactivity problems affect the brain in different ways.

A structural MRI study in monozygotic twins concordant or discordant for attention/hyperactivity problems: evidence for genetic and environmental heterogeneity in the developing brain.

Several structural brain abnormalities have been reported in patients with Attention Deficit Hyperactivity Disorder (ADHD). However, the etiology of these brain changes is still unclear. To investigate genetic and environmental influences on ADHD related neurobiological changes, we performed Voxel-Based Morphometry on MRI scans from monozygotic (MZ) twins selected from a large longitudinal population database to be highly concordant or highly discordant for ratings on the Child Behavior Checklist Attention Problem scale (CBCL-AP). Children scoring low on the CBCL-AP are at low risk for ADHD, whereas children scoring high on this scale are at high-risk for ADHD. Brain differences between concordant high-risk twin pairs and concordant low-risk twin pairs likely reflect the genetic risk for ADHD; brain differences between the low-risk and high-risk twins from discordant MZ twin pairs reflect the environmental risk for ADHD. A major difference between comparisons of high and low-risk twins from concordant pairs and high/low twins from discordant pairs was found for the prefrontal lobes. The concordant high-risk pairs showed volume loss in orbitofrontal subdivisions. High-risk members from the discordant twin pairs exhibited volume reduction in the right inferior dorsolateral prefontal cortex. In addition, the posterior corpus callosum was compromised in concordant high-risk pairs, only. Our findings indicate that inattention and hyperactivity symptoms are associated with anatomical abnormalities of a distributed action-attentional network. Different brain areas of this network appear to be affected in inattention/hyperactivity caused by genetic (i.e., high concordant MZ pairs) vs. environmental (i.e., high-low discordant MZ pairs) risk factors. These results provide clues that further our understanding of brain alterations in ADHD.

Inter-hemispheric lateralization of event related potentials; motoric versus non-motoric cortical activity.

To study hemispheric lateralization of cortical potentials associated with motoric and non-motoric function, cortical activity was recorded accompanying either finger extension or saccadic eye movements in a contingent negative variation (CNV) paradigm. Subjects viewed computer-generated pacing stimuli, presented in the left visual hemi-field, and were instructed to either initiate or inhibit a motor response following an imperative signal. Motoric lateralization was assessed by means of the lateralized readiness potential (LRP). In addition, a measure complementary to the LRP was introduced to investigate non-motoric lateralization (NML). Contralateral inter-hemispheric lateralization was evident in the LRP preceding finger movement, but was absent prior to eye movements. However, pre-saccadic cortical response profiles did exhibit a right hemispheric, non-motoric lateralization (NML) during stimulus presentation. Comparable non-motoric lateralization was found for finger extension. Results of the present study suggest that non-motoric lateralization may be a contributing factor to the frequently reported inter-hemispheric asymmetry preceding self-initiated saccadic eye movements. Results of the present study also suggest that the latter may be related to a covert shift of visuospatial attention toward the saccadic target. Associated shifts of attention are suppressed in a CNV paradigm, where attentional focus is primarily on the CNV stimulus during the pre-saccade period.