Working memory (WM) is a cognitive process that refers to storing information in a temporary system that allows monitoring and handling this information.

To propose and validate a new fMRI paradigm to study WM and its neuroanatomical substrates, using a language-free adaptation of the 2-back working memory task in order to avoid cultural and educational bias.

To test the hypothesis that the proposed paradigm would produce an increase of the BOLD signal in specialized areas for spatial WM (Superior Frontal Sulcus) and areas for monitoring and handling this information (Dorsolateral Prefrontal Cortex) in healthy participants. We also expected a significantly higher behavioral performance in this group than in subjects with suspected WM impairment due to acquired brain injury.

10 neurologically healthy participants and 11 ABI participants performed the task in a block design experiment with four runs. These observed a 9-square matrix with one of the squares painted black and pressed a button each time the black square was the same as the one two trials back. We analyzed behavioral performance and brain activation in repeated trials.

Higher BOLD activation of brain regions was associated with the performance of the WM task in the healthy group, as well as better behavioral performance. We also present behavior results of both groups, so these data can be compared to other clinical groups with suspected WM deficits.

This task may be used as a research methodology for behavioral and neuroimaging studies of visual WM in block-design paradigms.

The evidence of 5-HTTLPR effects on resting state amygdala activity is inconsistent. Investigators reported either enhanced perfusion in 5-HTTLPR short allele carriers or no genetic effect. Gender-related differences in cerebral blood flow (CBF) have been also reported. In this study we tested the hypothesis that the interaction of 5-HTTLPR gene with gender will affect the CBF in amygdala.

To explore the modulation of the amygdala perfusion by gender and 5-HTTLPR polymorphisms.

We recruited 81 right-handed white Caucasian healthy volunteers (42 females) aged 19–55 years. Resting CBF was examined using a pseudo-continuous arterial spin labelling technique. The BOLD signal to dynamic facial expressions was acquired to determine the amygdala activation. All participants were genotyped for the 5-HTTLPR gene (ll-ls-ss alleles and La-Lg variants).

We found a significant main effect of gender in left (p = 0.006) and right (p < 0.001) amygdalas, with higher CBF in males. An interaction between gender and 5-HTTLPR was significant in right amgydala (p = 0.008). This was accounted for by higher values of CBF in right amygdala in male s allele carriers compared with females. In the females only, the BOLD response to facial emotions significantly and negatively correlated with CBF in right amygdala.

The novelty of our results is in the demonstration of gene by gender interaction that might help to interpret some of the inconsistencies in existing literature. We suggest that CBF measure provides for an indirect estimate of susceptibility to emotional signals.

Minor motor and sensory deficits or neurological soft signs (NSS) are frequently found in patients with schizophrenia at any stage of their illness. Numerous structural magnetic resonance imaging (MRI) studies repeatedly revealed accentuated thinning of cortical mantle in schizophrenia. However, whether NSS are related to alterations of cortical thickness has so far remained mostly unexplored.

Whole brain high-resolution MRI at 3 Tesla was used to investigate cortical thickness in twenty five patients with recent-onset schizophrenia. Cortical reconstruction was performed with the Freesurfer image analysis suite. NSS were examined on the Heidelberg Scale after remission of acute symptoms and related to cortical thickness. Age, education, medication and duration of illness were considered as potential confounders.

Higher NSS scores were associated with decreased cortical thickness in multiple areas. Significant correlations were found in somatosensory and primary motor cortex, pre-motor area and temporal lobe. Our results confirm the hypothesis of significant relationship between alterations of cortical thickness and the extent of NSS in schizophrenia.

Our findings provide new insights into the association of NSS with brain morphometric alterations and an involvement of cortical thickness in schizophrenia.

Functional magnetic resonance imaging (fMRI) studies in schizophrenia found altered brain activation patterns during Theory of Mind (ToM) task performance in the so-called ToM-network, recently focusing on over- rather than under-activation. Even though most fMRI-studies applied tasks that might gradually activate the ToM-network, no study so far has investigated the time-course of ToM-performance. Some of the varying activation results might thus be due to time-course of performance.

Our aim was to investigate neural activation over time in schizophrenia compared with a healthy control sample.

Using a block design in fMRI, we presented a sophisticated paradigm that depicts moving geometrical shapes interacting in social patterns. 14 patients with schizophrenia and 15 healthy controls participated in the study. Functional activation patterns were investigated for the first and second half of the videos separately.

Both groups activated brain areas related to the ToM-network during performance of ToM videos as compared to a baseline condition. Most importanly, schizophrenia patients showed activation in ToM-related brain areas only in the second part, while healthy controls activated the ToM-network in the first part of the video presentation.

Results confirm recent findings of an increased activation in ToM-related brain areas in schizophrenia. Moreover, patients activated ToM-related brain areas later than healthy controls. This delay might be due to a general cognitive slowing, symptom-related inhibition of cognition-associated processes or specific delay in task processing. As this is the first study to investigate this time-course of ToM, more research is needed to classify results.

Depressed patients demonstrate low frustration tolerance which increases the risk of suicide and causes difficulties in social adaptation. Resting-state neuroimaging studies revealed abnormalities in “default-mode” network in Major Depressive Disorder (MDD). To our knowledge, functional network responsible for frustration has not been investigated in depressed subjects previously.

To investigate functional responses to frustration in MDD subjects and healthy controls (HCs).

15 subjects with MDD and 15 HCs underwent 10-min fMRI scanning. We used modified Stroop-test to investigate subjects’ responses to frustration. There were two sessions: during the first one the subject had to determine the color of the text by pressing corresponding button while scanning; the second one was a “frustrative” part when the subject had to respond within a short period of time. We modified this interval so that it was almost impossible to respond correctly and keep within the allotted time. The subject was being informed on its performance during the test. Independent component analysis was used to isolate the frustration network in each subject. Group maps of the response network were compared. A within-group analysis was performed in the MDD group to explore effects of depression scores on functional connectivity.

We revealed differences in limbic functional connectivity patterns during the test perfomance in MDD in comparison to HCs.

The findings suggest that low frustration tolerance in depressed patients can be explained by the impaired function of stress-response brain network and reveal perspectives for future research on depression and suicide risk.

Conduct disorder (CD) may be associated with problems in understanding the thoughts and intentions of others. These abilities include mentalizing skills and are important for successful social interactions. Previous neuroimaging studies have that mentalizing is consistently associated with activation of a set of specific brain regions.

To identify potential abnormalities of the social brain during mentalizing in adolescents suffering from CD.

A group of 14 adolescents with CD and a sex- and age-matched group of 16 adolescents without mental disorders were scanned with functional MRI during watching simple animations of two triangles that moved either randomly or in way that implied intentional movements and interactions (Theory of Mind (ToM) animations). SPM8 was used for data preprocessing and statistical analysis,

In both groups, ToM animations led to increased activation in core regions of the social brain (temporal, temporoparietal, occipitotemporal and medial frontal regions). In the right temporoparietal cortex, these increased activation in response to ToM animations were reduced in the CD group compared to the control group.

The right temporoparietal cortex a core region of the mentalizing brain showed reduced activation in adolescents with CD. This result suggests that CD is associated with a dysfucntion in the neural processing of social information

Depression is common in Alzheimer's disease (AD) with important clinical implications, but the etiology is not known.

30 subjects (15 with depression and 15 non-depressed matched for age, gender and cognitive impairment) with mild probable AD, defined as Mini-Mental State Examination score of 20 or above, diagnosed according to NINCDS-ADRDA criteria were included in the study. Data were collected at geriatric medicine and psychiatry outpatient clinics at three hospitals in Western Norway and all subjects underwent comprehensive clinical assessment. Montgomery-Asberg Depression Rating Scale with a cut-off point of 6/7 was used to evaluate depression. Automatic preprocessing using Freesurfer included steps for white and grey matter surface reconstruction. The resulting cortical thickness measurement was used in the subsequent GLM-based analysis. Correction for multiple comparisons was carried out cluster-wise by method of Monte Carlo.

We found 3 clusters of significantly reduced cortical thickness in the depressed group. The first cluster (p = 0,0014) contained Left Frontal Pole and Lateral Orbitofrontal cortex. The second cluster (p = 0,0131) included Left Anterior Temporal Area; Right Medial Prefrontal, Anterior Cingulate, Subgenual Cingulate and Medial Orbitofrontal cortex were included in the third cluster (p = 0,0032).

Depression in AD is associated with reduced cortical thickness in prefrontal and anterior temporal cortices. These areas have been found to be associated with depression in other age-related disorders as well as in major depression. This convergence of morphological profiles suggests a possible unity of depression brain mechanisms across disorders.

Functional network disruption in degenerative dementia has been reported. EEG coherence is used to assess functional connectivity between brain areas. Previous studies of Huntington's disease (HD) reported about electroencephalography (EEG) spectral power and source location, but coherence has not yet been examined.

To examine EEG intracortical functional connectivity in HD using low-resolution brain electromagnetic tomography (LORETA).

In 55 HD patients and 55 controls, 3-minute 19-channel vigilance-controlled EEG was recorded, and recomputed to current densities of 6239 cortical sLORETA voxels. These were recomputed into source model time series for 19 regions of interest (ROIs). Coherence overestimation due to volume conduction was avoided by computing functional connectivity as ‘lagged’ coherence. This was done for each ROI pair (19*18/2=171) in each of 8 EEG frequency bands (delta through gamma). Statistics tested coherences (a) HD patients versus controls, and (b) HD patients in early versus late disease stages.

(a) HD patients showed only reduced connectivities compared to controls (p < 0.05 corrected for multiple comparison), involving EEG theta, alpha-1-2 and beta1-2-3 frequency bands. The largest number of reduced connectivities occurred in alpha-1 (79 cases) and beta-2 (96 cases). (b) HD stage-1 versus stage-3-4 revealed only one significant difference.

HD compared to controls showed massive reduction of functional connectivity. This occurred early and remained stable during disease progression. As in other dementing disorders, for example Alzheimer disease, the largest reduction concerned alpha and beta EEG frequencies. The results suggest a neocortical disconnection syndrome of a primarily subcortical disease.

Charles Bonnet syndrome (CBS) is a condition characterized by complex and recurrent visual hallucinations occurring in patients with severe visual loss, in the absence of cognitive or psychiatric disorders. Patients are completely aware of the unrealistic nature of this phenomenon. Previous functional magnetic resonance imaging (fMRI) studies have demonstrated cortical activation during periods of visual hallucinations in patients with CBS pointing to dysfunction in the primary and secondary visual cortices.

To investigate the pattern of visual activation in a patient with CBS by means of resting-state fMRI.

We studied the case of a 75-year-old woman with pronounced visual loss secondary to diabetic retinopathy and recurrent visual hallucinations consistent with CBS. The patient underwent an fMRI examination. No convincing periods of visual hallucinations occurred at the time of scanning. A blood oxygen level dependent (BOLD) sequence (TE = 25 ms, TR = 3000 ms, number of repetitions=200, acquisition matrix=64 × 64) was acquired. After spatial pre-processing including realignment, unwarping, and coregistration to high-resolution T1-weighted images by means of statistical parametric mapping (SPM, FIL, London, UK), BOLD images were analysed by using multivariate exploratory linear optimized decomposition into independent components (MELODIC, FSL, FMRIB, Oxford, UK).

The independent component analysis (ICA) revealed a very extensive visual network, much more pronounced than the usually observed.

fMRI data analysed by using ICA seem to demonstrate abnormal visual networks in CBS, even at “rest”. This perhaps indicates that there is a sustained state of hyperactivity in the primary and secondary visual cortices in CBS, most probably secondary to deafferentiation.

Several diffusion tensor imaging (DTI) studies have shown disturbed white matter integrity in various brain areas in schizophrenia patients compared to controls, while studies investigating the effects of antipsychotics on white matter integrity is scarce, and the effect of clozapine on DTI measures have not yet been studied.

The purpose of this study was to investigate the influence of clozapine on white matter integrity in patients with chronic schizophrenia by using Tract-Based-Spatial-Statistics (TBSS).

DTI of sixteen patients with schizophrenia (M/F: 10/6) were performed before the initiation, and at 3rd month of clozapine treatment using a 1.5 T MR scanner (Magnetom TIM, Siemens, Germany). A voxelwise statistical analysis of fractional anisotropy (FA) maps was carried out using TBSS, part of the FSL software package. Voxelwise statistics on the skeletonised FA data was computed at a threshold level of p < 0.05. White matter structures with significant group differences in FA were extracted as ROIs, registered to and overlaid onto an anatomical template and labelled using the MRI Atlas of Human White Matter.

TBSS-DTI revealed significant increases in FA after 3 months of clozapine administration in bilateral, but predominantly right hippocampus, genu and splenium of the corpus callosum, fornices, frontal, parietal and temporal white matter.

To our knowledge this is the first study to show that clozapine treatment resulted in a widespread increase in FA, indicative of improved white matter integrity. Clozapine may exert its effects by improving intra- and interhemispheric connectivity among cortical and subcortical regions.

Bipolar Disorder (BD) is a chronic mood disorder with a prevalence estimated around 1–2%. Bipolar patients may experience social and working residual impairment even during euthymia. Furthermore, specific cognitive deficits, particularly involving working memory (WM), may persist during eythymia as well.

To evaluate the possible presence of cognitive and functional differences between euthymic bipolar subjects vs. healthy controls during euthymia by means of a WM task at fMRI associated with neuropsychological evaluations.

A sample of 30 subjects aged between 20 and 45 years (15 with BD and 15 controls) underwent fMRI examination at 3 Tesla with tasks of working memory (n-back). All participants received a neuropsychological evaluation, inlcuding Stroop Color-Word Interference test, Tower of London, Trail Making Test, Wisconsin Card Sorting Test and Verbal Fluency Test. Comparison tests were performed using statistical software SPSS and SPM5.

The performance of the control group was significantly higher than both at the n-back task and at the neuropsychological tests. The full-factorial analysis of fMRI data showed a hypoactivation in bipolar patients in particular hippocampus and thalamus, associated with increased involvement of areas not involved in the frontal-parietal networks classically associated with WM.

The results seem to confirm the existence of a residual dysfunction during euthymia phase in BD, suggesting two distinct patterns of activation in the two groups studied, both from a neuropsychological point of view and from a neuroimaging perspective.

Serotonin (5-HT) is thought to be critical for affect regulation in the brain and many antidepressants are thought to primarily work by altering 5-HT levels. However there has not been a validated means of directly imaging of endogenous 5-HT levels in humans. The main aims of this project are to image the effect of Citalopram on brain endogenous 5-HT levels and to determine the relationship between brain 5-HT and affect regulation.

Thirteen healthy volunteers (mean age 50.9yrs, range 35–63) underwent two Positron Emission Tomography (PET) scans with [11C]-CUMI, a highly selective 5-HT1A agonist radioligand. Subjects received either a slow intravenous infusion of citalopram 10mg or saline starting 45 minutes before each PET scan in a randomized design. All subjects had a functional MRI emotion processing task (block design) known to activate the amygdala on a separate day.

The citalopram infusion induced 6–11% increases in [11C]-CUMI binding potential in anterior cingulate, insula and cortical brain regions (p < 0.05 corrected for repeated measures).

BOLD response to fearful vs neutral faces in the left amygdala inversely correlated with baseline dorsal raphe BP (Pearson r2 =−0.90, p < 0.001) and directly correlated with dorsal raphe BP changes (r2=0.51, p = 0.07).

The increase in [11C]CUMI-101 availability would be consistent with a decrease in endogenous 5-HT availability in certain terminal regions. The relationship between brain emotion processing and [11C]-CUMI binding in the raphe indicates the 5-HT levels at presynaptic receptors regulate emotional processing and suggests presynaptic 5-HT as a treatment target for affective disorders.

Mounting evidence has implicated oxidative stress in severe psychiatric disorders, including major depressive disorder (MDD). Glutathione (GSH) is the major intracellular antioxidant that protects cells against oxidative stress.

To test the hypothesis that oxidative stress is implicated MDD by measuring cortical GSH in MDD patients and in matched healthy controls in vivo, using magnetic resonance spectroscopy (MRS).

Fifteen psychotropic medication-free patients with MDD diagnosed according DSM-IV-TR criteria and 13 healthy volunteers (HV) participated in the study. A history of other axis I diagnoses or substance/alcohol abuse was exclusionary for all subjects. In vivo brain GSH levels, expressed in institutional units, were obtained from a single 3 × 3 × 2-cm3 occipital lobe voxel at 3.0 Tesla using MRS spectral editing.

Statistical comparisons revealed a 20.6% mean cortical GSH decrease (p< .003) in MDD (2.3 ± 0.4) compared to HV (2.9 ± 0.6), which remained significant after adjusting for age, sex, bmi, and smoking status. In addition, we found GSH levels to correlate negatively with depressive symptoms and with indices of emotional and functional disability across all participants.

To our knowledge, this is the first study to report a significant cortical GSH deficit in vivo in MDD, a finding that supports a role for oxidative stress in the pathophysiology of the disorder, and suggests the viability of treatment strategies based on using synthetic GSH precursors, such as N-acetylcysteine, to spur in situ synthesis and elevation of the antioxidant and mitigate the pathogenic effects of oxidative stress.

Imaging genetic studies provide for the possibility to uncover endophenotypes for neuropsychiatric disorders.

To establish neuroimaging correlates of the joint effect of serotonergic (5-HTTLPR) and dopaminergic (COMT) genes.

To examine an interaction of 5-HTTLPR and COMT markers on effective connectivity and regional brain volume in healthy individuals.

Ninety one healthy Caucasian adults underwent functional magnetic resonance imaging (fMRI) and structural MRI. In fMRI study the participants were presented with videoclips of dynamic emotional facial expressions of fear, sadness, happiness and anger. The effective connectivity within the emotion processing circuitry was assessed with Granger causality method. In the structural neuroimaging part of the study we applied diffeomorphic anatomic registration through exponentiated Lie algebra (DARTEL) whole-brain voxel-based morphometry (VBM).

In fear processing condition, an interaction between 5-HTTLPR (S) and COMT(met) low activity alleles was associated with reduced effective connectivity within the facial emotion processing circuitry.

The results of the structural data analysis showed an interaction of COMT and 5-HTTLPR genotypes with regional grey matter volume in bilateral parahippocampal gyrus, amygdala, hippocampus, cerebellum and right putamen. In particular, the gray matter volume in these regions was smaller in individuals who were both COMT-met and 5-HTTLPR-S carriers, as compared to those carrying either 5-HTTLPR-L/L, or COMT-val/val.

The epistatic effect of COMT-met and 5-HTTLPR-S markers impacts on both the brain function and structure and may underlie an inefficient emotion regulation.