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One of the major risk factors for global death and disability is alcohol, tobacco, and illicit drug use. While there is increasing knowledge with respect to individual factors promoting the initiation and maintenance of substance use disorders (SUDs), disease trajectories involved in losing and regaining control over drug intake (ReCoDe) are still not well described. Our newly formed German Collaborative Research Centre (CRC) on ReCoDe has an interdisciplinary approach funded by the German Research Foundation (DFG) with a 12-year perspective. The main goals of our research consortium are (i) to identify triggers and modifying factors that longitudinally modulate the trajectories of losing and regaining control over drug consumption in real life, (ii) to study underlying behavioral, cognitive, and neurobiological mechanisms, and (iii) to implicate mechanism-based interventions. These goals will be achieved by: (i) using mobile health (m-health) tools to longitudinally monitor the effects of triggers (drug cues, stressors, and priming doses) and modify factors (eg, age, gender, physical activity, and cognitive control) on drug consumption patterns in real-life conditions and in animal models of addiction; (ii) the identification and computational modeling of key mechanisms mediating the effects of such triggers and modifying factors on goal-directed, habitual, and compulsive aspects of behavior from human studies and animal models; and (iii) developing and testing interventions that specifically target the underlying mechanisms for regaining control over drug intake.

Impaired neural plasticity may be a core pathophysiological process underlying the symptomatology of schizophrenia. Plasticity-enhancing interventions, including repetitive transcranial magnetic stimulation (rTMS), may improve difficult-to-treat symptoms; however, efficacy in large clinical trials appears limited. The high variability of rTMS-related treatment response may be related to a comparably large variation in the ability to generate plastic neural changes. The aim of the present study was to determine whether negative symptom improvement in schizophrenia patients receiving rTMS to the left dorsolateral prefrontal cortex (DLPFC) was related to rTMS-related brain volume changes. A total of 73 schizophrenia patients with predominant negative symptoms were randomized to an active (n=34) or sham (n=39) 10-Hz rTMS intervention applied 5 days per week for 3 weeks to the left DLPFC. Local brain volume changes measured by deformation-based morphometry were correlated with changes in negative symptom severity using a repeated-measures analysis of covariance design. Volume gains in the left hippocampal, parahippocampal and precuneal cortices predicted negative symptom improvement in the active rTMS group (all r⩽-0.441, all P⩽0.009), but not the sham rTMS group (all r⩽0.211, all P⩾0.198). Further analyses comparing negative symptom responders (⩾20% improvement) and non-responders supported the primary analysis, again only in the active rTMS group (F(9, 207)=2.72, P=0.005, partial η 2=0.106). Heterogeneity in clinical response of negative symptoms in schizophrenia to prefrontal high-frequency rTMS may be related to variability in capacity for structural plasticity, particularly in the left hippocampal region and the precuneus.

Objective At the present, it is unclear whether association of basal forebrain cholinergic system (BFCS) volume with cognitive performance exists in healthy as well as in cognitively impaired elderly subjects. Whereas one small study reported an association of BFCS volume with general cognitive ability ‘g’ in healthy ageing, effects on specific cognitive domains have only been found in subjects with cognitive decline. Here we aim to clarify whether an association of BFCS volume and ‘g’ is present in a larger sample of elderly subjects without obvious symptoms of dementia and whether similar associations can also be observed in specific cognitive domains. Methods 282 pre-surgical patients from the BioCog study (aged 72.7 ± 4.9 years with a range of 65–87 years, 110 women) with a median MMSE score of 29 points (range 24–30) were investigated. BFCS and brain volume as well as brain parenchymal fraction were assessed in T1-weighted MR images using SPM12 and a probabilistic map of the BFCS. Neuropsychological assessment comprised the CANTAB cognitive battery and paper-and-pencil based tests. For data analysis, generalised linear models and quantile regression were applied. Results Significant associations of BFCS volume with ‘g’ and several cognitive domains were found, with the strongest association found for ‘g’. BFCS volume explained less variance in cognitive performance than brain volume. The association was not confounded by brain parenchymal fraction. Furthermore, the association of BFCS volume and ‘g’ was similar in high- and low-performers. Conclusion Our results extend previous study findings on BFCS volume associations with cognition in elderly subjects. Despite the observed associations of BFCS volume and cognitive performance, this association seems to reflect a more general association of brain volume and cognition. Accordingly, a specific association of BFCS volume and cognition in non-demented elderly subjects is questionable.

Decisions are called decisions under uncertainty when either prior information is incomplete or the outcomes of the decision are unclear. Alterations in these processes related to decisions under uncertainty have been linked to delusions. In patients with schizophrenia, the underlying neural networks have only rarely been studied. We aimed to disentangle the neural correlates of decision-making and relate them to neuropsychological and psychopathological parameters in a large sample of patients with schizophrenia and healthy subjects. Fifty-seven patients and fifty-seven healthy volunteers from six centers had to either indicate via button-press from which of two bottles red or blue balls were drawn (decision-making under uncertainty condition), or indicate whether eight red balls had been presented (baseline condition) while BOLD signal was measured with fMRI. Patients based their decisions on less conclusive evidence and had decreased activations in the underlying neural network, comprising of medial and lateral frontal as well as parietal areas, as compared to healthy subjects. While current psychopathology was not correlated with brain activation, positive symptoms led to longer decision latencies in patients. These results suggest that decision-making under uncertainty in schizophrenia is affected by a complex interplay of aberrant neural activation. Furthermore, reduced neuropsychological functioning in patients was related to impaired decision-making and task performance was modulated by distinct positive symptoms.

Objective In parametric fMRI studies the relationship between the amplitude of the hemodynamic response and electrophysiological or behavioral parameters is commonly analyzed using the general linear model (GLM). We examined ways of using single-trial response time (RT) in the analysis of a decision-making task to better isolate task-specific activation. Methods fMRI and RT data were recorded in twenty-one subjects performing a visual-oddball-task. Four explanatory variables (EVs) were generated for the GLM-analysis: A conventional (constant impulse) EV, a constant epoch EV informed using subjects’ average RT, a variable impulse EV and a variable epoch EV both informed using single-trial RT. EVs were tested individually and as orthogonalized pairs. Results The individual EVs all detected similar extensive patterns of activation, while orthogonalized EVs were mainly correlated with BOLD signal variance in sensorimotor and parietal areas. Orthogonalizing the variable epoch EV to the constant epoch EV isolated cortical regions resembling the “dorsal frontoparietal attention network” from activation detected by the conventional (i.e., constant impulse) analysis. Conclusion For short event durations, the activation detected by individual EVs is very similar, but orthogonalized, parametrically informed EVs can improve isolation of task-specific BOLD signal change. Significance Different approaches for integrating parametric timing measures in fMRI analyses can significantly influence outcomes, refining or confounding findings.

Attributions are constantly assigned in everyday life. A well-known phenomenon is the self-serving bias: that is, people's tendency to attribute positive events to internal causes (themselves) and negative events to external causes (other persons/circumstances). Here, we investigated the neural correlates of the cognitive processes implicated in self-serving attributions using social situations that differed in their emotional saliences. We administered an attributional bias task during fMRI scanning in a large sample of healthy subjects (n = 71). Eighty sentences describing positive or negative social situations were presented, and subjects decided via buttonpress whether the situation had been caused by themselves or by the other person involved. Comparing positive with negative sentences revealed activations of the bilateral posterior cingulate cortex (PCC). Self-attribution correlated with activation of the posterior portion of the precuneus. However, self-attributed positive versus negative sentences showed activation of the anterior portion of the precuneus, and self-attributed negative versus positive sentences demonstrated activation of the bilateral insular cortex. All significant activations were reported with a statistical threshold of p ≤ .001, uncorrected. In addition, a comparison of our fMRI task with data from the Internal, Personal and Situational Attributions Questionnaire, Revised German Version, demonstrated convergent validity. Our findings suggest that the precuneus and the PCC are involved in the evaluation of social events with particular regional specificities: The PCC is activated during emotional evaluation, the posterior precuneus during attributional evaluation, and the anterior precuneus during self-serving processes. Furthermore, we assume that insula activation is a correlate of awareness of personal agency in negative situations.

In this multicenter, double-blind, placebo-controlled, randomized, four way cross-over proof-of-mechanism study, we tested the effect of the positive allosteric α7 nicotinic acetylcholine receptor (nAChR) modulator JNJ-39393406 in a key translational assay (sensory P50 gating) in 39 regularly smoking male patients with schizophrenia. All patients were clinically stable and JNJ-39393406 was administered as an adjunct treatment to antipsychotics. No indication was found that JNJ-39393406 has the potential to reverse basic deficits of information processing in schizophrenia (sensory P50 gating) or has a significant effect on other tested electrophysiological markers (MMN, P300 and quantitative resting EEG). Sensitivity analyses including severity of disease, baseline P50 gating, medication and gene variants of the CHRNA7 gene did not reveal any subgroups with consistent significant effects. It is discussed that potential positive effects in subgroups not present or not large enough in the current study or upon chronic dosing are possible, but unlikely to be developed. This article is part of a Special Issue entitled ‘Cognitive Enhancers’.

Brain and behavior 6(1), e00421 (2016). doi:10.1002/brb3.421, Published by Wiley, Malden, Mass.

Nicotine can have beneficial effects on attention performance and corresponding brain function in both schizophrenia patients and healthy controls, but it remains controversial whether nicotine affects brain function differentially in patients vs. controls. The effects of nicotine on brain activity elicited by attention-requiring oddball-type tasks have not been studied in schizophrenia patients. In this study we sought to investigate the impact of nicotine on the p300 evoked potential component and corresponding fMRI (functional magnetic resonance imaging) activation measures in schizophrenia patients and controls. Applying a double-blind, placebo-controlled cross-over design, the effects of 1mg nasal nicotine on brain activity elicited by a visual oddball-type task in N =14 schizophrenia and N =15 control smokers were studied with simultaneous EEG-fMRI. EEG single trial amplitudes were used to inform the fMRI analysis. We found a nicotine-associated increase in P300-informed fMRI activation in schizophrenia patients and controls, mainly in the anterior cingulate and adjacent medial frontal cortex. No group differences in the response to nicotine were found. Remarkably, averaged EEG and fMRI activation measures considered in isolation were largely unaffected by nicotine. Taken together, the effects of nicotine on P300 amplitude-associated brain activation do not seem to be fundamentally different in schizophrenic smokers and healthy controls.

More than 80 % of patients diagnosed with schizophrenia are nicotine-dependent. Self-medication of cognitive deficits and an increased vulnerability to stress are discussed as promoting factors for the development of nicotine dependence. However, the effects of nicotine on social cognition and subjective stress responses in schizophrenia are largely unexplored. A 2 × 2-factorial design (drug × group) was used to investigate the effects of nicotine versus placebo in smoking schizophrenia patients and healthy controls after 24 h of abstinence from smoking. Participants performed a facial affect recognition task and a semi-standardized role-play task, after which social competence and self-reported stress during social interaction were assessed. Data analysis revealed no significant group differences in the facial affect recognition task. During social interaction, healthy controls showed more non-verbal expressions and a lower subjective stress level than schizophrenia patients. There were no significant effects of nicotine in terms of an enhanced recognition of facial affect, more expressive behaviour or reduced subjective stress during social interaction. While schizophrenia patients unexpectedly recognized facial affect not significantly worse than healthy controls, the observed group differences in subjective stress and non-verbal expression during social interaction in the role-play situation are in line with previous findings. Contrary to expectations derived from the self-medication hypothesis, nicotine showed no significant effects on the dependent variables, perhaps because of the dosage used and the delay between the administration of nicotine and the performance of the role-play.

The aim of the present study was to examine neurocognitive function associated with chronic nicotine use. A total of 2163 healthy participants (1002 smokers, 1161 never-smoking controls) participated in a population-based case- control design.The main outcome measures were six cognitive domain factors derived from a neuropsychological test battery. In smokers, the battery was administered after controlled smoking of one cigarette. Analyses included age, sex and education as covariates. Results demonstrated small, but significant deficits in smokers for visual attention (P < 0.001) and cognitive impulsivity (P < 0.006), while verbal episodic memory, verbal fluency, verbal working memory, and Stroop-interference did not differ between groups. These attention/impulsivity deficits were also present in smokers with only a low amount of cigarette consumption. Lifetime nicotine use (pack-years) was not correlated with cognition in smokers. In conclusion, this study confirmed subtle and specific cognitive deficits in non-deprived smokers. The independence of these deficits from consumption intensity may argue for an a priori deficit of some cognitive abilities in smokers. These specific deficits may constitute intermediate phenotypes for genetic research on nicotine use.

Heavy smoking and schizophrenia are diversely associated with nicotinic acetylcholine receptor expression, as was shown for brain and lymphocytes. Most studies so far have not systematically differentiated between schizophrenia smokers and non-smokers and were confined either to in vivo or post-mortem study approaches. In order to avoid variable in vivo influences or post-mortem bias, we used stably transformed B-lymphoblast cultures derived from healthy and schizophrenia subjects stratified for smoking versus non-smoking in order to differentiate these clinical conditions with regard to nicotinic acetylcholine receptor expression and regulation. Receptor quantities were measured using [(3)H]-nicotine and [(3)H]-epibatidine binding. At baseline, [(3)H]-nicotine binding was not statistically different between healthy smokers and never-smokers (1.59 ± 0.73 vs. 1.26 ± 0.91 fmol/10(6) cells), while it was reduced in schizophrenia smokers compared to healthy smokers (1.05 ± 0.69 fmol vs. 1.44 ± 0.84/10(6) cells, P = 0.01). In schizophrenia, baseline [(3)H]-nicotine correlated inversely with higher PANSS negative subscale scores. After long-term nicotine incubation (1 μM), [3H]-nicotine binding increased in the group of schizophrenia smokers only (from 1.05 ± 0.69 to 1.54 ± 0.77 fmol/106 cells, P = 0.013), while [(3)H]-epibatidine binding decreased in this group (4.52 ± 1.52 to 3.82 ± 1.38 fmol/10(6) cells, P = 0.038). Our data are in further support of a decrease of nicotinic acetylcholine receptor expression in schizophrenia linked to negative psychotic symptoms, which may be counter-regulated by nicotine exposure.

Structural cerebral deficiencies in smokers have been well characterized by morphometric investigations focussing on cortical and subcortical structures. Although the role of the cerebellum is increasingly noted in mental and addiction disorders, no reports exist regarding cerebellar alterations in smokers employing a methodology specifically designed to assess the cerebellar morphology. We acquired high-resolution MRI scans from 33 heavy smokers and 22 never-smokers and used a voxel-based morphometry (VBM) approach utilizing the Spatially Unbiased Infratentorial (SUIT) toolbox (Diedrichsen 2006) to provide an optimized and fine-grained exploration of cerebellar structural alterations associated with smoking. Relative to never-smokers, smokers showed significant reductions of grey matter volume in the right cerebellum Crus I. The grey matter volume in Crus I correlated negatively with the amount of nicotine dependence as assessed by means of the Fagerström scale. Since Crus I has been identified as the cognitive division of the cerebellum, the structural deficit may in part mediate cognitive deficits previously reported in smokers. Of note, the dependence-related magnitude of the volume deficit may support the notion that the cerebellum is substantially involved in core mechanisms of drug dependence.

P50 gating is a major functional biomarker in research on schizophrenia and other psychiatric conditions with high smoking prevalence. It is used as endophenotype for studying nicotinic systems genetics and as surrogate endpoint measure for drug development of nicotinic agonists. Surprisingly, little is known about P50 gating in the general population and the relationship to smoking-related characteristics. In this multicenter study at six academic institutions throughout Germany, n = 907 never-smokers (NS

Alpha-synuclein (SNCA) is associated with a range of psychiatric diseases including neurodegeneration, alcohol craving, and depression. It regulates cellular homeostasis by virtue of its ability to interfere in dopaminergic, serotonergic, and noradrenergic pathways. To date, it is unclear whether the previously described association between SNCA and depressive symptomatology is limited to females with eating disorders or whether it could be extended to include healthy individuals. We included 105 women and 108 men. Genetic data and mRNA expression analyses were drawn from peripheral blood and the severity of depressive symptoms was quantified by the Beck's Depression Inventory (BDI). We found a significant association between the NACP-Rep1 length polymorphism and the BDI score (p = 0.004). Moreover, there was a significant gender dimorphism regarding mRNA expression of SNCA (p = 0.011). Our analysis revealed no further association between the In4 polymorphism or between the mRNA expression of SNCA and the BDI score. Since this investigation was limited to healthy individuals, conclusions concerning depression according to ICD-10 or DSM-IV cannot be drawn. The reported results may contribute to a better understanding of the molecular mechanisms linked to depressive symptoms.

The aim of this study was to assess the severity of dependence as a factor affecting the attentional bias of smokers towards smoking-related stimuli and to clarify contradictory results of previous studies. A visual dot probe task was administered to 51 smokers and 41 nonsmokers to assess the attentional bias. Smokers were classified into a group of less severely dependent and a group of more severely dependent smokers according to the Fagerström Test for Nicotine Dependence, the number of cigarettes smoked per day or the CO concentration in the expired air. Nicotine craving was assessed as well. The more severely dependent smokers displayed an attentional bias towards smoking-related stimuli, while smokers with less severe nicotine dependence showed a negative attentional bias which was also observed in nonsmokers. A multiple linear regression indicated that CO concentration was the only significant predictor of attentional bias. In the total group of smokers we found a positive association between attentional bias and craving for the rewarding effects of nicotine. Future studies are warranted to further enhance our understanding of factors that affect attentional bias as appetitive responses towards smoking-related stimuli might be an important target for therapeutic interventions.

Preserved executive functioning (EF) is crucial for daily functioning in the elderly and it appears to predict dementia development. We sought to clarify the role of atrophy-corrected cortical grey matter (GM) volume as a potential brain reserve (BR) marker for EF in the elderly. In total, 206 pre-surgical subjects (72.50 ± 4.95 years; mean MMSE score 28.50) were investigated. EF was primarily assessed using the Trail Making Test B (TMT B). Global/ lobar GM volumes were acquired with T1 MP-RAGE. Adjusting for key covariates including a brain atrophy index (i.e. brain parenchymal fraction), multiple linear regression analysis was used to study associations of GM volumes and TMT B. All GM volumes - most notably of global GM - were significantly associated with TMT B independently of GM atrophy (ß = -0.201 to -0.275, p = 0.001 to 0.012). Using atrophy-corrected GM volume as an estimate of maximal GM size in youth may serve as a BR predictor for cognitive decline in future studies investigating BR in the elderly.

We conducted a randomized, sham-controlled repetitive transcranial magnetic stimulation (rTMS) study in chronic schizophrenia in-patients ( n =35) to evaluate the therapeutic efficacy of 10 Hz stimulation. Patients, who were on stable antipsychotic treatment, were randomly assigned to the active or sham condition. In the active rTMS group, ten sessions with a total of 10,000 stimuli were applied over the left dorsolateral prefrontal cortex at 110% of motor threshold. The sham group received corresponding sham stimulation. Clinical improvement was measured by the Clinical Global Impression scale (primary outcome measure), the Global Assessment of Functioning Scale (GAF) and the Positive and Negative Symptom Scale (PANSS; secondary outcome measures). Between-group comparisons revealed no significant differences in clinical outcome variables. Only a subgroup of patients with pronounced negative symptoms developed some clinical improvement as indicated by significant changes in the GAF-scale. Besides there is some evidence for a more favourable clinical outcome within this subgroup after rTMS in the CGI-S and PANSS negative scale, too. In line with earlier investigations, our results suggest a moderate — potentially clinically relevant — treatment effect of prefrontal 10 Hz rTMS stimulation in chronic patients. However, in our study this beneficial effect was restricted to subjects with pronounced negative symptoms. Clinical trial registration information ClinicalTrial.gov Identifier: NCT00169689, http://www.clinicaltrials.gov.

Inattention and impulsivity are the most prominent clinical features of attention deficit hyperactivity disorder (ADHD) in adulthood. Structural and functional neuroimaging studies of subjects with ADHD have demonstrated abnormalities in several brain areas, including fronto-striatal and fronto-cerebellar networks. Mostly, these studies were based on volumetric measurements and have been conducted in children. We investigated white matter (WM) integrity and correlation with measures of attention and impulsivity in adult patients with ADHD adopting diffusion tensor imaging (DTI). N = 37 (21 males) never-medicated adult patients with ADHD combined subtype and N = 34 (16 males) healthy controls were investigated. ADHD diagnosis (DSM-IV) was assessed with clinical interviews and rating scales, subjects also underwent a large neuropsychological test battery including tests of attention and impulsivity. DTI was acquired, and group differences of fractional anisotropy (FA) and mean diffusivity (MD) as well as correlation analyses with measures of attentional performance and impulsivity were calculated using voxel-based analyses. In adult patients with ADHD, we found reduced FA as well as higher MD bilaterally in orbitomedial prefrontal WM and in the right anterior cingulate bundle, while elevated FA was present bilaterally in temporal WM structures. Measures of attention were correlated with DTI parameters in the right superior longitudinal fasciculus, whereas measures of impulsivity were correlated with FA in right orbitofrontal fibre tracts. This is the first DTI study demonstrating disturbed structural connectivity of the frontal-striatal circuitry in adult patients with ADHD. Moreover, a direct correlation between WM integrity and measures of attention and impulsivity is shown.

Introduction The purpose of this study was to assess tolerability and safety of high-frequency rTMS with regard to cognitive performance when conducted as "add-on" treatment in chronic schizophrenia in-patients (n=32). Methods Patients, who were on stable antipsychotic treatment, were randomly assigned to verum or sham condition (double-blind). In the verum group, ten sessions of 10 Hz rTMS with a total of 10 000 stimuli were applied over the left dorsolateral prefrontal cortex (PFC) at 110% of motor threshold over a period of two weeks. The sham group received corresponding sham stimulation. RTMS effects on cognitive performance were assessed with a neuropsychological test battery consisting of the following tests: trail making test A and B (TMT), Wisconsin card sorting test (WCST), D2 attention task and the "short test of general intelligence" (KAI). Results No statistically significant deterioration of cognitive performance was observed as a result of rTMS treatment. Moreover it was shown that in the verum group patients with a less favourable performance on the WCST at baseline tend to improve after rTMS treatment with regard to psychopathology as opposed to patients in the control group. Discussion The stability of cognitive function suggests good tolerability of rTMS treatment in schizophrenia. The absence of evidence for cognitive deterioration could be due to low and short stimulation parameters.

Repetitive transcranial magnetic stimulation (rTMS) is a tool that enables clinicians and neuroscientists to modulate cortical activity in a non-invasive way. High-frequency rTMS has predominantly an activating effect on the stimulated brain region while low-frequency rTMS has an inhibitory effect. In addition to its usefulness as a research tool and in neurological diagnostics, rTMS may prove useful as a therapeutic option in psychiatry, especially in disorders that are associated with regional changes in cortical activity. For instance, rTMS is under current investigation in the treatment of depression and negative symptoms of schizophrenia. A hypofrontality or a fronto-limbic imbalance associated with both syndromes could be corrected by activating, high frequency rTMS. Conversely, a regional hyperactivity in the temporo-parietal cortex has been described in subjects suffering from auditory hallucinations and tinnitus. Low frequency, inhibitory rTMS is currently evaluated as a therapeutic option in these subjects. In addition to the effects on the directly stimulated brain area, other biological effects of rTMS may exert a beneficial influence on brain function. Amongst these are a modulation of cortico-cortical circuits (e. g. fronto-cingular and fronto-parietotemporal circuits), effects on monoaminergic neuromodulation and neuroendocrine effects. The current knowledge about the therapeutically relevant neurophysiological and neuroendocrine effects of rTMS are reviewed. An improved understanding of the neurophysiological basis of the therapeutic effects of rTMS and of the pathophysiology underlying neuropsychiatric diseases may lead to optimized therapeutic rTMS applications and new clinical indications for rTMS.

Objective The study objective is to evaluate the use of qEEG data for the cross-sectional differentiation of mild cognitive impairment (MCI) from mild Alzheimer's disease (AD) and in the longitudinal prediction of cognitive decline in MCI. Methods Eighty-eight subjects with MCI and 42 subjects with mild probable AD were enrolled. Baseline EEGs were recorded using a 32-channel system with electrode positioning according to the international 10–20 system. Digitalized EEG data were further studied by quantitative spectral analysis. Study subjects were followed up for 1 year and reassessed psychometrically. An increase of the total ADAS-cog score of ≥ 4 points was regarded as a significant cognitive decline. Using this cut-off, MCI subjects were sub-grouped into stable MCI (s-MCI) and progressing MCI (p-MCI). Results AD subjects and p-MCI subjects were differentiated from s-MCI subjects by a reduction of alpha power over posterior leads. Reduction of alpha power and mean frequency were significantly correlated with poorer cognitive performance in psychometric tests. Baseline values of alpha power over posterior leads had the highest positive predictive power for MCI and AD (69–80%) and predicted cognitive decline in MCI within a 1-year follow up. Conclusions qEEG revealed decreased alpha activity in progressing MCI and mild AD prior to an increase of slow wave activity, which typically occurs in advancing AD. This finding may reflect an affection of thalamo-cortical relay activity and cortical connectivity in the early disease course of AD. Reduced alpha activity in MCI subjects at baseline may have prognostic value regarding future cognitive decline. Copyright © 2008 John Wiley & Sons, Ltd.

Animal data suggest that the gene neuregulin-1 (NRG1) is involved in neuronal myelination. A haplotype (deCODE) in the 5' end region of the gene was described to double the risk for schizophrenia in an Icelandic population (Stefansson, H., Sigurdsson, E., Steinthorsdottir, V., Bjornsdottir, S., Sigmundsson, T., Ghosh, S., Brynjolfsson, J., Gunnarsdottir, S., Ivarsson, O., Chou, T.T., Hjaltason, O., Birgisdottir, B., Jonsson, H., Gudnadottir, V.G., Gudmundsdottir, E., Bjornsson, A., Ingvarsson, B., Ingason, A., Sigfusson, S., Hardardottir, H., Harvey, R.P., Lai, D., Zhou, M., Brunner, D., Mutel, V., Gonzalo, A., Lemke, G., Sainz, J., Johannesson, G., Andresson, T., Gudbjartsson, D., Manolescu, A., Frigge, M.L., Gurney, M.E., Kong, A., Gulcher, J.R., Petursson, H., Stefansson, K. 2002. Neuregulin-1 and susceptibility to schizophrenia. Am. J. Hum. Genet. 71, 877-892). Of note, there is now increasing evidence of disturbed myelination in this illness--particularly in subcortical frontal lobe white matter (Konrad, A., Winterer, G. 2008. Disturbed structural connectivity in schizophrenia--primary factor in pathology or epiphenomenon? Schiz. Bull. [Electronic publication ahead of print]). Therefore, we investigated with diffusion tensor imaging (DTI) the impact of a tagging single nucleotide polymorphism (SNP) from the deCODE haplotype, i.e., SNP8NRG221533, on fractional anisotropy (FA), which reflects structural integrity of white matter. SNP8NRG221533 was selected because it gave the single best uncorrected association with schizophrenia in the original report by Stefansson et al. (Stefansson, H., Sigurdsson, E., Steinthorsdottir, V., Bjornsdottir, S., Sigmundsson, T., Ghosh, S., Brynjolfsson, J., Gunnarsdottir, S., Ivarsson, O., Chou, T.T., Hjaltason, O., Birgisdottir, B., Jonsson, H., Gudnadottir, V.G., Gudmundsdottir, E., Bjornsson, A., Ingvarsson, B., Ingason, A., Sigfusson, S., Hardardottir, H., Harvey, R.P., Lai, D., Zhou, M., Brunner, D., Mutel, V., Gonzalo, A., Lemke, G., Sainz, J., Johannesson, G., Andresson, T., Gudbjartsson, D., Manolescu, A., Frigge, M.L., Gurney, M.E., Kong, A., Gulcher, J.R., Petursson, H., Stefansson, K. 2002. Neuregulin-1 and susceptibility to schizophrenia. Am. J. Hum. Genet. 71, 877-892). As predicted, we found medial frontal FA to be significantly associated with this NRG1 gene variation. Using voxel-based morphometry (VBM), we could largely exclude the possibility that this genotype effect is indirectly caused by genotype-dependent effects on brain volume. This is the first demonstration that SNP8NRG221533 of the NRG1 gene affects medial frontal white matter microstructure in humans. As the degree of neuronal myelination contributes to structural integrity, our finding further supports a potential role of NRG1 in neuronal myelination in the human brain. By extension, our findings suggest that SNP8NRG221533 may contribute to the risk for the complex polygenic illness schizophrenia via its impact on myelination in frontal lobe white matter.

Objective: This research sought neurobiological features common to psychotic states displayed by patients with different clinical diagnoses. Method: Cluster analysis with quantitative electroencephalographic (QEEG) variables was used to subtype drug-naive, non-medicated, and medicated schizophrenic, depressed and alcoholic patients with psychotic symptoms, from the USA and Germany. QEEG source localization brain images were computed for each cluster. Results: Psychotic patients with schizophrenia, depression and alcoholism, and drug- naive schizophrenic patients, were distributed among six clusters. QEEG images revealed one set of brain regions differentially upregulated in each cluster and another group of structures downregulated in the same way in every cluster. Conclusion: Subtypes previously found among 94 schizophrenic patients were replicated in a sample of 390 non-schizophrenic as well as schizophrenic psychotics, and displayed common neurobiological abnormalities. Collaborative longitudinal studies using these economical methods might improve differential understanding and treatment of patients based upon these features rather than clinical symptoms.

Functional magnetic resonance imaging (fMRI) depends on the coupling of cerebral blood flow, energy demand, and neural activity. The precise nature of this interaction, however, is poorly understood. A positive correlation between BOLD‐response and cortically generated local field potentials, which reflect the weighted average of synchronized dentrosomatic components of pyramidal synaptic signals, has been demonstrated. Likewise, positive BOLD‐responses have been reported in conjunction with scalp‐recorded synchronized electromagnetic activity by a number of groups. However, it is not yet clear how the opposite electromagnetic pattern, i.e. cortical desynchronization, is related to the BOLD signal. To address this question, we conducted a combined event‐related fMRI and 275 sensor whole‐head MEG study during identical visual two‐choice reaction time task conditions in 10 human subjects. We found complex sequences of MEG‐synchronization and desynchronization across a wide frequency range in the visual and motor area in close correspondence with “locales” of positive BOLD‐responses. These results indicate that a correspondence of positive BOLD‐responses is not exclusively found for cortical synchronization but also for desynchronization, suggesting that the relationship between BOLD signals and electromagnetic activity might be more complex than previously thought. Hum Brain Mapp 2006. © 2006 Wiley‐Liss, Inc.

Background Investigators are urgently searching for options to treat negative symptoms in schizophrenia because these symptoms are disabling and do not respond adequately to antipsychotic or psychosocial treatment. Meta-analyses based on small proof-of-principle trials suggest efficacy of repetitive transcranial magnetic stimulation (rTMS) for the treatment of negative symptoms and call for adequately powered multicenter trials. This study evaluated the efficacy of 10-Hz rTMS applied to the left dorsolateral prefrontal cortex for the treatment of predominant negative symptoms in schizophrenia. Methods A multicenter randomized, sham-controlled, rater-blinded and patient-blinded trial was conducted from 2007–2011. Investigators randomly assigned 175 patients with schizophrenia with predominant negative symptoms and a high-degree of illness severity into two treatment groups. After a 2-week pretreatment phase, 76 patients were treated with 10-Hz rTMS applied 5 days per week for 3 weeks to the left dorsolateral prefrontal cortex (added to the ongoing treatment), and 81 patients were subjected to sham rTMS applied similarly. Results There was no statistically significant difference in improvement in negative symptoms between the two groups at day 21 ( p = .53, effect size=.09) or subsequently through day 105. Also, symptoms of depression and cognitive function showed no differences in change between groups. There was a small, but statistically significant, improvement in positive symptoms in the active rTMS group ( p = .047, effect size=.30), limited to day 21. Conclusions Application of active 10-Hz rTMS to the left dorsolateral prefrontal cortex was well tolerated but was not superior compared with sham rTMS in improving negative symptoms; this is in contrast to findings from three meta-analyses.

Background Increased variability of stimulus-induced prefrontal electromagnetic activity ("noise") has been associated with genetic risk for schizophrenia. On the basis of animal experiments and computational models, we have predicted that this prefrontal "noise" phenotype would be related to variation in prefrontal dopamine (DA) signaling, which itself might be abnormal in schizophrenia. In the present study, the effect of a functional single nucleotide polymorphism (val 108/158 met) within the catechol- O -methyltransferase (COMT) gene on prefrontal "noise" was examined, because the COMT enzyme is involved in cortical synaptic dopamine metabolism and weakly predictive of risk for schizophrenia. Methods A Caucasian sample comprising 112 unrelated normal subjects, 83 schizophrenic probands, and 87 of their unaffected siblings was investigated, all of whom had measures of prefrontal "noise" estimated from event-related electroencephalogram during an auditory oddball task. Results The val 108/158 met genotype was significantly associated with prefrontal "noise"; homozygous Val-carriers had greatest prefrontal "noise" values; odds ratio (OR) = 2.37 (95% confidence interval [CI] 1.37–4.10), p = 003. The genotype-phenotype association was stronger when only considering male subjects with an OR=3.37 (95% CI: 1.63–6.98), p = 002. Conclusions The results suggest that COMT genotype impacts the level of prefrontal physiologic "noise."

Chronic smoking and nicotine exposure are accompanied by impaired cognitive task performance, modulated cerebral activity in brain imaging studies, and neuritic damage in experimental animals. The profile of the described dysfunctions matches frontal lobe circuits which also play a role in reward processing and reinforcement behavior. However, it is largely unknown if cerebral dysfunctions are reversible or persist during long term abstinence. Cortical activation during auditory target processing (oddball task, P300 component) was recorded with 32-channel EEG in 247 healthy subjects consisting of 84 smokers, 53 former smokers (mean time of abstinence 11.9 years), and 110 never smokers. Both current smokers and former smokers exhibited significantly diminished P300 amplitudes (Cz, Pz) relative to never smokers. Neuroelectric source analysis (low resolution brain electromagnetic tomography) revealed a hypoactivation of the anterior cingulate, orbitofrontal, and prefrontal cortex in smokers compared to never smokers. A similar profile of hypoactivation was observed in former smokers. For the first time, evidence is provided that dysfunctional activation of frontal lobe networks in smokers is also present in long term abstainers.

Objective Integration of sensory information by cortical network binding appears to be crucially involved in target detection. Studies in schizophrenia using functional and diffusion tensor neuroimaging, event-related potentials and EEG coherence indicate an impairment of cortical network coupling in this disorder. Previous electrophysiological investigations in animals and humans suggested that gamma activity (oscillations at around 40 Hz) is essential for cortical network binding. Studies in medicated schizophrenia provide evidence for a reduced gamma activity in the context of auditory stimulus processing. This is the first investigation of oscillatory activations in the gamma-band in an auditory oddball paradigm in unmedicated schizophrenic patients. Methods EEG gamma-band responses (GBRs) of 15 drug-free schizophrenic patients and 15 age- and gender-matched healthy controls were compared. A wavelet transform based on Morlet wavelets was employed for the calculation of oscillatory GBRs. Results In response to standard stimuli, early evoked GBRs (20–100 ms), which are supposed to reflect auditory cortex activation, did not show significant group differences. However, schizophrenic patients showed reduced evoked GBRs in a late latency range (220–350 ms), particularly after target stimuli. This deficit occurred over right frontal scalp regions. Furthermore, significant correlations were observed between oscillatory GBRs and clinical parameters in schizophrenic patients. Conclusions The results are consistent with a relative preserved stimulus processing in the auditory cortex as reflected by the early GBR. The reduced late GBR is compatible with an abnormal interaction within a frontal lobe network, as was postulated by previous neuroimaging studies. Significance The present study provides evidence for disturbed processing within frontal cortical regions in unmedicated schizophrenic patients as indicated by reduced evoked EEG GBRs.

Mild cognitive impairment (MCI) is considered to be a transitional stage between normal aging and dementia. In Alzheimer’s disease (AD), white matter structural pathology is due to Wallerian degeneration and central angiopathy. However, in MCI patients, the presence and extent of white matter alterations as a possible correlate of impaired memory function and as predictor of subsequent progression to AD is not clarified yet. Diffusion tensor imaging (DTI) reveals the ultrastructural integrity of cerebral white matter tracts. Therefore, it could detect pathological processes that modify tissue integrity in patients with MCI. In our prospective study, conventional and diffusion tensor MR scans were obtained from 14 patients with MCI, 19 patients with AD, and 10 healthy controls. Mean diffusivity (MD) and fractional anisotropy (FA) were measured in temporal, frontal, parietal and occipital white matter regions as well as in the corpus callosum (genu and splenium) and the hippocampus. MCI patients showed higher MD values in the left centrum semiovale (p = 0.013; right: p = 0.026), in the left temporal (p = 0.006), the right temporal (p = 0.014) and the left hippocampal (p = 0.002) region as compared to the control group. FA values of MCI patients and controls did not differ significantly in any region. Compared to controls, AD patients had increased MD values in the left centrum semiovale (p = 0.012), the left parietal (p = 0.001), the right parietal (p = 0.028), the left temporal (p = 0.018), the right temporal (p = 0.011) and the left hippocampal region (p = 0.002). Decreased FA values were measured in the left temporal area (p = 0.017) and in the left hippocampus (p = 0.031) in AD patients compared to controls. FA and MD values did not differ significantly between AD and MCI patients. Elevated MD values indicating brain tissue alterations in MCI patients were found in regions that are typically involved in early changes due to AD, particularly the left hippocampus. The sensitivity of distinguishing MCI patients from controls was 71.4% (with a specificity set at 80%). Therefore, the DTI technique validates the MCI concept, and diffusion tensor MR measurement can be a helpful tool to quantify MCI pathology in vivo.

Evolution of the prefrontal cortex was an essential precursor to civilization. During the past decade, it became increasingly obvious that human prefrontal function is under substantial genetic control. In particular, heritability studies of frontal lobe-related neuropsychological function, electrophysiology and neuroimaging have greatly improved our insight. Moreover, the first genes that are relevant for prefrontal function such as catechol-O-methyltransferase (COMT) are currently discovered. In this review, we summarize the present knowledge on the genetics of human prefrontal function. For historical reasons, we discuss the genetics of prefrontal function within the broader concept of general cognitive ability (intelligence). Special emphasis is also given to methodological concerns that need to be addressed when conducting research on the genetics of prefrontal function in humans.

Objective: Electroencephalography (EEG) power and coherence changes may be trait markers for alcoholism providing clues to brain mechanisms of vulnerability. However, it is unclear whether alpha power and coherence differences reflect reversible toxic or withdrawal effects of alcohol. Method: The EEGs of 10 non-abstinent and 16 long-term abstinent alcoholics (7.7 ± 5.8 years) and 25 controls were analyzed. Levels of anxiety and depression were assessed by questionnaire. Results: No statistically significant EEG power differences were observed between groups, although the numerical difference between alcoholics and controls was similar to that previously reported. Bilateral, intrahemispheric, posterior coherences were significantly increased in the alpha and beta frequency bands both in long-term abstinent and non-abstinent alcohol-dependent subjects – particularly when depressiveness was included as a covariate. Conclusion: These results suggest that increased EEG-coherence (cortical synchronization) may serve as endophenotype for alcoholism in conjunction with increased depressiveness and point to a possible involvement of GABAergic and/or glutamatergic neurotransmission.

Current concepts of cognitive control suggest that the anterior cingulate cortex (ACC) is involved in performance monitoring. This idea is supported by the finding that increased ACC activity is found in situations in which errors are likely to occur, even if none are actually made. In addition, recent results suggest that increased ACC activity is negatively correlated with reaction time. We have now compared the error rates and the ACC activity of healthy subjects with short (n=19) vs. long reaction times (n=17) in an auditory choice reaction paradigm and analysed the current density differences in the ACC in the time range of the N1 component with low resolution electromagnetic tomography. Subjects with short reaction times showed significantly more ACC activation (Brodmann Area 24) and an increased error rate. This finding suggests that increased ACC activity is associated with a gain in reaction speed at the expense of correctness and is discussed in the context of current concepts about the role of the ACC in cognitive functions.

This study was performed in order to address the question whether the newly introduced technique of low-resolution electromagnetic tomography (LORETA) is able to detect hypofrontality in schizophrenic patients. We investigated resting EEGs of 19 unmedicated schizophrenics and 20 normal subjects. For comparison, we also investigated 19 subjects with schizotypal personality and 30 unmedicated depressive patients. A significant increase of delta activity was found in schizophrenic patients over the whole cortex, most strongly in the anterior cingulate gyrus and temporal lobe (fusiform gyrus). Both schizotypal subjects and depressive subjects showed significantly less delta, theta and beta activity in the anterior cingulum, a decrease of alpha1 activity in the right temporal lobe and a decrease of alpha2 activity in the left temporal lobe. The results suggest general cortical hypoactivation, most pronounced in the anterior cingulate and temporal lobe in schizophrenics, whereas there is evidence for a complex, frequency-dependent spatial pattern of hyperactivation in schizotypal subjects and depressive patients. The results are discussed within a neurophysiological and methodological framework.

We used l -(quinoxalin-6-ylcarbonyl)piperidine (CX516) (a modulator of the α-amino-3-hydroxy-5-methyl-4-isoxasole propionic acid (AMPA) receptor) as a sole agent in a double blind placebo-controlled design in a small series of patients with schizophrenia who were partially refractory to treatment with traditional neuroleptics. The study entailed weekly increments in doses of CX516, from 300 mg tid for week 1 up to 900 mg tid on week 4. Patients were followed with clinical ratings, neuropsychological testing, and were monitored for adverse events. Four patients received 2 to 4 weeks of CX516, two received placebo and two withdrew during the placebo phase. Adverse events associated with drug administration were transient and included leukopenia in one patient and elevation in liver enzymes in another. No clear improvement in psychosis or in cognition was observed over the course of the study. CX516 at the doses tested did not appear to yield dramatic effects as a sole agent, but inference from this study is limited.

Current concepts of the anterior cingulate cortex (ACC) increasingly emphasize its role as an interface between limbic and neocortical functions. It has been pointed out that ACC activation reflects the intentional amount of effort (volition) that a subject uses in a task. In previous electrophysiological source localization investigations during a choice reaction task, we described a strong early activation in the ACC region approximately 120–150 ms after stimulus presentation. The degree of midline ACC activation correlated negatively with reaction time. This observation together with the finding that ACC activation precedes information processing in cortical association areas provided preliminary support to the notion that the extent of ACC activation is related to a subject's task engagement. However, due to the inverse problem and the relatively low spatial resolution of the electrophysiological measurements, we were not able to make inferences about the validity and the exact localization of the observed midline activation maximum. We addressed this question and performed an event-related fMRI study in six healthy volunteers during a visual choice reaction task. Two checkerboard stimuli were presented either in the left or right visual hemifield in randomized order and with an interstimulus interval requiring an appropriate motor response (left–right button press). A bilateral BOLD maximum was observed in the region of the supplementary motor area confluent with the neighboring motor area of the dorsal ACC. The degree of ACC activation correlated significantly with reaction time. These results are in line with our previous electrophysiological findings and provide further evidence that early ACC activation during a choice reaction task reflects the intentional effort of a subject to carry out a task.

Functional dissociation between brain processes is widely hypothesized to account for aberrations of thought and emotions in schizophrenic patients. The typically small groups of analyzed schizophrenic patients yielded different neurophysiological findings, probably because small patient groups are likely to comprise different schizophrenia subtypes. We analyzed multichannel eyes- closed resting EEG from three small groups of acutely ill, first episode productive schizophrenic patients before start of medication (from three centers: Bern N = 9; Osaka N = 9; Berlin N = 12) and their controls. Low resolution brain electromagnetic tomography (LORETA) was used to compute intracortical source model-based lagged functional connectivity not biased by volume conduction effects between 19 cortical regions of interest (ROIs). The connectivities were compared between controls and patients of each group. Conjunction analysis determined six aberrant cortical functional connectivities that were the same in the three patient groups. Four of these six concerned the facilitating EEG alpha-1 frequency activity; they were decreased in the patients. Another two of these six connectivities concerned the inhibiting EEG delta frequency activity; they were increased in the patients. The principal orientation of the six aberrant cortical functional connectivities was sagittal; five of them involved both hemispheres. In sum, activity in the posterior brain areas of preprocessing functions and the anterior brain areas of evaluation and behavior control functions were compromised by either decreased coupled activation or increased coupled inhibition, common across schizophrenia subtypes in the three patient groups. These results of the analyzed three independent groups of schizophrenics support the concept of functional dissociation.

Background: Event-related potentials (ERPs) during an auditory oddball task were investigated in patients with schizophrenia and in their healthy siblings to explore the question of whether abnormalities of two-dimensional topographic scalp-distribution of P300 amplitude and latency relate to genetic risk for schizophrenia. We also examined the P50, N100, and P200-waves, elicited during the same task. Methods: We investigated 42 schizophrenic patients, 62 of their healthy siblings, and 34 unrelated normal control subjects with a standard auditory oddball paradigm and 16 electroencephalogram electrodes. Amplitudes and latencies of the ERPs P50, N100, P200, and P300 were topographically analyzed. Results: In the patients, P300 amplitude was significantly decreased in the range of 54%–58% over the left parietotemporal area. Siblings did not show decreased P300 amplitudes when compared with normal subjects. P300 latencies were unchanged in both groups. No significant group differences were observed for the other event-related potentials. Conclusions: In line with previous studies, the P300 amplitude in schizophrenic patients was decreased over the left temporoparietal area; however, we found no evidence for a genetic trait effect in the event-related potential abnormality. Possible reasons for these largely negative findings are discussed.

It was the aim of the present study 1) to investigate how many cortical activity maxima of scalp-recorded P300 are detected by Low Resolution Electromagentic Tomography (LORETA) when analyses are performed with high time-resolution, 2) to see if the resulting LORETA-solution is in accordance with intracortical recordings as reported by others and 3) to compare the given pattern of cortical activation maxima in the P300-timeframe between schizophrenic patients and normal controls. Current density analysis was performed in 3-D Talairach space with high time resolution i.e. in 6 ms steps. This was done during an auditory choice reaction paradigm separately for normal subjects and schizophrenic patients with subsequent group comparisons. In normal subjects, a sequence of at least seven cortical activation maxima was found between 240-420ms poststimulus: the prefrontal cortex, anterior or medial cingulum, posterior cingulum, parietal cortex, temporal lobe, prefrontal cortex, medial or anterior cingulum. Within the given limits of spatial resolution, this sequential maxima distribution largely met the expectations from reports on intracranial recordings and functional neuroimaging studies. However, localization accuracy was higher near the central midline than at lateral aspects of the brain. Schizophrenic patients less activated their cortex in a widespread area mainly in the left hemisphere including the prefrontal cortex, posterior cingulum and the temporal lobe. From these analyses and comparsions with intracranial recordings as reported by others, it is concluded that LORETA correctly localizes P300-related cortical activity maxima on the basis of 19 electrodes except for lateral cortical aspects which is most likely an edge-phenomenon. The data further suggest that the P300-deficit in schizophrenics involves an extended cortical network of the left hemisphere at several steps in time during the information processing stream.

We analyzed a novel functional 30-bp repeat polymorphism in the promoter region of the X-chromosomal monoamine oxidase A gene (MAOA) to test whether length variation of the repeat polymorphism contributes to variation in the individual vulnerability to antisocial behavior and liability to alcohol dependence. The repeat number (3-5) of the MAOA polymorphism was assessed in 488 male subjects of German descent, a sample comprising 185 psychiatrically screened control subjects and 303 alcohol-dependent subjects including 59 alcoholics with antisocial personality disorder. The frequency of the low-activity 3-repeat allele was significantly increased in 59 antisocial alcoholics compared to 185 control subjects (51 vs. 35%; P = 0.031) and to 244 alcoholics without antisocial personality disorder (51 vs. 32%; P = 0.008), respectively. We found no significant difference in the frequency of the 3-repeat allele between 244 alcoholics without an antisocial personality disorder and the control subjects. Our findings suggest that the low-activity 3-repeat allele of the MAOA promoter polymorphism confers increased susceptibility to antisocial behavior rather than alcohol dependence per se in alcohol-dependent males.

The capability of predicting relapse in chronic alcoholism using quantitative EEG was investigated. For this purpose, 78 in-patients with alcoholism underwent EEG recordings (eyes closed) 7 days after the beginning of detoxification. Additionally, other clinical evaluations were carried out. After discharge from hospital, patients were regularly re-evaluated for the duration of 3 months in order to determine whether they relapsed or abstained from alcohol during this time. For classification of the two diagnostic subgroups (relapsers vs. abstainers), multivariate discriminant analysis as well as artificial neural network technology has been applied. Correct classification of patients' EEGs was achieved in 83-85% and thus outperformed classification with clinical variables considerably. Furthermore, artificial neural networks (ANN) improved classification results when compared with discriminant analysis. It was found that, in comparison to abstainers, relapsers had EEGs that were more desynchronized over frontal areas, which was interpreted as a functional disturbance of the prefrontal cortex.

Decision-making is an everyday routine that entails several subprocesses. Decisions under uncertainty occur when either prior information is incomplete or the outcomes of the decision are unclear. The aim of the present study was to disentangle the neural correlates of information gathering as well as reaching a decision and to explore effects of uncertainty acceptance or avoidance in a large sample of healthy subjects. Sixty-four healthy volunteers performed a decision-making under uncertainty task in a multi-center approach while BOLD signal was measured with fMRI. Subjects either had to indicate via button press from which of two bottles red or blue balls were drawn (decision-making under uncertainty condition), or they had to indicate whether 8 red balls had been presented (baseline condition). During the information gathering phase (contrasted against the counting phase) a widespread network was found encompassing (pre-)frontal, inferior temporal and inferior parietal cortices. Reaching a decision was correlated with activations in the medial frontal cortex as well as the posterior cingulate and the precuneus. Effects of uncertainty acceptance were found within a network comprising of the superior frontal cortex as well as the insula and precuneus while uncertainty avoidance was correlated with activations in the right middle frontal cortex. The results depict two distinct networks for information gathering and the indication of having made a decision. While information-gathering networks are modulated by uncertainty avoidance and – acceptance, underlying networks of the decision itself are independent of these factors.

Various quantitative descriptors for EEG data will be compared taking sleep as an example. In this contribution, Hjorth’s mobility and complexity measures will be used to classify sleep stages. The results will be compared with those of a dimensionality analysis. Several authors have shown that the correlation exponent can describe the complexity of sleep EEG data and is able – with the exception of REM sleep – to distinguish significantly between sleep stages. The discriminative power of a bivariate global frequency analysis appears to be superior to that of the correlation exponent. Furthermore a very high statistical correlation between the estimator of fractal dimension and Hjorth’s mobility was obtained.

Human brain lesion studies first investigated the biological roots of cognitive functions including language in the late 1800s. Neuroimaging studies have reported correlation findings with general intelligence predominantly in fronto-parietal cortical areas. However, there is still little evidence about the relationship between verbal intelligence and structural properties of the brain. We predicted that verbal performance is related to language regions of Broca's and Wernicke's areas. Verbal intelligence quotient (vIQ) was assessed in 30 healthy young subjects. T1-weighted MRI and diffusion tensor imaging data sets were acquired. Voxel-wise regression analyses were used to correlate fractional anisotropy (FA) and mean diffusivity values with vIQ. Moreover, regression analyses of regional brain volume with vIQ were performed adopting voxel-based morphometry (VBM) and ROI methodology. Our analyses revealed a significant negative correlation between vIQ and FA and a significant positive correlation between vIQ and mean diffusivity in the left-hemispheric Broca's area. VBM regression analyses did not show significant results, whereas a subsequent ROI analysis of Broca's area FA peak cluster demonstrated a positive correlation of gray matter volume and vIQ. These findings suggest that cortical thickness in Broca's area contributes to verbal intelligence. Diffusion parameters predicted gray matter ratio in Broca's area more sensitive than VBM methodology.

Alterations of hippocampal anatomy have been reported consistently in schizophrenia. Within the present study, we used FreeSurfer to determine hippocampal subfield volumes in 21 schizophrenic patients. A negative correlation between PANSS-positive symptom score and bilateral hippocampal subfield CA2/3 as well as CA1 volume was found on high-resolution magnetic resonance images. Our observation opens the gate for advanced investigation of the commonly reported hippocampal abnormalities in schizophrenia in terms of specific subfields.