Cortical thickness across the cingulate gyrus in schizophrenia and its association to illness duration and memory performance.

Schizophrenia has been associated with structural brain abnormalities and cognitive deficits that partly change during the course of illness. In the present study, cortical thickness in five subregions of the cingulate gyrus was assessed in 44 patients with schizophrenia-spectrum disorder and 47 control persons and related to illness duration and memory capacities. In the patients group, cortical thickness was increased in the posterior part of the cingulate gyrus and related to illness duration whereas cortical thickness was decreased in anterior parts unrelated to illness duration. In contrast, cortical thickness was related to episodic and working memory performance only in the anterior but not posterior parts of the cingulate gyrus. Our finding of a posterior cingulate increase may point to either increased parietal communication that is accompanied by augmented neural plasticity or to effects of altered neurodegenerative processes in schizophrenia.

Size matters: Grey matter brain reserve predicts executive functioning in the elderly.

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 ±â€¯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 = 0.001-0.012). 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.

Personalized risk prediction of postoperative cognitive impairment - rationale for the EU-funded BioCog project.

Postoperative cognitive impairment is among the most common medical complications associated with surgical interventions - particularly in elderly patients. In our aging society, it is an urgent medical need to determine preoperative individual risk prediction to allow more accurate cost-benefit decisions prior to elective surgeries. So far, risk prediction is mainly based on clinical parameters. However, these parameters only give a rough estimate of the individual risk. At present, there are no molecular or neuroimaging biomarkers available to improve risk prediction and little is known about the etiology and pathophysiology of this clinical condition. In this short review, we summarize the current state of knowledge and briefly present the recently started BioCog project (Biomarker Development for Postoperative Cognitive Impairment in the Elderly), which is funded by the European Union. It is the goal of this research and development (R&D) project, which involves academic and industry partners throughout Europe, to deliver a multivariate algorithm based on clinical assessments as well as molecular and neuroimaging biomarkers to overcome the currently unsatisfying situation.

Hypertension and Risk of Post-Operative Cognitive Dysfunction (POCD): A Systematic Review and Meta-Analysis.

BACKGROUND: Post-operative cognitive dysfunction (POCD) occurs frequently after major surgery. Hypertension is well-established as a risk factor for age-related cognitive impairment, but it is unclear whether or not it also increases the risk of POCD. OBJECTIVE: To evaluate the role of hypertension in POCD risk in a systematic review and meta-analysis. METHOD: PubMed, Ovid SP and the Cochrane Database of Systematic Reviews were searched for longitudinal studies of adults undergoing surgery with reporting of hypertension, blood pressure and/or anti-hypertensive treatment associations with POCD as relative risks or odds ratios. Fixed-effects meta-analyses were performed using Review Manager (version 5.3). RESULTS: Twenty-four studies on 4317 patients (mean age 63 years) were included. None of the studies had set out to assess hypertension as a risk factor for POCD. Hypertension was used as a categorical predictor throughout and only 2 studies adjusted for potential confounders. Across all 24 studies, hypertension was not significantly associated with POCD risk (RR 1.01; 95% CI 0.93, 1.09; p=0.82), though among 8 studies with >75% males, we found hypertension associations with a 27% increased risk of POCD (RR 1.27, 95% CI 1.07, 1.49; p=0.005). CONCLUSION: Our findings do not support the hypothesis that hypertension is a risk factor for POCD. However, since none of the studies included in our analysis were hypothesis-driven and most did not adjust for potential confounders, further systematic investigations are needed to evaluate the role of hypertension in the epidemiology of POCD.

Diabetes is associated with risk of postoperative cognitive dysfunction: A meta-analysis.

BACKGROUND: Postoperative cognitive dysfunction (POCD) occurs frequently after surgery, particularly among older people. Diabetes, chronic hyperglycemia, and a history of hypoglycemia are related to cognitive impairment, but little is known about their roles in POCD. Here, we estimated their associations with risk of POCD on the basis of published epidemiological research. METHODS: The PubMed and Cochrane databases were searched for longitudinal studies of adults undergoing surgery with reporting of associations of diabetes status, glycemic levels, and/or a history of hypoglycemia with risk of POCD as relative risks or odds ratios. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) and Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed. RESULTS: The search identified 246 publications of which 14 met inclusion criteria, reporting on a total of 2642 patients (mean age 64 y). Follow-up periods spanned 1 day to 5 years. Overall, patients with diabetes had a 1.26-fold higher risk of POCD compared with diabetes-free patients (95% CI, 1.12-1.42). A single study assessed glycemic control in patients with diabetes and identified a higher hemoglobin A1c (HbA1c) level as associated with higher POCD risk (relative risk per percent higher HbA1c, 2.0; 95% CI, 1.4-2.6). We did not find studies on glycemic levels in the nondiabetic range or on hypoglycemia as potential predictors of POCD. CONCLUSION: Patients with diabetes appear to have a higher risk of POCD compared with diabetes-free persons. Among patients with diabetes, POCD risk may further increase with poorer glycemic control as indexed by higher HbA1c. The roles of HbA1c levels among nondiabetic persons in POCD risk warrant further research.

Structural brain changes are associated with response of negative symptoms to prefrontal repetitive transcranial magnetic stimulation in patients with schizophrenia.

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.

Association of Common Polymorphisms in the Nicotinic Acetylcholine Receptor Alpha4 Subunit Gene with an Electrophysiological Endophenotype in a Large Population-Based Sample.

Variation in genes coding for nicotinic acetylcholine receptor (nAChR) subunits affect cognitive processes and may contribute to the genetic architecture of neuropsychiatric disorders. Single nucleotide polymorphisms (SNPs) in the CHRNA4 gene that codes for the alpha4 subunit of alpha4/beta2-containing receptors have previously been implicated in aspects of (mostly visual) attention and smoking-related behavioral measures. Here we investigated the effects of six synonymous but functional CHRNA4 exon 5 SNPs on the N100 event-related potential (ERP), an electrophysiological endophenotype elicited by a standard auditory oddball. A total of N = 1,705 subjects randomly selected from the general population were studied with electroencephalography (EEG) as part of the German Multicenter Study on nicotine addiction. Two of the six variants, rs1044396 and neighboring rs1044397, were significantly associated with N100 amplitude. This effect was pronounced in females where we also observed an effect on reaction time. Sequencing of the complete exon 5 region in the population sample excluded the existence of additional/functional variants that may be responsible for the observed effects. This is the first large-scale population-based study investigation the effects of CHRNA4 SNPs on brain activity measures related to stimulus processing and attention. Our results provide further evidence that common synonymous CHRNA4 exon 5 SNPs affect cognitive processes and suggest that they also play a role in the auditory system. As N100 amplitude reduction is considered a schizophrenia-related endophenotype the SNPs studied here may also be associated with schizophrenia outcome measures.

Investigation of decision-making under uncertainty in healthy subjects: a multi-centric fMRI study.

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.

Attenuated prefrontal activation during decision-making under uncertainty in schizophrenia: a multi-center fMRI study.

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.

Hippocampal subfields predict positive symptoms in schizophrenia: first evidence from brain morphometry.

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.

DTNBP1 (dysbindin) gene variants: in vivo evidence for effects on hippocampal glutamate status.

INTRODUCTION: In linkage and association studies the DTNBP1 gene has been identified as a major susceptibility gene for schizophrenia. Reduced expression of DTNBP1 was found in the hippocampus and prefrontal cortex in post mortem brains of schizophrenic patients. In vitro and animal models provide evidence that the DTNBP1 gene product dysbindin modulates the activity of the neurotransmitter glutamate in hippocampal neurons and is crucial for cell functioning and synaptogenesis. This study is the first to investigate the effects of genetic variants of DTNBP1 on the status of the glutamate system as well as neuronal integrity (N-acetylaspartate, NAA) in the hippocampus and a cortical region, the anterior cingulate cortex (ACC), in humans. METHODS: In 79 healthy subjects, the association of single nucleotide polymorphisms (SNPs) rs760665 and rs909706 with absolute concentrations of glutamate and NAA in the left hippocampus and the ACC were investigated, using proton magnetic resonance spectroscopy (MRS) at 3 Tesla and a well established quantification procedure. RESULTS: Hippocampal glutamate concentration was significantly affected by genotype of rs760665 (F=4.406, df=2,p=0.016) and rs909706 (F=3.171,df=2,p=0.048). For the concentration of NAA, a weak association with rs760665 was observed in the contrast analysis. None of the metabolites measured in the ACC showed a significant connection with either genotype. CONCLUSION: The results support a role of DTNBP1 gene variants in the glutamate neurotransmission system in the human brain at least in the hippocampus. This is compatible to growing evidence of a crucial role of glutamate in the pathobiology of schizophrenia. In addition, the weak association between DTNBP1 genotype and NAA is in line with a regulatory influence of dysbindin on synaptogenesis and neuronal survival.

The P300 event-related potential and smoking--a population-based case-control study.

A better understanding of the factors underlying habitual tobacco smoking may further new strategies to go about this major health problem. The P300 event-related potential (ERP) has emerged as a valuable (endo)phenotype in neuropsychiatric research. Previous studies suggested the P300 ERP to be reduced in smokers. The main purpose of the present study was to provide an in-depth description of smoking-related behavioral, biological and electrophysiological phenotypes with an emphasis on the P300 ERP and its mutual relationship with other smoking-related parameters. In this case-control study N=1318 participants (smokers and never-smoking controls) were investigated at 6 German academic institutions. Study participants were randomly selected from the general population. Subjects with mental disorders including alcoholism and drug abuse were excluded. The main outcome measure was the P300 global field power (GFP). We found a lower P300 GFP in current smokers compared to never-smoking controls. Furthermore a correlation between measures of smoking severity and P300 GFP reduction was found. Non-addicted smokers exhibited normal P300 ERP measures. This study provides further evidence that the P300 ERP is reduced in current smokers even in the absence of potentially confounding psychiatric comorbidity. Thus, P300 amplitude reduction clearly is part of the electrophysiological phenotype of smokers. Our results provide the phenotypical groundwork for future multidimensional analyses of genotype-phenotype relationships in the field of smoking and nicotine dependence.

Spontaneous brain activity and EEG microstates. A novel EEG/fMRI analysis approach to explore resting-state networks.

The brain is active even in the absence of explicit input or output as demonstrated from electrophysiological as well as imaging studies. Using a combined approach we measured spontaneous fluctuations in the blood oxygen level dependent (BOLD) signal along with electroencephalography (EEG) in eleven healthy subjects during relaxed wakefulness (eyes closed). In contrast to other studies which used the EEG frequency information to guide the functional MRI (fMRI) analysis, we opted for transient EEG events, which identify and quantify brain electric microstates as time epochs with quasi-stable field topography. We then used this microstate information as regressors for the BOLD fluctuations. Single trial EEGs were segmented with a specific module of the LORETA (low resolution electromagnetic tomography) software package in which microstates are represented as normalized vectors constituted by scalp electric potentials, i.e., the related 3-dimensional distribution of cortical current density in the brain. Using the occurrence and the duration of each microstate, we modeled the hemodynamic response function (HRF) which revealed BOLD activation in all subjects. The BOLD activation patterns resembled well known resting-state networks (RSNs) such as the default mode network. Furthermore we "cross validated" the data performing a BOLD independent component analysis (ICA) and computing the correlation between each ICs and the EEG microstates across all subjects. This study shows for the first time that the information contained within EEG microstates on a millisecond timescale is able to elicit BOLD activation patterns consistent with well known RSNs, opening new avenues for multimodal imaging data processing.

The tolerability of rTMS treatment in schizophrenia with respect to cognitive function.

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.

Brain activation patterns underlying fast habituation to painful laser stimuli.

A painful experience is modified by processes like habituation/antinociception or sensitization. Altered habituation may be one characteristic of chronic pain syndromes. In the present study we sought to investigate the functional magnetic resonance imaging (fMRI) blood oxygen level dependent (BOLD) correlate of rapid habituation to pain using simultaneous single trial electrodermal activity (EDA)/fMRI measurements. A total of N=32 healthy subjects have been investigated. Subjects received painful laser stimulation of the left hand. The fMRI BOLD response was measured simultaneously with continuous EDA recordings. Single trial EDA responses to laser stimulation habituated over time with substantial subject-to-subject differences in the degree and speed of habituation. fMRI BOLD habituation was assessed by contrasting the first half of the experiment against the second half and was found in primary and secondary somatosensory cortices, the insula and the anterior cingulate cortex (ACC). We hypothesized that single trial EDA habituation would reflect BOLD habituation which was investigated separately in subjects with 'faster' (N=15) and 'slower' (N=14) EDA habituation. Significant habituation of the BOLD signal was only found in subjects with 'faster' EDA habituation that was accompanied by a signal increase in the rostral ACC and the periaqueductal grey. Furthermore, subjects with faster EDA habituation provided lower pain ratings. Therefore the EDA habituation profile to painful stimulation may constitute a pain-related (endo)phenotype and may be an informative additional endpoint measure in fMR-imaging of pain, especially when people suffering from chronic pain states in which pain processing is often altered are studied.

Association of a variant in the muscarinic acetylcholine receptor 2 gene (CHRM2) with nicotine addiction.

Genetic factors contribute to the overall risk of developing nicotine addiction, which is the major cause of preventable deaths in western countries. However, knowledge regarding specific polymorphisms influencing smoking phenotypes remains scarce. In the present study we provide evidence that a common single nucleotide polymorphism (SNP) in the 5' untranslated region of CHRM2, the gene coding for the muscarinic acetylcholine receptor 2 is associated with nicotine addiction. CHRM2 was defined as a candidate gene for nicotine addiction based on previous evidence that linked variations in CHRM2 to alcohol and drug dependence. A total of more than 5,500 subjects representative of the German population were genotyped and assessed regarding their smoking habits. The impact of three SNPs in CHRM2 on smoking behavior/nicotine addiction was investigated using logistic regression models or a quasi-Poisson regression model, respectively. We found the T allele of SNP rs324650 to be associated with an increased risk of smoking/nicotine dependence according to three different models, the recessive models of regular or heavy smokers vs. never-smokers (odds ratio 1.17 in both analyses) and according to the Fagerström index of nicotine addiction. In the analysis stratified by gender this association was only found in females. Our data provide further evidence that variations in CHRM2 may be associated with the genetic risk of addiction in general or with certain personality traits that predispose to the development of addiction. Alternatively, variations in CHRM2 could modulate presynaptic auto-regulation in cholinergic systems and may thereby affect an individual's response to nicotine more specifically.

Neuroprotective and neurotoxic effects of nicotine.

The interest in the action of nicotine in the central nervous system (CNS) has significantly increased during the past 15 years. This is due in part to the growing importance of nicotine addiction and its consequences in terms of life quality and costs for public health systems in industrialized countries and, on the other hand, to the significantly higher prevalence of tobacco consumption in patients with psychiatric disorders. The actual data indicate opposite effects of nicotine in the CNS. Nicotine seems to have, at the same time, positive, neuroprotective as well as negative, neurotoxic effects. This suggests that nicotine's action is complex, probably involving different neuronal circuits influencing each other through complicated interactions. In the present review we summarize the most important results of experiments about nicotinic neuroprotection and neurotoxicity in humans and animals. Initially, we illustrate well known modifications of cholinergic transmission during physiological (normal aging) and pathological neurodegeneration. In the second part of the paper we describe neuroprotective and neurotoxic effects of nicotine also mentioning the underlying molecular mechanisms.

Repetitive transcranial magnetic stimulation for the treatment of negative symptoms in residual schizophrenia: rationale and design of a sham-controlled, randomized multicenter study.

Current meta-analysis revealed small, but significant effects of repetitive transcranial magnetic stimulation (rTMS) on negative symptoms in patients with schizophrenia. There is a need for further controlled, multicenter trials to assess the clinical efficacy of rTMS on negative symptoms in schizophrenia in a larger sample of patients. The objective of this multicenter, randomized, sham-controlled, rater- and patient-blind clinical trial is to investigate the efficacy of 3-week 10-Hz high frequency rTMS add on to antipsychotic therapy, 15 sessions per 3 weeks, 1,000 stimuli per session, stimulation intensity 110% of the individual motor threshold) of the left dorsolateral prefrontal cortex for treating negative symptoms in schizophrenia, and to evaluate the effect during a 12 weeks of follow-up. The primary efficacy endpoint is a reduction of negative symptoms as assessed by the negative sum score of the positive and negative symptom score (PANSS). A sample size of 63 in each group will have 80% power to detect an effect size of 0.50. Data analysis will be based on the intention to treat population. The study will be conducted at three university hospitals in Germany. This study will provide information about the efficacy of rTMS in the treatment of negative symptoms. In addition to psychopathology, other outcome measures such as neurocognition, social functioning, quality of life and neurobiological parameters will be assessed to investigate basic mechanisms of rTMS in schizophrenia. Main limitations of the trial are the potential influence of antipsychotic dosage changes and the difficulty to ensure adequate blinding.

[Biological correlates of prefrontal activating and temporoparietal inhibiting treatment with repetitive transcranial magnetic stimulation (rTMS)]. / Biologische Korrelate präfrontal aktivierender und temporoparietal inhibierender Behandlung mit repetitiver transkranieller Magnetstimulation (rTMS).

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.

Single-trial P3 amplitude and latency informed event-related fMRI models yield different BOLD response patterns to a target detection task.

Using single-trial parameters as a regressor in the General Linear Model (GLM) is becoming an increasingly popular method for informing fMRI analysis. However, the parameter used to characterise or to differentiate brain regions involved in the response to a particular task varies across studies (e.g. ERP amplitude, ERP latency, reaction time). Furthermore, the way in which the single-trial information is used in the fMRI analysis is also important. For example, the single-trial parameters can be used as regressors in the GLM or to modify the duration of the events modelled in the GLM. The aim of this study was to investigate the BOLD response to a target detection task when including P3 amplitude, P3 latency and reaction time parameters in the GLM. Simultaneous EEG-fMRI was recorded from fifteen subjects in response to a visual choice reaction time task. Including P3 amplitude as a regressor in the GLM yielded activation in left central opercular cortex, left postcentral gyrus, left insula, left middle frontal gyrus, left insula and left parietal operculum. Using P3 latency and reaction time as an additional regressor yielded no additional activation in comparison with the conventional fMRI analysis. However, when P3 latency or reaction time was used to determine the duration of events at a single-trial level, additional activation was observed in the left postcentral gyrus, left precentral gyrus, anterior cingulate cortex and supramarginal gyrus. Our findings suggest that ERP amplitudes and latencies can yield different activation patterns when used to modify relevant aspects of the GLM.