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Abstract: Time-variant Granger Causality Index (tvGCI) was applied to simulated and measured BOLD signals to investigate the reliability of time-variant analysis approaches for the identification of directed interrelations between brain areas on the basis of fMRI data. Single-shot fMRI data of a single image slice with short repetition times (200 ms, 16000 frames/subject, 64×64 voxels) were acquired from 5 healthy subjects during an externally-driven, self-paced finger-tapping paradigm (57–59 single taps for each subject). BOLD signals were derived from the pre-supplementary motor area (preSMA), the supplementary motor area (SMA), and the primary motor cortex (M1). The simulations were carried out by means of a Dynamic Causal Modelling (DCM) approach. The tvGCI as well as time-variant Partial Directed Coherence (tvPDC) were used to identify the modelled connectivity network (connectivity structure – CS – of the DCM). Different CSs were applied by using dynamic systems (Generalized Dynamic Neural Network — GDNN) and trivariate autoregressive (AR) processes. The influence of the low-pass characteristics of the simulated hemodynamic response (Balloon model) and of the measuring noise was tested. Additionally, our modelling strategy considered “spontaneous” BOLD fluctuations before, during, and after the appearance of the event-related BOLD component. Couplings which were extracted from the simulated signals were statistically evaluated (tvGCI for shuffled data, confidence tubes for tvGCI courses). We demonstrate that connections of our CS models can be correctly identified during the event-related BOLD component and with signal-to-noise-ratios corresponding to those of the measured data. The results based on simulations can be used to examine the reliability of connectivity identification based on BOLD signals by means of time-variant as well as time-invariant connectivity measures and enable a better interpretation of the analysis results using fMRI data. A readiness-BOLD response was only detected in one subject. However, in two subjects a strong time-variant connection (tvGCI) from preSMA to SMA was observed 3 s before the tapping was executed. This connection was accompanied by a weaker rise of the tvGCI from preSMA to M1. These preceding interrelations were confirmed in the other subjects by the dynamics of tvGCI courses. Based on the results of tvGCI analysis, the time-evolution of an individual connectivity network is shown for each subject. [Copyright &y& Elsevier]

Abstract: Functional imaging studies are indicating disrupted error monitoring and executive control in a fronto-cingulate network in major depression. However, univariate statistical analyses allow only for a limited assessment of directed neuronal interactions. Therefore, the present study used dynamic causal modeling (DCM) of a fronto-cingulate network to re-analyze the data from a preceding fMRI study in 16 drug-free patients with major depression and 16 healthy controls using the Stroop Color-Word Test (). In both groups, a significant reciprocal interregional connectivity was found in a cognitive control network including prefrontal cortex (PFC) and dorsal anterior cingulate cortex (ACC). With regard to intrinsic connections we detected a significant difference for dorsal to rostral ACC connectivity between depressive patients and controls in terms of higher connectivity in patients. Additionally, a task by group interaction was observed for the bilinear interaction signaling enhanced task-related input from the dorsal to rostral ACC in subjects with depression. This could be related to the inability of patients to down-regulate rostral ACC activation as observed in the previous univariate analysis. The correlation between interference scores and intrinsic connections from dorsal ACC to dorsolateral PFC (DLPFC) was significant for both groups together, but no significant group differences in correlations could be detected. Thus, the observed relationship between control functions of the dorsal ACC exerted over DLPFC and interference scores appears to be valid in both patients with depression and controls. The findings are consistent with current models of a differential involvement of the fronto-cingulate system in the pathophysiology of major depression. [Copyright &y& Elsevier]

Abstract: Working memory (WM) deficits are core symptoms of schizophrenia. Differing behavioral performance is known to represent a potent moderating variable when investigating the neural correlates of working memory in patients with schizophrenia compared with healthy controls. The present functional magnetic resonance imaging study examined performance-matched cerebral activity during correct WM retrieval by balancing the mean number of correct responses as well as the mean response times between patients and controls and analyzing remaining correct trials. Forty-one schizophrenia patients and 41 healthy controls performed an event-related Sternberg task allowing for analysis of correctly remembered trials. Correct retrieval was associated with activation in a bilateral fronto-parieto-occipital network comprising mainly the dorsolateral prefrontal cortex, ventrolateral prefrontal cortex and superior parietal cortex in controls and, to a weaker degree, in patients. Direct group comparison revealed significantly decreased activations in patients in the posterior (Brodmann area (BA) 31) and anterior (BA 32) cingulate cortex (ACC) and the medial caudate bilaterally when matching for performance. When matching for performance and response speed there was additional hypoactivation in the insula. Mean response times were negatively correlated with cingulate and caudate activation only in controls. Present findings suggest that during efficient WM retrieval processing patients exhibit only slightly impaired activation in a task-specific network containing mainly prefrontal and superior parietal areas. However, hypoactivation of areas predominantly responsible for cognitive control and response execution seems to remain even under performance-matched conditions. Given the relevant role of the caudate and the ACC in dopaminergically mediated executive processing, the results bear crucial implications for the psychopathology of schizophrenia. [Copyright &y& Elsevier]

Abstract: Working memory (WM) deficits are a core feature of schizophrenia. However, it has not been examined whether these deficits are related to altered temporal dynamics of information acquisition and changes in executive cognitive control. Therefore, the present study intended to quantify and model the dynamic process of information acquisition during continuous overlearning of WM information. It also aimed at investigating the relation between overlearning-associated change in behavioral performance and brain activity. Thirteen schizophrenic patients and 13 healthy volunteers were studied with functional magnetic resonance imaging (fMRI) while performing a recently developed overlearning paradigm [Koch K, Wagner G, von Consbruch K, Nenadic I, Schultz C, Ehle C, Reichenbach J, Sauer H, Schlösser R (2006) Temporal changes in neural activation during practice of information retrieval from short-term memory: An fMRI study. Brain Res 1107:140–150]. Consistent with the earlier study, short-term learning of stimulus material was associated with significant performance improvements and exponential signal decreases in a fronto-parieto-cerebellar network both in schizophrenic patients and in healthy volunteers. Against expectation patients exhibited stronger signal decreases relative to controls in anterior cingulate (Brodmann area (BA) 32), middle and superior temporal (BA 37, BA 22), superior frontal (BA 8/9, BA 6) and posterior parietal regions (BA 40). Furthermore, the individually modeled exponential decay rate of the blood oxygenation level-dependent signal in the right dorsolateral prefrontal cortex was significantly correlated with exponential decrease in mean behavioral response times in healthy controls while a statistical trend emerged in patients. A relative hyperactivation in the patient group was observable only at the start of the learning process and diminished with continued overlearning. This effect might indicate a gradual reduction of recruited neuronal resources and a practice-associated activation normalization in patients with schizophrenia. Our data suggest that in subacute patients learning and associated decreases in cerebral activation brought about by short-term practice are left unimpaired. [Copyright &y& Elsevier]