Kathrin Koch

Gender differences in the cognitive control of emotion: An fMRI study.

The interaction of emotion and cognition has become a topic of major interest. However, the influence of gender on the interplay between the two processes, along with its neural correlates have not been fully analysed so far. In this functional magnetic resonance imaging (fMRI) study we induced negative emotion using negative olfactory stimulation while male (n=21) and female (n=19) participants performed an n-back verbal working memory task. Based on findings indicating increased emotional reactivity in women, we expected the female participants to exhibit stronger activation in characteristically emotion-associated areas during the interaction of emotional and cognitive processing in comparison to the male participants. Both groups were found to be significantly impaired in their working memory performance by negative emotion induction. However, fMRI analysis revealed distinct differences in neuronal activation between groups. In men, cognitive performance under negative emotion induction was associated with extended activation patterns in mainly prefrontal and superior parietal regions. In women, the interaction between emotion and working memory yielded a significantly stronger response in the amygdala and the orbitofrontal cortex (OFC) compared to their male counterparts. Our data suggest that in women the interaction of verbal working memory and negative emotion is associated with relative hyperactivation in more emotion-associated areas whereas in men regions commonly regarded as important for cognition and cognitive control are activated. These results provide new insights in gender-specific cerebral mechanisms.

Reduced cortical thickness in first episode schizophrenia

OBJECTIVE Previous morphometric studies are suggesting altered cortical thickness mainly in prefronto-temporal regions in first episode schizophrenia. In an extension of these earlier studies, we used an entire cortex vertex-wise approach and an automated clustering for the detection and exact quantification of cortical thickness alterations in first episode schizophrenia. METHODS A group of 54 patients with first episode schizophrenia according to DSM-IV and 54 age and gender matched healthy control subjects were included. All participants underwent high-resolution T1-weighted MRI scans on a 1.5 T scanner. Cortical thickness was estimated as the distance between the gray-white matter border and the pial surface using an automated computerized algorithm (Freesurfer Software). Statistical cortical maps were created to estimate differences of cortical thickness between groups based on this entire cortex analysis. RESULTS Significant cortical thinning was observed in first episode schizophrenia patients relative to controls in a number of cortical areas including the dorsolateral and frontopolar cortices, the anterior cingulate cortex, a ventrolateral-orbitofrontal cluster, as well as the superior temporal cortices and superior parietal lobe. Cortical thinning within these regions was on average 4.4-5.7% with strongest reductions in orbitofrontal regions (7.1%). CONCLUSIONS The present findings suggest widespread reduction of cortical thickness, mostly in heteromodal cortices of fronto-temporal networks to be present at an early stage of schizophrenia. Taken together, the present morphometric data in first episode schizophrenia provide further evidence for potential neurodevelopmental deficits and disruption of cortical maturation in this disorder.

Structural brain alterations in patients with major depressive disorder and high risk for suicide: Evidence for a distinct neurobiological entity?

Major depressive disorder (MDD) is associated with a considerably increased risk for suicide. There is evidence to suggest that a predisposition to suicidal behavior may exist which is independent of the disorder itself. Furthermore, suicide attempters with mood disorders have an up to sixfold higher rate of suicidal behavior in first-degree relatives than non-suicidal patients. Genetic and nongenetic factors may play a role in the familial transmission of suicidal behavior. One of these factors may be neurobiological alterations, the knowledge about which is still limited. The main goal was therefore to study morphometric brain abnormalities in the hypothesized fronto-limbic network in depressed patients with high risk for suicide in contrast to non-high risk depressed patients. 15 patients with MDD and with own suicidal behavior and/or with suicidal behavior in first-degree relatives defined as a high risk group, 15 depressed patients with non-high risk for suicide and 30 matched healthy controls participated in the study. We applied the voxel-based morphometry protocol to structural T1-weighted volumes. Patients with high risk for suicide showed significantly decreased gray matter density in a fronto-striato-limbic network in contrast to matched healthy controls and in caudate and rostral anterior cingulate cortex in contrast to non-high risk patients. In the latter patient group no significant gray matter alterations were detected. This new finding provides evidence for structural brain alterations in depressed patients with high risk for suicide in a brain network strongly involved in emotional and motivational control reflecting a potentially distinct neurobiological entity.

The special involvement of the rostrolateral prefrontal cortex in planning abilities: An event-related fMRI study with the Tower of London paradigm

Planning abilities are essential for the successful management of everyday life activities. Although several neuroimaging studies provide evidence that the prefrontal cortex is crucially involved in planning, the differential roles of its subregions are still a matter of debate. The aim of this study was to investigate the neural correlates of planning by focusing on the functional differentiation between the dorsolateral and rostrolateral prefrontal cortex using the Tower of London (ToL) task and a parametric event-related functional MRI design. In order to control for activations unspecific to planning, two control conditions were presented, which were matched for the length of single events in the ToL task. Seventeen right-handed healthy subjects participated in this study. All statistics were reported with corrections for multiple comparisons (p < 0.05). Compared to control conditions, activations in the ToL task were observed in the dorsolateral prefrontal cortex bilaterally, the right ventrolateral and left rostrolateral prefrontal cortex along with the thalamus, as well as in the parietal and premotor cortex bilaterally. Task complexity dependent analyses revealed that only the left rostrolateral prefrontal cortex showed a BOLD signal increase over the four planning levels, which could not be observed in the control conditions. Hence, current findings suggest that planning involves an extensive fronto-parieto-thalamic network. Within this network, the rostrolateral prefrontal cortex seems to be the only region that is exclusively reactive to planning specific processes, which we described in terms of simultaneous monitoring of internally generated and externally presented information.

Fronto-cingulate effective connectivity in major depression: a study with fMRI and dynamic causal modeling.

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 (Wagner et al., 2006). 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.

Fronto-Cingulate Effective Connectivity in Obsessive Compulsive Disorder: A Study With fMRI and Dynamic Causal Modeling

Evidence suggests that obsessive compulsive disorder (OCD) is associated with an overactive error control system. A key role in error detection and control has been ascribed to the fronto‐cingulate system. However, the exact functional interplay between the single components of this network in OCD is largely unknown. Therefore, the present study combined a univariate data analysis and effective connectivity analysis using dynamic causal modeling (DCM) to examine error control in 21 patients with OCD and 21 matched healthy controls. All subjects performed an adapted version of the Stroop color‐word task while undergoing fMRI scans. Enhanced activation in the fronto‐cingulate system could be detected in OCD patients during the incongruent task condition. Additionally, task‐related modulation of effective connectivity from the dorsal ACC to left DLPFC was significantly stronger in OCD patients. These findings are consistent with an overactive error control system in OCD subserving suppression of prepotent responses during decision‐making. Hum Brain Mapp, 2010.

Prefrontal cortical thickness in depressed patients with high-risk for suicidal behavior

Major depressive disorder (MDD) is associated with an increased risk for suicide. There is considerable evidence that a predisposition to suicidal behavior may exist which is independent of the MDD itself. Recent studies suggest a familial transmission of the diathesis for suicidal behavior, reflected in the observation of suicide aggregation in families and higher rate of suicidal behavior in first-degree relatives of suicide attempters with MDD. One of these transmission factors may be neurobiological alterations. The main goal of the present study was therefore to study abnormalities in cortical thickness in the hypothesized fronto-cingulate network in depressed patients with high risk for suicide. 15 MDD patients with documented own suicidal behavior and/or with suicidal behavior in first-degree relatives (high risk group), 15 depressed patients with non-high risk for suicide and 30 matched healthy controls participated in the study. Using an automated surface based approach (FreeSurfer) structural T1-weighted volumes were analyzed for differences in cortical thickness on a node by node basis covering the entire cortex. Patients with high risk for suicide showed significantly thinner cortex in the left dorsolateral, ventrolateral prefrontal cortex and the anterior cingulate in contrast to non-high risk patients. Together with previous morphometric results of our group, this new finding provides strong evidence for structural brain alterations in depressed patients with high risk for suicide in the fronto-cingulo-striatal network, which is strongly involved in reward processing and behavioral/emotional control. This alteration may constitute the neurobiological basis for an increased predisposition to suicidal behavior.

Inefficient Executive Cognitive Control in Schizophrenia Is Preceded by Altered Functional Activation during Information Encoding: An fMRI Study.

Working memory deficits are a core feature of schizophrenia. Previous working memory studies suggest a load dependent storage deficit. However, explicit studies of higher executive working memory processes are limited. Moreover, few studies have examined whether subcomponents of working memory such as encoding and maintenance of information are differentially affected by these deficits. Therefore, the aim of the present study was to examine the neural substrates of working memory subprocesses requiring stimulus encoding, maintenance and higher executive processing. Using functional magnetic resonance imaging a modified Sternberg working memory task involving verbal stimulus material was applied. The event-related design enabled the segregation of encoding, active maintenance and executive manipulation of information. Forty-one patients with schizophrenia and 41 healthy subjects were included. Relative to normal controls, schizophrenic patients demonstrated a significantly stronger activation pattern in a fronto-parietal network during executive information manipulation. Additionally, significant relative hypoactivity was detectable in the thalamus. Conversely, during stimulus encoding the patients demonstrated lower activation relative to controls in the prefrontal cortex and the anterior cingulate gyrus. The present findings indicate a pronounced prefrontal functional hyperactivation within the neural network subserving higher executive working memory control processes in schizophrenia. Moreover, they suggest that these altered activations during executive control are related to a preceding abnormality of information encoding. During encoding, a reduced activation in mainly dorsolateral prefrontal and anterior cingulate regions was observed. These results could be explained by increased top-down control processing from prefrontal cortex as a compensation for functional deficits occurring during encoding.

Within-patient correspondence of amyloid-β and intrinsic network connectivity in Alzheimer’s disease

The cortical distribution of amyloid-β plaques in Alzheimer’s disease strikingly resembles frontal-parietal intrinsic functional connectivity networks. Using a novel method to trace the distribution of amyloid-β plaques within single patients, Myers et al. reveal a marked negative effect on intrinsic connectivity in several networks that have not typically been investigated.

Temporal changes in neural activation during practice of information retrieval from short-term memory: An fMRI study

Several findings indicate that practice in working memory tasks leads to signal decreases in task-relevant regions. However, the precise dynamics underlying these signal decreases and how they are correlated with improvements in behavioral performance are still matters of debate. We used functional magnetic resonance imaging (fMRI) to assess the cerebral correlates of the practice-related transition from controlled to automatic processing for the retrieval of information maintained in working memory storage. Exponential signal decreases and increases were modeled as covariates of interest. In addition, a bivariate regression analysis on the change in BOLD signal for two a priori hypothesized prefrontal regions (VLPFC, DLPFC) and the change in behavioral performance was conducted to examine the relationship between practice-related changes in cerebral activation and performance. We found exponential practice-related signal decreases mainly in the right superior frontal gyrus/DLPFC (BA 8/9/46), the middle frontal gyrus bilaterally (BA 10/11), the left precentral gyrus (BA 4/6) and the dorsal part of the right anterior cingulate cortex (BA 32). An exponential signal increase was detectable in the posterior cingulate cortex adjacent to the corpus callosum. In addition, there was a correlation between the practice-related change in BOLD signal in the DLPFC (BA 8/9) and the practice-related change in behavioral performance. These results suggest that the transition from controlled to automatic working memory processing is associated with exponential signal decreases in task-relevant regions. The temporal changes in brain activation patterns could be attributed to enhanced efficiency of information processing as a result of cognitive practice.