Effects of rivastigmine on visual attention in subjects with amnestic mild cognitive impairment: A serial functional MRI activation pilot-study.

A pilot study to investigate the effects of rivastigmine on the brain activation pattern due to visual attention tasks in a group of amnestic Mild Cognitive Impaired patients (aMCI). The design was an initial three-month double blind period with a rivastigmine and placebo arms, followed by a nine-month open-label period. All patients underwent serial functional magnetic resonance imaging (fMRI) at baseline, and after three and six months of follow-up. Primary endpoint was the effect of rivastigmine on functional brain changes during visual attention (face and location matching) tasks. There were five in the rivastigmine arm and two in the placebo arm. The face matching task showed higher activation of visual areas after three months of treatment but no differences compared to baseline at six months. The location matching task showed a higher activation along the dorsal visual pathway at both three and six months follow ups. Treatment with rivastigmine demonstrates a significant effect on brain activation of the dorsal visual pathway during a location matching task in patients with aMCI. Our data support the potential use of task fMRI to map specific treatment effects of cholinergic drugs during prodromal stages of Alzheimer's disease (AD).

Neurobiological underpinnings of shame and guilt: a pilot fMRI study.

In this study, a functional magnetic resonance imaging paradigm originally employed by Takahashi et al. was adapted to look for emotion-specific differences in functional brain activity within a healthy German sample (N = 14), using shame- and guilt-related stimuli and neutral stimuli. Activations were found for both of these emotions in the temporal lobe (shame condition: anterior cingulate cortex, parahippocampal gyrus; guilt condition: fusiform gyrus, middle temporal gyrus). Specific activations were found for shame in the frontal lobe (medial and inferior frontal gyrus), and for guilt in the amygdala and insula. This is consistent with Takahashi et al.'s results obtained for a Japanese sample (using Japanese stimuli), which showed activations in the fusiform gyrus, hippocampus, middle occipital gyrus and parahippocampal gyrus. During the imagination of shame, frontal and temporal areas (e.g. middle frontal gyrus and parahippocampal gyrus) were responsive regardless of gender. In the guilt condition, women only activate temporal regions, whereas men showed additional frontal and occipital activation as well as a responsive amygdala. The results suggest that shame and guilt share some neural networks, as well as having individual areas of activation. It can be concluded that frontal, temporal and limbic areas play a prominent role in the generation of moral feelings.

Is evaluation of humorous stimuli associated with frontal cortex morphology? A pilot study using facial micro-movement analysis and MRI.

Humour involves the ability to detect incongruous ideas violating social rules and norms. Accordingly, humour requires a complex array of cognitive skills for which intact frontal lobe functioning is critical. Here, we sought to examine the association of facial expression during an emotion inducing experiment with frontal cortex morphology in healthy subjects. Thirty-one healthy male subjects (mean age: 30.8±8.9 years; all right-handers) watching a humorous movie ("Mr. Bean") were investigated. Markers fixed at certain points of the face emitting high-frequency ultrasonic signals allowed direct measurement of facial movements with high spatial-temporal resolution. Magnetic resonance images of the frontal cortex were obtained with a 1.5-T Magnetom using a coronar T2- and protondensity-weighted Dual-Echo-Sequence and a 3D-magnetization-prepared rapid gradient echo (MPRAGE) sequence. Volumetric analysis was performed using BRAINS. Frontal cortex volume was partly associated with slower speed of "laughing" movements of the eyes ("genuine" or Duchenne smile). Specifically, grey matter volume was associated with longer emotional reaction time ipsilaterally, even when controlled for age and daily alcohol intake. These results lend support to the hypothesis that superior cognitive evaluation of humorous stimuli - mediated by larger prefrontal grey and white matter volume - leads to a measurable reduction of speed of emotional expressivity in normal adults.

Anterior cingulum volumetry, auditory P300 in schizophrenia with negative symptoms.

The anterior cingulate cortex (ACC) is located at the rostum of the corpus callosum and involved in both cognitive and emotional brain processes. It has been suggested to be involved in P300 event-related potential generation. A large sample of schizophrenia inpatients and controls was examined in order to assess the potential relationship between ACC volumes and P300 characteristics in patients with more pronounced negative symptoms. In 50 male schizophrenia patients and 50 matched controls, auditory P300 and structural magnetic resonance imaging volume measurements of the ACC were obtained. Patients' negative symptoms were assessed using the PANSS (Positive and Negative Syndrome Scale). Volumetry of ACC subregions revealed a volume reduction in patients with schizophrenia compared with controls in right hemispheric rostral ACC subregions that were most pronounced in more negative schizophrenia patients. There was a positive correlation between PZ P300 amplitude and total ACC volume in the right hemisphere in schizophrenia patients with less negative symptoms. The results support the assumption that structural changes of the ACC are more pronounced in subgroups of schizophrenia patients with more negative psychopathology. In addition, while right hemisphere ACC volumes significantly differ between schizophrenia subgroups, combining measures of event-related potential (ERP) and ACC volumetry does not add additional information.

Multicentre variability of MRI-based medial temporal lobe volumetry in Alzheimer's disease.

Magnetic resonance imaging (MRI)-based volumetry of medial temporal lobe regions is among the best established biomarker candidates of Alzheimer's disease (AD) to date. This study assessed the effect of multicentre variability of MRI-based hippocampus and amygdala volumetry on the discrimination between patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI) and on the association of morphological changes with ApoE4 genotype and cognition. We studied 113 patients with clinically probable AD and 150 patients with amnestic MCI using high-resolution MRI scans obtained at 12 clinical sites. We determined effect sizes of group discrimination and random effects linear models, considering multicentre variability. Hippocampus and amygdala volumes were significantly reduced in AD compared with MCI patients using data pooled across centres. Multicentre variability did not significantly affect the power to detect a volume difference between AD and MCI patients. Among cognitive measures, delayed recall of verbal and non-verbal material was significantly correlated with hippocampus and amygdala volumes. Amygdala and hippocampus volumes were not associated with ApoE4 genotype in AD or MCI. Our data indicate that multicentre acquisition of MRI data using manual volumetry is reliable and feasible for cross-sectional diagnostic studies, and they replicate essential findings from smaller scale monocentre studies.

Altered brain activation during a verbal working memory task in subjects with amnestic mild cognitive impairment.

In subjects with mild cognitive impairment (MCI), memory disorders indicate a high risk for conversion to Alzheimer's disease (AD). The objective of this study was to delineate the differences in brain activation between amnestic MCI and age-matched healthy controls (HC) during a verbal working memory task. The verbal working memory task was a delay match to sample design. Brain activation was measured using functional magnetic resonance imaging. There were 8 subjects in each group and were matched for performance. The task was analyzed as an event-related design. Group differences were calculated using Analysis of Covariance (ANCOVA) with statistical significance at p<0.05 corrected. Both groups activated a wide network in the posterior and frontal areas of the brain. There was higher activation in the parietal and frontal lobes in the MCI compared to the HC during the maintenance phase. There were no areas in the HC that activated higher than the MCI subjects. Response time in the task in the HC group was correlated to the left hippocampus during encoding phase and to the parietal and frontal areas during the recall phase. In the MCI group, there was strong correlation to the inferior and middle temporal gyrii during encoding, the middle frontal gyrus during the maintenance phase, and hippocampus during recall phase. The activation differences between groups may be compensatory mechanisms within the MCI group for the effects of the putative AD neuropathology. This has been the first study that has examined verbal working memory in MCI.

Functional neuroimaging of duration discrimination on two different time scales.

Analyses of neural mechanisms of duration processing are essential for the understanding of psychological phenomena which evolve in time. Different mechanisms are presumably responsible for the processing of shorter (below 500 ms) and longer (above 500 ms) events but have not yet been a subject of an investigation with functional magnetic resonance imaging (fMRI). In the present study, we show a greater involvement of several brain regions - including right-hemispheric midline structures and left-hemispheric lateral regions - in the processing of visual stimuli of shorter as compared to longer duration. We propose a greater involvement of lower-level cognitive mechanisms in the processing of shorter events as opposed to higher-level mechanisms of cognitive control involved in longer events.

Differences in hippocampal volume between major depression and schizophrenia: a comparative neuroimaging study.

Several studies have demonstrated that structural brain change is detectable in the hippocampus in both patients, with schizophrenia and major depression. Only few studies, however, compared both clinical disease entities directly and no larger study has tried to take different disease stages into account. The objectives of this study are to investigate whether hippocampal volumes are reduced in patients with schizophrenia and those with major depression with the same duration of illness compared to healthy controls and to assess further changes at different disease stages. A total of 319 inpatients and healthy controls were enrolled and investigated with magnetic resonance imaging (MRI). Hippocampal volumes were measured using the segmentation software BRAINS. Bilateral hippocampal volume reductions were detected in both schizophrenic and depressed patients compared to healthy control (HC) subjects. Although younger, schizophrenic (SZ) patients showed in their MRI scans significant bilaterally reduced hippocampal volumes compared to patients with major depression. Although the hippocampal reductions were similar at the onset of symptomatic manifestation of both diseases, there was a further significant reduction of the left hippocampus in the recurrently ill SZ subgroup. The data suggest rather dynamic structural brain alterations in schizophrenia compared to major depression. Here, the presented application of the comparative neuroscience approach, by the use of large neuroimaging MRI databases, seems highly valuable. In the field of psychiatry, with its still controversial operationalized descriptive diagnostic entities, the cross-nosological approach provides a helpful tool to better elucidate the still unknown brain pathologies and their underlying molecular mechanisms beyond a single nosological entity.

Alzheimer disease: functional abnormalities in the dorsal visual pathway.

PURPOSE: To evaluate whether patients with Alzheimer disease (AD) have altered activation compared with age-matched healthy control (HC) subjects during a task that typically recruits the dorsal visual pathway. MATERIALS AND METHODS: The study was performed in accordance with the Declaration of Helsinki, with institutional ethics committee approval, and all subjects provided written informed consent. Two tasks were performed to investigate neural function: face matching and location matching. Twelve patients with mild AD and 14 age-matched HC subjects were included. Brain activation was measured by using functional magnetic resonance imaging. Group statistical analyses were based on a mixed-effects model corrected for multiple comparisons. RESULTS: Task performance was not statistically different between the two groups, and within groups there were no differences in task performance. In the HC group, the visual perception tasks selectively activated the visual pathways. Conversely in the AD group, there was no selective activation during performance of these same tasks. Along the dorsal visual pathway, the AD group recruited additional regions, primarily in the parietal and frontal lobes, for the location-matching task. There were no differences in activation between groups during the face-matching task. CONCLUSION: The increased activation in the AD group may represent a compensatory mechanism for decreased processing effectiveness in early visual areas of patients with AD. The findings support the idea that the dorsal visual pathway is more susceptible to putative AD-related neuropathologic changes than is the ventral visual pathway.

Neuroanatomical correlates of different vulnerability states for psychosis and their clinical outcomes.

BACKGROUND: Structural brain abnormalities have been described in individuals with an at-risk mental state for psychosis. However, the neuroanatomical underpinnings of the early and late at-risk mental state relative to clinical outcome remain unclear. AIMS: To investigate grey matter volume abnormalities in participants in a putatively early or late at-risk mental state relative to their prospective clinical outcome. METHOD: Voxel-based morphometry of magnetic resonance imaging data from 20 people with a putatively early at-risk mental state (ARMS-E group) and 26 people with a late at-risk mental state (ARMS-L group) as well as from 15 participants with at-risk mental states with subsequent disease transition (ARMS-T group) and 18 participants without subsequent disease transition (ARMS-NT group) were compared with 75 healthy volunteers. RESULTS: Compared with healthy controls, ARMS-L participants had grey matter volume losses in frontotemporolimbic structures. Participants in the ARMS-E group showed bilateral temporolimbic alterations and subtle prefrontal abnormalities. Participants in the ARMS-T group had prefrontal alterations relative to those in the ARMS-NT group and in the healthy controls that overlapped with the findings in the ARMS-L group. CONCLUSIONS: Brain alterations associated with the early at-risk mental state may relate to an elevated susceptibility to psychosis, whereas alterations underlying the late at-risk mental state may indicate a subsequent transition to psychosis.

Decreased activation along the dorsal visual pathway after a 3-month treatment with galantamine in mild Alzheimer disease: a functional magnetic resonance imaging study.

Visual perception has been shown to be altered in Alzheimer disease (AD) patients, and it is associated with decreased cognitive function. Galantamine is an active cholinergic agent, which has been shown to lead to improved cognition in mild to moderate AD patients. This study examined brain activation in a group of mild AD patients after a 3-month open-label treatment with galantamine. The objective was to examine the changes in brain activation due to treatment. There were 2 tasks to visual perception. The first task was a face-matching task to test the activation along the ventral visual pathway, and the second task was a location-matching task to test neuronal function along the dorsal pathway. Brain activation was measured using functional magnetic resonance imaging. There were 5 mild AD patients in the study. There were no differences in the task performance and in the cognitive scores of the Consortium to Establish a Registry for Alzheimer's Disease battery before and after treatment. In the location-matching task, we found a statistically significant decrease in activation along the dorsal visual pathway after galantamine treatment. A previous study found that AD patients had higher activation in the location-matching task compared with healthy controls. There were no differences in activation for the face-matching task after treatment. Our data indicate that treatment with galantamine leads to more efficient visual processing of stimuli or changes the compensatory mechanism in the AD patients. A visual perception task recruiting the dorsal visual system may be useful as a biomarker of treatment effects.

Functional neuroanatomy of CCK-4-induced panic attacks in healthy volunteers.

Experimental panic induction with cholecystokinin tetrapeptide (CCK-4) is considered as a suitable model to investigate the pathophysiology of panic attacks. While only a few studies investigated the brain activation patterns following CCK-4, no data are available on the putative involvement of the amygdala in the CCK-4 elicited anxiety response. We studied the functional correlates of CCK-4-induced anxiety in healthy volunteers by means of functional magnetic resonance imaging (fMRI) and region of interest (ROI) analysis of the amygdala. Sixteen healthy volunteers underwent challenge with CCK-4 compared with placebo in a single-blind design. Functional brain activation patterns were determined for the CCK-4-challenge, the placebo response and anticipatory anxiety (AA). CCK-4-induced anxiety was accompanied by a strong and robust activation (random effects analysis, P < 0.00001, uncorrected for multiple testing) in the ventral anterior cingulate cortex (ACC), middle and superior frontal gyrus, precuneus, middle and superior temporal gyrus, occipital lobe, sublobar areas, cerebellum, and brainstem. In contrast, random effects group analysis for placebo and AA using the same level of significance generated no significant results. Using a more liberal level of significance, activations could be observed in some brain regions such as the dorsal part of the ACC during AA (random effects analysis, P < 0.005). Overall functional responses did not differ between panickers and nonpanickers. Only 5 of 11 subjects showed strong amygdala activation. However, ROI analysis pointed towards higher scores in fear items in these subjects. In conclusion, while overall brain activation patterns are not related to the subjective anxiety response to CCK-4, amygdala activation may be involved in the subjective perception of CCK-4-induced fear.

Depression-related variation in brain morphology over 3 years: effects of stress?

CONTEXT: Results of experimental studies suggest that neuroplastic changes may occur during depressive episodes. These effects have not been confirmed in patients with depression, to our knowledge. OBJECTIVE: To examine changes in the brains of patients with major depression vs those of healthy control subjects. DESIGN: Prospective longitudinal 3-year study. SETTING: Inpatients with major depression were recruited from the Department of Psychiatry and Psychotherapy, Ludwig Maximilians University of Munich, Munich, Germany, and controls were recruited from the local community. PARTICIPANTS: The study included 38 patients with major depression and 30 healthy controls. MAIN OUTCOME MEASURES: High-resolution magnetic resonance imaging was performed at baseline and 3 years later. Voxel-based morphometric measurements were estimated from magnetic resonance images, and psychopathologic findings were assessed at baseline, weekly during the inpatient phase, and then after 1, 2, and 3 years. RESULTS: Compared with controls, patients showed significantly more decline in gray matter density of the hippocampus, anterior cingulum, left amygdala, and right dorsomedial prefrontal cortex. Patients who remitted during the 3-year period had less volume decline than nonremitted patients in the left hippocampus, left anterior cingulum, left dorsomedial prefrontal cortex, and bilaterally in the dorsolateral prefrontal cortex. CONCLUSION: This study supports findings from animal studies of neuroplastic stress-related processes that occur in the hippocampus, amygdala, dorsomedial prefrontal cortex, dorsolateral prefrontal cortex, and anterior cingulum during depressive episodes.

Effect of hippocampal and amygdala volumes on clinical outcomes in major depression: a 3-year prospective magnetic resonance imaging study.

OBJECTIVE: According to the stress-toxicity hypothesis of depression, hippocampal volumes may diminish as the disease progresses. We sought to examine the changes in hippocampal and amygdala volumes at baseline and at 3 years after an acute depressive episode, and the impact of reduced hippocampal volumes on the outcome. METHODS: In a prospective, longitudinal study, we examined the hippocampus and amygdala of 30 inpatients with major depression from the Department of Psychiatry and Psychotherapy and 30 healthy participants from the community (control group) using high-resolution magnetic resonance images at baseline and after 3 years. Psychopathology was assessed at baseline, weekly during the inpatient phase and then after 1, 2 and 3 years. RESULTS: During the 3-year follow-up period, neither hippocampal nor amygdala volumes changed significantly among patients or participants in the control group. However, in the subgroup of patients who took antidepressants over the full 3 years, the left hippocampal volumes increased significantly. Patients with small hippocampal volumes and previous depressive episodes had a worse clinical outcome compared with patients with large hippocampal volumes and previous depressive episodes. CONCLUSION: Overall, our results suggest that a relatively small hippocampal volume may be a vulnerability factor for a bad treatment response in major depression. Subtle changes in hippocampal volumes may be detectable during continuous antidepressant therapy. Such changes may be the result of neuroplastic processes.

Functional abnormalities of the visual processing system in subjects with mild cognitive impairment: an fMRI study.

Subjects with mild cognitive impairment (MCI) have a higher risk of developing Alzheimer's disease compared with healthy controls (HC). Sensory impairment can contribute to the severity of cognitive impairment. We measured the activation changes in the visual system between MCI and HC subjects. There were 16 MCI subjects with either amnestic MCI or multiple-domain+amnestic MCI and an HC group of 19 subjects. There were two tasks: (a) a face matching and (b) a location matching task. Brain activation was measured using functional magnetic resonance imaging. There were no differences in task performance. The HC group selectively activated the ventral and dorsal pathways during the face and location matching tasks, respectively, while the MCI group did not. The MCI group had greater activation than the HC group in the left frontal lobe during the location matching task. There were no areas of increased activation in the HC group compared with the MCI group. The MCI group, as a compensatory mechanism, activated both visual pathways and increased activation in the left frontal lobe during the location matching task compared with the healthy controls. To our knowledge, this is the first study that has examined visual processing in MCI.

Involvement patterns in myotilinopathy and desminopathy detected by a novel neuromuscular whole-body MRI protocol.

Whole-body MRI (WB-MRI) has been successfully applied for oncologic and cardiovascular diagnostics, whereas imaging in myopathies usually employs dedicated protocols restricted to areas of specific interest. In this study, we propose a comprehensive neuromuscular WB-MRI protocol. Eighteen patients with degenerative and inflammatory muscle diseases were included. Whole-body imaging was performed on a 1.5-T MR system using parallel imaging. Examination time was 41:26 min. Coronal and axial T1-weighted and coronal short tau inversion recovery (STIR) sequences of the whole body were acquired. Images were analysed by two radiologists. With this protocol we could detect characteristic involvement patterns in different myofibrillar myopathies (MFMs): Patients with myotilinopathy showed frequent involvement of the rhomboid muscles (4/5), the erector spinae (5/5), the biceps femoris and the semimembranosus (5/5), while the semitendinosus was relatively spared (2/5). In contrast, in desminopathy patients the ilipsoas (3/4), the sartorius, (3/4), the gracilis (3/4) and the semitendinosus (3/4) were frequently involved, while the semimembranosus was spared (1/4). As shown for MFMs, WB-MRI is an appropriate modality to detect fatty infiltration and oedema in skeletal muscles. WB-MRI could be more useful than dedicated examinations for differential diagnosis, muscle biopsy planning and noninvasive follow-up examinations.

White matter alterations in schizophrenic patients with pronounced negative symptomatology and with positive family history for schizophrenia.

BACKGROUND: In recent years, in vivo and post-mortem studies detected structural brain changes in schizophrenia. The aim of our analysis was to investigate potential changes of white matter in schizophrenic patients compared to controls, and the relationship to clinical characteristics. METHODS: Fifty male, right-handed schizophrenic patients who met DSM-IV criteria for schizophrenia were recruited. Fifty right-handed, age- and sex-matched subjects without a psychiatric disorder were enrolled as controls. Volumes of white matter in several brain regions were measured by 1.5 T MRI using a volumetry and segmentation software (BRAINS). Regions of interest including frontal, temporal, parietal, occipital and subcortical areas were determined using Talairach spaces. RESULTS: No significant differences in white matter volumes of total brain tissue and regions of interest were detected between patients and controls. A significant reduction of white matter in parietal cortex of right hemisphere was found in a subgroup of patients with pronounced negative symptoms. Furthermore, patients with first-grade relatives suffering from schizophrenia showed a reduction of subcortical white matter in the right hemisphere. CONCLUSIONS: Our results indicate that subgroups of schizophrenic patients show alterations of white matter in distinct brain regions, including the right parietal lobe.

Anterior cingulate cortex does not differ between patients with major depression and healthy controls, but relatively large anterior cingulate cortex predicts a good clinical course.

The anterior cingulate cortex (ACC) is involved in the regulation of emotion processing, and its volume has been found to be reduced in patients with major depression. Furthermore, larger ACC volumes have been associated with faster symptom improvement under therapy. The aims of the study were to examine whether volumes of the anterior cingulate cortex are altered and are related to the clinical course of major depression. Subjects comprised 78 inpatients with major depression and 78 age-, gender- and handedness- matched healthy volunteers, who were investigated with structural magnetic resonance imaging (MRI). The ACC was subdivided into the subgenual, pre-callosal, rostral-anterior and caudal-anterior ACC. No significant differences were observed for ACC volumes between patients and healthy controls. Left ACC volumes showed a significant negative correlation with the number of hospitalizations. These findings suggest that ACC volumes are not altered in patients with major depression, but that patients with larger ACC have a better clinical outcome than patients with smaller ACC.

Structural correlates of psychopathological symptom dimensions in schizophrenia: a voxel-based morphometric study.

Structural neuroimaging has substantially advanced the neurobiological research of schizophrenia by describing a range of focal brain alterations as possible neuroanatomical underpinnings of the disease. Despite this progress, a considerable heterogeneity of structural findings persists that may reflect the phenomenological diversity of schizophrenia. It is unclear whether the range of possible clinical disease manifestations relates to a core structural brain deficit or to distinct structural correlates. Therefore, gray matter density (GMD) differences between 175 schizophrenic patients (SZ) and 177 matched healthy control subjects (HC) were examined in a three-step approach using cross-sectional and conjunctional voxel-based morphometry (VBM): (1) analysis of structural alterations irrespective of symptomatology; (2) subdivision of the patient sample according to a three-dimensional factor model of the PANSS and investigation of structural differences between these subsamples and healthy controls; (3) analysis of a common pattern of structural alterations present in all patient subsamples compared to healthy controls. Significant GMD reductions in patients compared to controls were identified within the prefrontal, limbic, paralimbic, temporal and thalamic regions. The disorganized symptom dimension was associated with bilateral alterations in temporal, insular and medial prefrontal cortices. Positive symptoms were associated with left-pronounced alterations in perisylvian regions and extended thalamic GMD losses. Negative symptoms were linked to the most extended alterations within orbitofrontal, medial prefrontal, lateral prefrontal and temporal cortices as well as limbic and subcortical structures. Thus, structural heterogeneity in schizophrenia may relate to specific patterns of GMD reductions that possibly share a common prefrontal-perisylvian pattern of structural brain alterations.

Influence of trait anxiety on inhibitory control in alcohol-dependent patients: simultaneous acquisition of ERPs and BOLD responses.

Alcohol-dependence is often associated with comorbid psychiatric symptoms. However, the results concerning the influence of these symptoms on cognitive functioning in alcoholism are still inconsistent. The aim of this study was to determine performance monitoring in healthy volunteers and alcohol-dependent patients, and to assess the influence of trait anxiety on these processes. Sixteen healthy volunteers and 16 detoxified alcohol-dependent patients completed an auditory go/nogo paradigm. Functional magnetic resonance imaging, event-related potentials and behavioral data were acquired simultaneously. The patients were classified by median split based on level of self-rated trait anxiety (state-trait anxiety inventory; STAI). The results showed no significant differences regarding inhibition-associated electrophysiological and behavioral responses between alcohol-dependent patients with high-trait anxiety scores and alcohol-addicts with low-STAI scores. However, the functional MRI data revealed elevated activations during the response inhibition task especially in the middle frontal gyrus (BA 6/9), the superior frontal gyrus (BA 6/8/9) and the right inferior frontal gyrus, as well as temporo-parietal brain regions in patients with high-trait anxiety compared to non-anxious alcohol-addicts. Patients and healthy controls showed comparable results with regard to neural and behavioral responses. These results suggest that inhibitory control capacities of alcohol-dependent patients are not consistent: alcohol-addicts with high-trait anxiety ratings showed elevated neural responses compared to patients without any comorbid psychiatric symptoms. This may indicate that comorbid psychiatric symptoms need to be considered when assessing brain responses in alcohol-dependent patients.