Bernhard W. Müller

Cortical Activation to Auditory Mismatch Elicited by Frequency Deviant and Complex Novel Sounds: A PET Study

The analysis of auditory deviant events outside the focus of attention is a fundamental capacity of human information processing and has been studied in experiments on Mismatch Negativity (MMN) and the P3a component in evoked potential research. However, generators contributing to these components are still under discussion. Here we assessed cortical blood flow to auditory stimulation in three conditions. Six healthy subjects were presented with standard tones, frequency deviant tones (MMN condition), and complex novel sounds (Novelty condition), while attention was directed to a nondemanding visual task. Analysis of the MMN condition contrasted with thestandard condition revealed blood flow changes in the left and right superior temporal gyrus, right superior temporal sulcus and left inferior frontal gyrus. Complex novel sounds contrasted with the standard condition activated the left superior temporal gyrus and the left inferior and middle frontal gyrus. A small subcortical activation emerged in the left parahippocampal gyrus and an extended activation was found covering the right superior temporal gyrus. Novel sounds activated the right inferior frontal gyrus when controlling for deviance probability. In contrast to previous studies our results indicate a left hemisphere contribution to a frontotemporal network of auditory deviance processing. Our results provide further evidence for a contribution of the frontal cortex to the processing of auditory deviance outside the focus of directed attention.

Mismatch negativity results from bilateral asymmetric dipole sources in the frontal and temporal lobes

The event-related potential (ERP) reflecting auditory change detection (mismatch negativity, MMN) registers automatic selective processing of a deviant sound with respect to a working memory template resulting from a series of standard sounds. Controversy remains whether MMN can be generated in the frontal as well as the temporal cortex. Our aim was to see if frontal as well as temporal lobe dipoles could explain MMN recorded after pitch-deviants (Pd-MMN) and duration deviants (Dd-MMN). EEG recordings were taken from 32 sites in 14 healthy subjects during a passive 3-tone oddball presented during a simple visual discrimination and an active auditory discrimination condition. Both conditions were repeated after one month. The Pd-MMN was larger, peaked earlier and correlated better between sessions than the Dd-MMN. Two dipoles in the auditory cortex and two in the frontal lobe (left cingulate and right inferior frontal cortex) were found to be similarly placed for Pd- and Dd-MMN, and were well replicated on retest. This study confirms interactions between activity generated in the frontal and auditory temporal cortices in automatic attention-like processes that resemble initial brain imaging reports of unconscious visual change detection. The lack of interference between sessions shows that the situation is likely to be sensitive to treatment or illness effects on fronto-temporal interactions involving repeated measures.

A comparison of psychological and pharmacological treatment of pediatric migraine

A comparison was carried out of the efficacy of psychological and drug treatments for children with migraine. Forty-three children aged between 8 and 16 years (mean age: 11.3 years) who suffered from migraine received either progressive relaxation or cephalic vasomotor feedback, both with stress management training, or metoprolol, a beta-blocker. Psychological treatment was administered in ten sessions lasting six weeks and the drug treatment lasted ten weeks. Relaxation and stress management training reduced the headache index (frequency x intensity of headache episodes), more effectively than metoprolol with cephalic vasomotor feedback and stress management training in between. An overall improvement over time was found with regard to frequency and intensity of headache episodes and analgesics intake. When comparing pre- to post-treatment data, children treated with relaxation training improved significantly in headache frequency and intensity, whereas those treated with cephalic vasomotor feedback improved significantly in headache frequency and duration as well as mood. The clinical improvement was stable at an 8-months follow-up.

Disentangling Structural Brain Alterations Associated With Violent Behavior From Those Associated With Substance Use Disorders

CONTEXT Studies aimed at identifying structural brain alterations associated with persistent violent behavior or psychopathy have not adequately accounted for a lifetime history of substance misuse. Thus, alterations in gray matter (GM) volume that have been reported to be correlates of violent behavior and/or psychopathy may instead be related to lifelong substance use disorders (SUDs). OBJECTIVE To identify alterations in GM volume associated with violent behavior and those associated with lifelong SUDs. DESIGN Cross-sectional study. SETTING Participants were recruited from penitentiaries, forensic hospitals, psychiatric outpatient services, and communities in Germany. Structural magnetic resonance imaging was performed at a university hospital. PARTICIPANTS Four groups of men were compared: 12 men with SUDs who exhibited violent behavior (hereafter referred to as violent offenders), 12 violent offenders without SUDs, 13 men with SUDs who did not exhibit violent behavior (hereafter referred to as nonoffenders), and 14 nonoffenders without SUDs. MAIN OUTCOME MEASURES Voxel-based morphometry was used to analyze high-resolution magnetic resonance imaging scans. Assessments of mental disorders, psychopathy (using the Psychopathy Checklist-Screening Version), aggressive behavior, and impulsivity were conducted by trained clinicians. RESULTS Compared with nonoffenders, violent offenders presented with a larger GM volume in the amygdala bilaterally, the left nucleus accumbens, and the right caudate head and with less GM volume in the left insula. Men with SUDs exhibited a smaller GM volume in the orbitofrontal cortex, ventromedial prefrontal cortex, and premotor cortex than did men without SUDs. Regression analyses indicated that the alterations in GM volume that distinguished the violent offenders from nonoffenders were associated with psychopathy scores and scores for lifelong aggressive behavior. The GM volumes of the orbitofrontal cortex and prefrontal cortex that distinguished the men with SUDs from the men without SUDs were correlated with scores for response inhibition. CONCLUSIONS These findings suggest that a greater GM volume in the mesolimbic reward system may be associated with violent behavior and that reduced GM volumes in the prefrontal cortex, orbitofrontal cortex, and premotor area characterize men with SUDs.

The intensity dependence of the auditory evoked N1 component as a predictor of reponse to Citalopram treatment in patients with major depression

The intensity dependence of the auditory evoked N1 ERP component (IDAP) has been suggested as an indicator of central serotonergic neurotransmission with relevance to pharmacological treatment. We report the results of a study evaluating the IDAP in 16 in-patients fulfilling DSM-IV criteria for major depressive episode in the course of treatment with the SSRI Citalopram. Our data revealed a significant correlation between the intensity slopes of the N1 amplitude prior to Citalopram treatment and treatment response: patients with higher intensity slopes of N1 amplitude showed a significantly stronger decrease of HDRS-Score after Citalopram treatment than patients within the lower intensity slope ranges. Our results indicate an association of N1 amplitude intensity dependence with response to antidepressant treatment with Citalopram.

Neuropsychological assessment of adult patients with attention-deficit/hyperactivity disorder

Adults with persistent attention-deficit/hyperactivity disorder (ADHD) may show cognitive deficits as compared to healthy control subjects. The aim of this study was to compare a sample of adult outpatients with ADHD on medication to healthy controls on a comprehensive neuropsychological assessment battery. Thirty adults with ADHD under stable psychopharmacological treatment and 27 healthy controls matched for age, gender, and IQ were assessed with ten tests measuring performance with regard to attention, memory, executive function, and fine motor control. Lower performance in patients as compared to controls was found in tests of verbal and visual memory, speed of visuo-motor search, set shifting, and divided attention. Indicators of response inhibition and simple response speed were less affected. Adults with ADHD show indicators of lowered cognitive performance under medication. These are related more to memory and attention under high mental load than to response inhibition or simple attention or motor performance.

Treatment of acute alcohol withdrawal with gabapentin: results from a controlled two-center trial.

A few case reports and data from animal experiments point to a possible efficacy of gabapentin (GP) in the treatment of alcohol withdrawal syndrome (AWS). Because of ethical considerations, the efficacy of GP in acute AWS was tested in an add-on fashion to clomethiazole (CLO). Given that the symptom-triggered amount of CLO required to limit AWS within the first 24 hours is related to the severity of AWS, we tested this amount of CLO during placebo (P) or GP (400 mg qid) under double blind, randomized conditions. Sixty-one patients (P = 29/GP = 32) suffering from alcohol dependence (ICD-10) and without any other psychiatric condition or psychotropic medication were included. The groups were not significantly different in baseline characteristics (eg, demographic data, severity of AWS). Both ITT and completer analyses revealed no significant differences between the groups considering the primary effectiveness measure: amount of CLO required in the first 24 hours (P = 6.1 ± 5.4/GP = 6.2 ± 4.7 capsules). In addition, premature discontinuations (P = 3/GP = 2) and decreases in Mainz Alcohol Withdrawal Scores were not significantly different in the first 48 hours of AWS (secondary effectiveness measures). Tolerability of combined CLO/GP was studied throughout the whole treatment comprising a 5-day lasting reduction part subsequent to the first 48 hours. Throughout the whole 7-day treatment a total of 5 and 2 patients dropped out and 6 and 5 patients reported adverse clinical events in the P and GP groups, respectively. All together, GP (400 mg qid) was no better than P in saving initial consumption of CLO or decreasing initial Mainz Alcohol Withdrawal Scores suggesting that GP was ineffective in the management of acute AWS in this model. The combination of GP and CLO was safe.

Impulsivity-related brain volume deficits in schizophrenia-addiction comorbidity

Despite a high prevalence of schizophrenia patients with comorbid substance abuse, little is known about possible impacts on the brain. Hence, our goal was to determine whether addicted and non-addicted schizophrenic patients suffer from different brain deficits. We were especially interested to determine if grey matter volumes were affected by impulsivity. We hypothesized that (comorbid) substance abuse would be associated with enhanced impulsivity and that this enhanced impulsivity would be related to grey matter volume deficits in prefrontal areas. We employed a voxel-based morphometry approach as well as neuropsychological assessment of executive functions and trait impulsivity in 51 participants (age range 23-55). The schizophrenia group comprised 24 patients (12 patients with paranoid schizophrenia and 12 with additional comorbid substance use disorders). The comparison group comprised 27 non-schizophrenic individuals, matched by age and education (14 healthy individuals and 13 patients with substance use disorders). Total grey matter volume deficits were found in all patient groups as compared with healthy controls but were largest (~8%) in both addicted groups. While grey matter volume losses in lateral orbitofrontal and temporal regions were affected by schizophrenia, volume decreases of the medial orbitofrontal, anterior cingulate and frontopolar cortex were associated with addiction. Compared with non-addicted schizophrenics, comorbid patients showed significant volume decreases in anterior cingulate, frontopolar and superior parietal regions. Additionally, they showed an increased non-planning impulsivity that was negatively related to grey matter volumes in the same regions, except for parietal ones. The present study indicates severe grey matter volume and functional executive deficits in schizophrenia, which were only partially exacerbated by comorbid addiction. However, the relationship between non-planning impulsivity and anterior cingulate and frontopolar grey matter volumes points to a specific structure-function relationship that seems to be impaired in schizophrenia-addiction comorbidity.

The precuneus and the insula in self-attributional processes

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.

Vermal atrophy of alcoholics correlate with serum thiamine levels but not with dentate iron concentrations as estimated by MRI

AbstractChronic alcohol consumption is frequently accompanied by cerebellar degeneration. The exact aetiology of alcoholic cerebellar degeneration is still a matter of debate. The aim of the present study was to investigate whether patients with chronic alcohol consumption exhibit a decrease in dentate nuclei intensity as measured by MRI, and if so, whether this decrease correlates with cerebellar atrophy as revealed by MR imaging or with clinical signs of cerebellar ataxia. A decrease in dentate nuclei intensity would indirectly indicate that iron accumulation, and therefore, oxidative stress may play a role in alcoholic cerebellar degeneration.MRI of 45 alcoholics and 44 ageand sex–matched healthy control subjects was performed using a 3D–T1–weighted fast low angle shot (FLASH) echo sequence. Signal intensities of the dentate nuclei and cerebellar white matter were bilaterally measured. Planimetric measurements of cerebellar size were performed using a 3D–T1–weighted magnetization prepared rapid acquisition gradient echo (MPRAGE) sequence.Results demonstrated that dentate nuclei intensity was not significantly decreased in patients with chronic alcohol consumption (mean ± SD signal intensity 65.36 ± 13.0) if compared with control subjects (mean ± SD signal intensity 68.95 ± 9.4) (p = 0.15). Dentate nuclei intensity did not correlate with cerebellar size neither in control subjects nor in alcoholics. In contrast, vitamin B1 level correlated with cerebellar size in alcoholics even if the vitamin B1 concentration was within normal values (r = 0.344, p = 0.028). These results support the view that thiamine deficiency rather than direct neurotoxic effects of alcohol is the main causative factor for the development of alcoholic cerebellar degeneration.