Word recognition memory and serum levels of Borna disease virus specific circulating immune complexes in obsessive-compulsive disorder.

BACKGROUND: Borna disease virus 1 (BoDV-1) is a non-segmented, negative-strand RNA virus that persistently infects mammals including humans. BoDV-1 worldwide occurring strains display highly conserved genomes with overlapping genetic signatures between those of either human or animal origin. BoDV-1 infection may cause behavioral and cognitive disturbances in animals but has also been found in human major depression and obsessive-compulsive disorder (OCD). However, the impact of BoDV-1 on memory functions in OCD is unknown. METHOD: To evaluate the cognitive impact of BoDV-1 in OCD, event-related brain potentials (ERPs) were recorded in a continuous word recognition paradigm in OCD patients (n = 16) and in healthy controls (n = 12). According to the presence of BoDV-1-specific circulating immune complexes (CIC), they were divided into two groups, namely group H (high) and L (low), n = 8 each. Typically, ERPs to repeated items are characterized by more positive waveforms beginning approximately 250 ms post-stimulus. This "old/new effect" has been shown to be relevant for memory processing. The early old/new effect (ca. 300-500 ms) with a frontal distribution is proposed to be a neural correlate of familiarity-based recognition. The late old/new effect (post-500 ms) is supposed to reflect memory recollection processes. RESULTS: OCD patients were reported to show a normal early old/new effect and a reduced late old/new effect compared to normal controls. In our study, OCD patients with a high virus load (group H) displayed exactly these effects, while patients with a low virus load (group L) did not differ from healthy controls. CONCLUSION: These results confirmed that OCD patients had impaired memory recollection processes compared to the normal controls which may to some extent be related to their BoDV-1 infection.

Antiviral treatment perspective against Borna disease virus 1 infection in major depression: a double-blind placebo-controlled randomized clinical trial.

BACKGROUND: Whether Borna disease virus (BDV-1) is a human pathogen remained controversial until recent encephalitis cases showed BDV-1 infection could even be deadly. This called to mind previous evidence for an infectious contribution of BDV-1 to mental disorders. Pilot open trials suggested that BDV-1 infected depressed patients benefitted from antiviral therapy with a licensed drug (amantadine) which also tested sensitive in vitro. Here, we designed a double-blind placebo-controlled randomized clinical trial (RCT) which cross-linked depression and BDV-1 infection, addressing both the antidepressant and antiviral efficacy of amantadine. METHODS: The interventional phase II RCT (two 7-weeks-treatment periods and a 12-months follow-up) at the Hannover Medical School (MHH), Germany, assigned currently depressed BDV-1 infected patients with either major depression (MD; N = 23) or bipolar disorder (BD; N = 13) to amantadine sulphate (PK-Merz®; twice 100 mg orally daily) or placebo treatment, and contrariwise, respectively. Clinical changes were assessed every 2-3 weeks by the 21-item Hamilton rating scale for depression (HAMD) (total, single, and combined scores). BDV-1 activity was determined accordingly in blood plasma by enzyme immune assays for antigens (PAG), antibodies (AB) and circulating immune complexes (CIC). RESULTS: Primary outcomes (≥25% HAMD reduction, week 7) were 81.3% amantadine vs. 35.3% placebo responder (p = 0.003), a large clinical effect size (ES; Cohen's d) of 1.046, and excellent drug tolerance. Amantadine was safe reducing suicidal behaviour in the first 2 weeks. Pre-treatment maximum infection levels were predictive of clinical improvement (AB, p = 0.001; PAG, p = 0.026; HAMD week 7). Respective PAG and CIC levels correlated with AB reduction (p = 0,001 and p = 0.034, respectively). Follow-up benefits (12 months) correlated with dropped cumulative infection measures over time (p < 0.001). In vitro, amantadine concentrations as low as 2.4-10 ng/mL (50% infection-inhibitory dose) prevented infection with human BDV Hu-H1, while closely related memantine failed up to 100,000-fold higher concentration (200 µg/mL). CONCLUSIONS: Our findings indicate profound antidepressant efficacy of safe oral amantadine treatment, paralleling antiviral effects at various infection levels. This not only supports the paradigm of a link of BDV-1 infection and depression. It provides a novel possibly practice-changing low cost mental health care perspective for depressed BDV-1-infected patients addressing global needs. TRIAL REGISTRATION: The trial was retrospectively registered in the German Clinical Trials Registry on 04th of March 2015. The trial ID is DRKS00007649; https://www.drks.de/drks_web/setLocale_EN.do.

Glia in the cytokine-mediated onset of depression: fine tuning the immune response.

Major depressive disorder (MDD) is a mood disorder of multifactorial origin affecting millions of people worldwide. The alarming estimated rates of prevalence and relapse make it a global public health concern. Moreover, the current setback of available antidepressants in the clinical setting is discouraging. Therefore, efforts to eradicate depression should be directed towards understanding the pathomechanisms involved in the hope of finding cost-effective treatment alternatives. The pathophysiology of MDD comprises the breakdown of different pathways, including the hypothalamus-pituitary-adrenal (HPA) axis, the glutamatergic system, and monoaminergic neurotransmission, affecting cognition and emotional behavior. Inflammatory cytokines have been postulated to be the possible link and culprit in the disruption of these systems. In addition, evidence from different studies suggests that impairment of glial functions appears to be a major contributor as well. Thus, the intricate role between glia, namely microglia and astrocytes, and the central nervous system's (CNSs) immune response is briefly discussed, highlighting the kynurenine pathway as a pivotal player. Moreover, evaluations of different treatment strategies targeting the inflammatory response are considered. The immuno-modulatory properties of vitamin D receptor (VDR) suggest that vitamin D is an attractive and plausible candidate in spite of controversial findings. Further research investigating the role of VDR in mood disorders is warranted.

N1 enhancement in synesthesia during visual and audio-visual perception in semantic cross-modal conflict situations: an ERP study.

Synesthesia entails a special kind of sensory perception, where stimulation in one sensory modality leads to an internally generated perceptual experience of another, not stimulated sensory modality. This phenomenon can be viewed as an abnormal multisensory integration process as here the synesthetic percept is aberrantly fused with the stimulated modality. Indeed, recent synesthesia research has focused on multimodal processing even outside of the specific synesthesia-inducing context and has revealed changed multimodal integration, thus suggesting perceptual alterations at a global level. Here, we focused on audio-visual processing in synesthesia using a semantic classification task in combination with visually or auditory-visually presented animated and in animated objects in an audio-visual congruent and incongruent manner. Fourteen subjects with auditory-visual and/or grapheme-color synesthesia and 14 control subjects participated in the experiment. During presentation of the stimuli, event-related potentials were recorded from 32 electrodes. The analysis of reaction times and error rates revealed no group differences with best performance for audio-visually congruent stimulation indicating the well-known multimodal facilitation effect. We found enhanced amplitude of the N1 component over occipital electrode sites for synesthetes compared to controls. The differences occurred irrespective of the experimental condition and therefore suggest a global influence on early sensory processing in synesthetes.

Reduced audiovisual integration in synesthesia--evidence from bimodal speech perception.

Recent research suggests synesthesia as a result of a hypersensitive multimodal binding mechanism. To address the question whether multimodal integration is altered in synesthetes in general, grapheme-colour and auditory-visual synesthetes were investigated using speech-related stimulation in two behavioural experiments. First, we used the McGurk illusion to test the strength and number of illusory perceptions in synesthesia. In a second step, we analysed the gain in speech perception coming from seen articulatory movements under acoustically noisy conditions. We used disyllabic nouns as stimulation and varied signal-to-noise ratio of the auditory stream presented concurrently to a matching video of the speaker. We hypothesized that if synesthesia is due to a general hyperbinding mechanism this group of subjects should be more susceptible to McGurk illusions and profit more from the visual information during audiovisual speech perception. The results indicate that there are differences between synesthetes and controls concerning multisensory integration--but in the opposite direction as hypothesized. Synesthetes showed a reduced number of illusions and had a reduced gain in comprehension by viewing matching articulatory movements in comparison to control subjects. Our results indicate that rather than having a hypersensitive binding mechanism, synesthetes show weaker integration of vision and audition.

Is synesthesia more common in patients with Asperger syndrome?

There is increasing evidence from case reports that synesthesia is more common in individuals with autism spectrum conditions (ASC). Further, genes related to synesthesia have also been found to be linked to ASC and, similar to synaesthetes, individuals with ASC show altered brain connectivity and unusual brain activation during sensory processing. However, up to now a systematic investigation of whether synesthesia is more common in ASC patients is missing. The aim of the current pilot study was to test this hypothesis by investigating a group of patients diagnosed with Asperger Syndrome (AS) using questionnaires and standard consistency tests in order to classify them as grapheme-color synaesthetes. The results indicate that there are indeed many more grapheme-color synaesthetes among AS patients. This finding is discussed in relation to different theories regarding the development of synesthesia as well as altered sensory processing in autism.

Impaired perceptual processing and conceptual cognition in patients with anxiety disorders: a pilot study with the binocular depth inversion paradigm.

The binocular depth inversion test (BDIT) measures a common illusion of visual perception whereby implausible objects are seen as normal, e.g., a hollow face is perceived as a normal, convex face. Such inversion is frequent, especially for objects with a high degree of familiarity. Under normal conditions, cognitive factors apparently override the binocular disparity cues of stereopsis. This internal mechanism of "censorship" of perception, which balances "top-down" and "bottom-up" processes of perception to come to a cognitive coherence, which is congruent to previous experience and concepts, appears to be disturbed in (pro-)psychotic states. The BDIT has been shown to be a sensitive measure of impaired higher visual processing and conceptual cognition common to conditions including schizophrenia, cannabinoid-intoxication, and sleep deprivation but not depression. In this pilot study, we tested the performance of patients with anxiety disorders (ICD-10 F40 and F41) compared to matched controls using the BDIT paradigm. Anxiety patients scored significantly higher on the BDIT than controls, in a range comparable to propsychotic conditions. The findings suggest that anxiety patients could have abnormalities in central perceptual processing, top-down processing (conceptual cognition), and reality testing similar to (pro-)psychotic conditions. Implications of these findings are discussed in relation to therapeutic interventions with anxiety disorders.

Reduced audio-visual integration in synaesthetes indicated by the double-flash illusion.

It has been suggested that synaesthesia is the result of a hyper-sensitive multimodal binding-mechanism. To address the question whether multi-modal integration is altered in synaesthetes in general, grapheme-colour and auditory-visual synaesthetes were studied using the double-flash illusion. This illusion is induced by a single light flash presented together with multiple beep sounds, which is then perceived as multiple flashes. By varying the separation of auditory and visual stimuli, the hypothesis of a widened temporal window of audio-visual integration in synaesthetes was tested. As hypothesised, the results show differences between synaesthetes and controls concerning multisensory integration, but surprisingly other than expected synaesthetes perceive a reduced number of illusions and have a smaller time-window of audio-visual integration compared to controls. This indicates that they do not have a hyper-sensitive binding mechanism. On the contrary, synaesthetes seem to integrate even less than controls between vision and audition.

Mitigation of post-traumatic stress symptoms by Cannabis resin: a review of the clinical and neurobiological evidence.

It is known from clinical studies that some patients attempt to cope with the symptoms of post-traumatic stress disorder (PTSD) by using recreational drugs. This review presents a case report of a 19-year-old male patient with a spectrum of severe PTSD symptoms, such as intense flashbacks, panic attacks, and self-mutilation, who discovered that some of his major symptoms were dramatically reduced by smoking cannabis resin. The major part of this review is concerned with the clinical and preclinical neurobiological evidence in order to offer a potential explanation of these effects on symptom reduction in PTSD. This review shows that recent studies provided supporting evidence that PTSD patients may be able to cope with their symptoms by using cannabis products. Cannabis may dampen the strength or emotional impact of traumatic memories through synergistic mechanisms that might make it easier for people with PTSD to rest or sleep and to feel less anxious and less involved with flashback memories. The presence of endocannabinoid signalling systems within stress-sensitive nuclei of the hypothalamus, as well as upstream limbic structures (amygdala), point to the significance of this system for the regulation of neuroendocrine and behavioural responses to stress. Evidence is increasingly accumulating that cannabinoids might play a role in fear extinction and antidepressive effects. It is concluded that further studies are warranted in order to evaluate the therapeutic potential of cannabinoids in PTSD.

Genuine and drug-induced synesthesia: a comparison.

Despite some principal similarities, there is no systematic comparison between the different types of synesthesia (genuine, acquired and drug-induced). This comprehensive review compares the three principal types of synesthesia and focuses on their phenomenological features and their relation to different etiological models. Implications of this comparison for the validity of the different etiological models are discussed. Comparison of the three forms of synesthesia show many more differences than similarities. This is in contrast to their representation in the literature, where they are discussed in many respects as being virtually similar. Noteworthy is the much broader spectrum and intensity with the typical drug-induced synesthesias compared to genuine and acquired synesthesias. A major implication of the phenomenological comparison in regard to the etiological models is that genuine and acquired synesthesias point to morphological substrates, while drug-induced synesthesia appears to be based on functional changes of brain activity.

Word recognition memory in adults with attention-deficit/hyperactivity disorder as reflected by event-related potentials.

OBJECTIVE: Attention-deficit/hyperactivity disorder (ADHD) is increasingly diagnosed in adults. In this study we address the question whether there are impairments in recognition memory. METHODS: In the present study 13 adults diagnosed with ADHD according to DSM-IV and 13 healthy controls were examined with respect to event-related potentials (ERPs) in a visual continuous word recognition paradigm to gain information about recognition memory effects in these patients. RESULTS: The amplitude of one attention-related ERP component, the N1, was significantly increased for the ADHD adults compared with the healthy controls in the occipital electrodes. The ERPs for the second presentation were significantly more positive than the ERPs for the first presentation. This effect did not significantly differ between groups. CONCLUSION: Neuronal activity related to an early attentional mechanism appears to be enhanced in ADHD patients. Concerning the early or the late part of the old/new effect ADHD patients show no difference which suggests that there are no differences with respect to recollection and familiarity-based recognition processes.

Axis-I comorbidity in female patients with dissociative identity disorder and dissociative identity disorder not otherwise specified.

The aim of this study was to investigate axis-I comorbidity in patients with dissociative identity disorder (DID) and dissociative disorder not otherwise specified (DDNOS). Using the Diagnostic Interview for Psychiatric Disorders, results from patients with DID (n = 44) and DDNOS (n = 22) were compared with those of patients with posttraumatic stress disorder (PTSD) (n = 13), other anxiety disorders (n = 14), depression (n = 17), and nonclinical controls (n = 30). No comorbid disorders were found in nonclinical controls. The average number of comorbid disorders in patients with depression or anxiety was 0 to 2. Patients with dissociative disorders averagely suffered from 5 comorbid disorders. The most prevalent comorbidity in DDNOS and DID was PTSD. Comorbidity profiles of patients with DID and DDNOS were very similar to those in PTSD (high prevalence of anxiety, somatoform disorders, and depression), but differed significantly from those of patients with depression and anxiety disorders. These findings confirm the hypothesis that PTSD, DID, and DDNOS are phenomenologically related syndromes that should be summarized within a new diagnostic category.

Reduced P300 and P600 amplitude in the hollow-mask illusion in patients with schizophrenia.

Illusions provide a useful tool to study the mechanisms by which top-down and bottom-up processes interact in perception. Patients suffering from schizophrenia are not as subject to the hollow-mask illusion as healthy controls, since studies have shown that controls perceive a hollow mask as a normal face, while patients with schizophrenia do not. This insusceptibility to the illusion is indicating a weakened top-down processing in schizophrenia and little is understood about the neurobiology of this phenomenon. We used event-related potentials to investigate the hollow-mask illusion in patients with schizophrenia and healthy controls. We hypothesized that there would be a visible reduction of top-down processing in the patients' group and that this reduction would occur in the late stages of processing. We found significantly decreased amplitudes in the P300 and P600 components in the patients' group, indicating that visual information does not benefit from frontal, parietal or temporal activity for perceiving incoming stimuli. We propose that a deficit in functional connectivity may be responsible for impaired top-down visual processing in schizophrenia. These data further the understanding of the time course of top-down processing in patients with schizophrenia.

Neuronal correlates of ADHD in adults with evidence for compensation strategies--a functional MRI study with a Go/No-Go paradigm.

OBJECTIVE: Response inhibition impairment is one of the most characteristic symptoms of attention-deficit/hyperactivity disorder (ADHD). Thus functional magnetic resonance imaging (fMRI) during a Go/No-Go task seems to be an ideal tool for examining neuronal correlates of inhibitory control deficits in ADHD. Prior studies have shown frontostriatal abnormalities in children and adolescents. The aim of our study was to investigate whether adults with ADHD would still show abnormal brain activation in prefrontal brain regions during motor response inhibition tasks. METHODS: fMRI was used to compare brain activation in 15 untreated adult patients with ADHD and 15 healthy reference volunteers during performance of a Go/No-Go task. RESULTS: In contrast to various other studies with children and adolescents with ADHD, we found no significant difference in the activity of anterior cingulate cortex (ACC) or other frontostriatal structures between ADHD and healthy adults. Significantly enhanced activity was found in the parietal cortex, which is known to play an important role in building up attention. CONCLUSION: We hypothesize that the enhanced activity is due to the ability of adult ADHD patients to compensate their deficits for a short time, which is demonstrated in our study by equal task performance in both groups.

Impaired top-down processes in schizophrenia: a DCM study of ERPs.

Perception is not simply based on a hierarchical organization of the brain; it arises from an interplay between inputs from the environment and internal predictions of these inputs. It is an active process which involves an interaction between bottom-up information coming from the senses and feedback connections coming from higher-order cortical areas. In our experiment, we use the hollow-mask illusion to investigate the strength of top-down processes in schizophrenic patients and healthy controls. By using dynamic causal modelling (DCM) on functional magnetic resonance tomography (fMRI) data, we have presented evidence to suggest that patients with schizophrenia are less constrained by top-down processes during perception (Dima, D., Roiser, J.P., Dietrich, D.E., Bonnemann, C., Lanfermann, H., Emrich, H.M., Dillo, W., 2009. Understanding why patients with schizophrenia do not perceive the hollow-mask illusion using dynamic causal modeling. Neuroimage 46, 1180-1186). In this study, we re-address this issue by using DCM on event-related potentials (ERPs) data. Our aim was to validate our previous findings by conducting the same connectivity analysis--DCM--on data obtained from a different neuroimaging method. Our results confirm our initial hypothesis that top-down influences are constrained in schizophrenia, especially in perceptual tasks that require top-down control, like the hollow-mask illusion.

Asperger's syndrome in adulthood.

INTRODUCTION: Asperger's syndrome is one of the autism spectrum disorders. Affected individuals display considerably impaired capacity for social interaction, unusual special interests, and a tendency towards ritualized behavior. METHODS: The etiology, symptoms, diagnosis, and treatment of Asperger's syndrome in adulthood are outlined on the basis of a selective literature review via Medline and information in relevant reference books. Furthermore, the authors report their personal experience at a special clinic for adults. RESULTS: Asperger's syndrome in adulthood can be diagnosed by thorough anamnesis, heteroanamnesis-with emphasis on childhood-and painstaking clinical examination. The considerable psychosocial impairments affect the patients' professional, social, and private lives. The precise etiology is still unknown, but a multifactorial origin with genetic, neurobiological, and psychosocial components appears probable. Although no specific, empirically tested treatment concepts have yet been established, psychotherapeutic elements (structuring and directive interventions) seem to be helpful, together with pharmacotherapy-if indicated-in the presence of comorbidity. CONCLUSIONS: Asperger's syndrome should be included in the differential diagnosis of adults who display the corresponding symptoms. The etiopathogenesis and treatment of Asperger's syndrome in adulthood should be further investigated.

Prefrontal and anterior cingulate cortex abnormalities in Tourette Syndrome: evidence from voxel-based morphometry and magnetization transfer imaging.

BACKGROUND: Pathophysiological evidence suggests an involvement of fronto-striatal circuits in Tourette syndrome (TS). To identify TS related abnormalities in gray and white matter we used optimized voxel-based morphometry (VBM) and magnetization transfer imaging (MTI) which are more sensitive to tissue alterations than conventional MRI and provide a quantitative measure of macrostructural integrity. METHODS: Volumetric high-resolution anatomical T1-weighted MRI and MTI were acquired in 19 adult, unmedicated male TS patients without co-morbidities and 20 age- and sex-matched controls on a 1.5 Tesla neuro-optimized GE scanner. Images were pre-processed and analyzed using an optimized version of VBM in SPM2. RESULTS: Using VBM, TS patients showed significant decreases in gray matter volumes in prefrontal areas, the anterior cingulate gyrus, sensorimotor areas, left caudate nucleus and left postcentral gyrus. Decreases in white matter volumes were detected in the right inferior frontal gyrus, the left superior frontal gyrus and the anterior corpus callosum. Increases were found in the left middle frontal gyrus and left sensorimotor areas. In MTI, white matter reductions were seen in the right medial frontal gyrus, the inferior frontal gyrus bilaterally and the right cingulate gyrus. Tic severity was negatively correlated with orbitofrontal structures, the right cingulate gyrus and parts of the parietal-temporal-occipital association cortex bilaterally. CONCLUSION: Our MRI in vivo neuropathological findings using two sensitive and unbiased techniques support the hypothesis that alterations in frontostriatal circuitries underlie TS pathology. We suggest that anomalous frontal lobe association and projection fiber bundles cause disinhibition of the cingulate gyrus and abnormal basal ganglia function.

S100B serum levels and word memory processing in remitted major depression as reflected by brain potentials.

OBJECTIVE: Memory processes, as reflected by 'old/new' effects of event-related potentials (ERPs), have been shown to be impaired in depressed patients. This variability might be partly explained by biological factors. S100B is a glial calcium-binding protein with neuroplastic properties; S100B serum levels have been shown to be increased in depressive patients. The pathophysiologic role of S100B in depression, however, is not yet sufficiently understood. METHODS: In the present study, ERPs recorded in a visual continuous word recognition paradigm were therefore investigated in patients with remitted major depression in relation to S100B serum levels. RESULTS: Patients with moderately increased S100B serum levels (n = 6) showed a normal old/new effect in contrast to a reduced old/new effect in patients with normal S100B levels (n = 6) compared to aged-matched controls. CONCLUSIONS: These findings provide evidence of an association between S100B levels and memory processes in patients with recurrent depression and further suggest a neuroprotective role of moderately increased S100B serum levels in the course of affective disorders.

Understanding why patients with schizophrenia do not perceive the hollow-mask illusion using dynamic causal modelling.

Patients suffering from schizophrenia are less susceptible to various visual illusions. For example, healthy participants perceive a hollow mask as a normal face, presumably due to the strength of constraining top-down influences, while patients with schizophrenia do not (Schneider, U., Leweke, F.M., Sternemann, U., Weber, M.M., Emrich, H.M., 1996. Visual 3D illusion: a systems-theoretical approach to psychosis. Eur. Arch. Psychiatry Clin. Neurosci. 246, 256-260; Scheider, U., Borsutzky, M., Seifert, J., Leweke, F.M., Huber, T.J., Rollnik J.D., Emrich, H.M., 2002. Reduced binocular depth inversion in schizophrenic patients. Schizophrenia Research 53, 101-108.; Emrich, H.M., Leweke, F.M., Schneider, U., 1997. Towards a cannabinoid hypothesis of schizophrenia: cognitive impairments due to a dysregulation of the endogenous cannabinoid system. Pharmacol. Biochem. Behav. 56, 803-807). However the neural mechanisms underpinning this effect remain poorly understood. We used functional magnetic resonance imaging to investigate the hollow-mask illusion in schizophrenic patients and healthy controls. The primary aim of this study was to use measures of effective connectivity arising from dynamic causal modelling (DCM) to explain differences in both the perception of the hollow-mask illusion and associated differences in neural responses between patients with schizophrenia and controls, which we hypothesised would be associated with difference in the influences of top-down and bottom-up processes between the groups. Consistent with this explanation, we identified differences between the two groups in effective connectivity. In particular, there was a strengthening of bottom-up processes, and weakening of top-down ones, during the presentation of 'hollow' faces for the patients. In contrast, the controls exhibited a strengthening of top-down processes when perceiving the same stimuli. These findings suggest that schizophrenic patients rely on stimulus-driven processing and are less able to employ conceptually-driven top-down strategies during perception, where incoming sensory data are constrained with reference to a generative model that entails stored information from past experience.

Effective methylphenidate treatment of an adult Aspergers Syndrome and a comorbid ADHD: a clinical investigation with fMRI.

OBJECTIVE: Aspergers Syndrome can present as comorbid with attention-deficit/hyperactivity disorder (ADHD). Very few cases of the assessment and treatment of this comorbidity in adulthood are described in the research literature. METHOD: A 26-year-old patient as suffering from ADHD in combination with Aspergers Syndrome is diagnosed. Treatment is started with methylphenidate (MPH), and the patient's clinical response is observed, psychological tests concerning attention are analyzed, and a functional magnetic resonance imaging (fMRI) examination is performed during an attention-task. RESULTS: On the functional magnetic resonance imaging, a reduction of cerebral activity bilaterally in the parietal lobe under the influence of MPH is detected. CONCLUSION: Besides the neurophysiological findings, this case reports the complex impairment caused by the combination of AD/HD with Aspergers Syndrome and the broad social and behavioral benefits of treatment with MPH for this comorbidity.