Association of schizotypy with striatocortical functional connectivity and its asymmetry in healthy adults.

Altered striatocortical functional connectivity has been suggested to be a trait marker of schizophrenia spectrum disorders, including schizotypal personality. In the present study, we examined the association between schizotypal personality traits and striatocortical functional connectivity in a sample of healthy adults. The German version of the Schizotypal Personality Questionnaire was obtained from N = 111 participants recruited from the general public. Resting-state functional magnetic resonance imaging scans were acquired at 3T. Six striatal seed regions in each hemisphere were defined and striatocortical resting-state functional connectivity (rsFC) as well as its lateralization indices was calculated. Regression analysis showed that schizotypy scores, especially from the positive dimension, were positively correlated with rsFC between ventral striatum and frontal cortex and negatively associated with rsFC between dorsal striatum and posterior cingulate. No significant associations were found between negative dimension schizotypy and striatocortical rsFC. We also found positive correlations between schizotypy total scores and lateralization index of right dorsal caudate and right rostral putamen. In conclusion, the present study extends previous evidence of altered striatocortical rsFC in the schizophrenia spectrum. The observed associations resemble in part the alterations observed in psychotic patients and their relatives, providing support for dimensionality from schizotypal personality to the clinical disorder. Hum Brain Mapp 39:288-299, 2018. © 2017 Wiley Periodicals, Inc.

The effects of methylphenidate on whole brain intrinsic functional connectivity.

Methylphenidate (MPH) is an indirect dopaminergic and noradrenergic agonist that is used to treat attention deficit hyperactivity disorder and that has shown therapeutic potential in neuropsychiatric diseases such as depression, dementia, and Parkinson's disease. While effects of MPH on task-induced brain activation have been investigated, little is known about how MPH influences the resting brain. To investigate the effects of 40 mg of oral MPH on intrinsic functional connectivity, we used resting state fMRI in 54 healthy male subjects in a double-blind, randomized, placebo-controlled study. Functional connectivity analysis employing ICA revealed seven resting state networks (RSN) of interest. Connectivity strength between the dorsal attention network and the thalamus was increased after MPH intake. Other RSN located in association cortex areas, such as the left and right frontoparietal networks and the executive control network, showed MPH-induced connectivity increase to sensory-motor and visual cortex regions and connectivity decrease to cortical and subcortical components of cortico-striato-thalamo-cortical circuits (CST). RSN located in sensory-motor cortex areas showed the opposite pattern with MPH-induced connectivity increase to CST components and connectivity decrease to sensory-motor and visual cortex regions. Our results provide evidence that MPH does not only alter intrinsic connectivity between brain areas involved in sustained attention, but that it also induces significant changes in the cortico-cortical and cortico-subcortical connectivity of many other cognitive and sensory-motor RSN.

Task preparation and neural activation in stimulus-specific brain regions: an fMRI study with the cued task-switching paradigm.

To investigate the role of posterior brain regions related to task-relevant stimulus processing in task preparation, we used a cued task-switching paradigm in which a pre-cue informed participants about the upcoming task on a trial: face discrimination or number comparison. Employing an event-related fMRI design, we examined for changes of activity in face- and number-related posterior brain regions (right fusiform face area (FFA) and right intraparietal sulcus (IPSnum), respectively), and explored the functional connectivity of these areas with other brain regions, during the (preparation) interval between cue onset and onset of the (to-be-responded) target stimulus. The results revealed task-relevant posterior brain regions to be modulated during this period: activation in task-relevant stimulus-specific regions was selectively enhanced and their functional connectivity to task-relevant anterior brain regions strengthened (right FFA - face task, right IPSnum - number task) while participants prepared for the cued task. Additionally, activity in task-relevant posterior brain regions was influenced by residual activation from the preceding trial in the right FFA and the right IPSnum, respectively. These findings indicate that, during task preparation, the activation pattern in currently task-relevant posterior brain regions is shaped by residual activation as well as preparatory modulation prior to the onset of the critical stimulus, even without participants being instructed to imagine the stimulus.

Self processing in the brain: a paradigmatic fMRI case study with a professional singer.

Understanding the mechanisms involved in perception and conception of oneself is a fundamental psychological topic with high relevance for psychiatric and neurological issues, and it is one of the great challenges in neuroscientific research. The paradigmatic single-case study presented here aimed to investigate different components of self- and other-processes and to elucidate corresponding neurobiological underpinnings. An eminent professional opera singer with profound performance experience has undergone functional magnetic resonance imaging and was exposed to excerpts of Mozart arias, sung by herself or another singer. The results indicate a distinction between self- and other conditions in cortical midline structures, differentially involved in self-related and self-referential processing. This lends further support to the assumption of cortical midline structures being involved in the neural processing of self-specific stimuli and also confirms the power of single case studies as a research tool.

Methylphenidate effects on neural activity during response inhibition in healthy humans.

Methylphenidate (MPH) is a catecholamine transporter blocker, with dopamine agonistic effects in the basal ganglia. Response inhibition, error detection, and its mediating frontostriatal brain activation are improved by MPH in patients with attention-deficit/hyperactivity disorder. However, little is known about the effects of MPH on response inhibition and error processing or its underlying brain function in healthy individuals. Therefore, this study employed functional magnetic resonance imaging (fMRI) and 2 response inhibition tasks in 52 healthy males. Subjects underwent fMRI during a go/no-go task and a tracking stop-signal task after administration of 40 mg MPH and placebo in a double-blind, placebo-controlled, repeated-measures design. Results revealed task- and condition-specific neural effects of MPH: it increased activation in the putamen only during inhibition errors but not during successful inhibition and only in the go/no-go task. We speculate that task specificity of the effect might be due to differences in the degree of error saliency in the 2 task designs, whereas errors were few in the go/no-go task and thus had high saliency and the stop-signal task was designed to elicit 50% of errors in all subjects, diminishing the error saliency effect. The findings suggest that neural MPH effects interact with the saliency of the behavior under investigation.

The ε4 genotype of apolipoprotein E and white matter integrity in Alzheimer's disease.

BACKGROUND: In this multicenter study, we investigated a possible association between the APOE ε4 allele and white matter (WM) integrity in Alzheimer's disease (AD) using diffusion tensor imaging (DTI). METHODS: We analyzed fractional anisotropy (FA) and mean diffusivity (MD) as indices of WM integrity in 70 AD patients (35 APOE ε4 carriers, 35 noncarriers) and 56 healthy control (HC) subjects (28 APOE ε4 carriers, 28 noncarriers). APOE ε4 carriers and noncarriers were matched for age and gender within each diagnostic group. RESULTS: We found significant effects of diagnosis (Pcorrected < .05 [FWE]; i.e., smaller FA values and larger MD values in AD patients compared with HCs) and significant effects (P < .001) of APOE ε4 carrier status on MD in HCs but not in AD subjects. CONCLUSIONS: The results indicate that APOE ε4 has a moderate effect on WM integrity in HCs, but no effect on WM integrity in manifest AD.

Two Sides of the Same Coin in Female Borderline Personality Disorder: Self-Reported Guilt and Shame and Their Neurofunctional Correlates.

OBJECTIVE: Patients with borderline personality disorder (BPD) report to be especially prone to social emotions like shame and guilt. At the same time, these emotions seem to play an important role in BPD pathology. The present study aimed to deepen the knowledge about the processes behind shame and guilt in patients with BPD. METHODS: Twenty patients with BPD and twenty healthy controls (HCs) took part in an experiment that induced shame and guilt by imagining scenarios during scanning using functional brain imaging. Participants also filled out self-report questionnaires and took part in diagnostic interviews. RESULTS: BPD patients reported more proneness to guilt but not to shame than the HCs. There was no difference in the self-reported intensity rating of experimentally induced emotions between the groups. Between-group contrast of neural signals in the shame condition revealed a stronger activation of cingulate and fusiform gyrus for the BPD patients compared to the controls, and a more pronounced activation in the lingual gyrus and cuneus for the HCs. In the guilt condition, activation in the caudate nucleus, the fusiform gyrus, and the posterior cingulate cortex was stronger in BPD patients, while HC showed stronger activations in cuneus, lingual gyrus, and fronto-temporal regions. CONCLUSIONS: Differences in the neuro-functional processes between BPD patients and HC were found, even though the two groups did not differ in their self-report of subjective proneness to guilt and emotional intensity of shame and guilt during the experiment. While the HCs may be engaged more by the emotional scenarios themselves, the BPD patients may be more occupied with cognitive regulatory and self-referential processing.

Two Sides of Theory of Mind: Mental State Attribution to Moving Shapes in Paranoid Schizophrenia Is Independent of the Severity of Positive Symptoms.

BACKGROUND: Theory of Mind (ToM) impairment has repeatedly been found in paranoid schizophrenia. The current study aims at investigating whether this is related to a deficit in ToM (undermentalizing) or an increased ToM ability to hyperattribute others' mental states (overmentalizing). METHODS: Mental state attribution was examined in 24 patients diagnosed with schizophrenia (12 acute paranoid (APS) and 12 post-acute paranoid (PPS)) with regard to positive symptoms as well as matched healthy persons using a moving shapes paradigm. We used 3-T-functional magnetic resonance imaging (fMRI) to provide insights into the neural underpinnings of ToM due to attributional processes in different states of paranoid schizophrenia. RESULTS: In the condition that makes demands on theory of mind skills (ToM condition), in patients with diagnosed schizophrenia less appropriate mental state descriptions have been used, and they attributed mental states less often to the moving shapes than healthy persons. On a neural level, patients suffering from schizophrenia exhibited within the ToM network hypoactivity in the medial prefrontal cortex (MPFC) and hyperactivity in the temporo-parietal junction (TPJ) as compared to the healthy sample. CONCLUSIONS: Our results indicate both undermentalizing and hypoactivity in the MPFC and increased overattribution related to hyperactivity in the TPJ in paranoid schizophrenia, providing new implications for understanding ToM in paranoid schizophrenia.

Classifying fMRI-derived resting-state connectivity patterns according to their daily rhythmicity.

The vast majority of biological functions express rhythmic fluctuations across the 24-hour day. We investigated the degree of daily modulation across fMRI (functional Magnetic Resonance Imaging) derived resting-state data in 15 subjects by evaluating the time courses of 20 connectivity patterns over 8h (4 sessions). For each subject, we determined the chronotype, which describes the relationship between the individual circadian rhythm and the local time. We could therefore analyze the daily time course of the connectivity patterns controlling for internal time. Furthermore, as the participants' scan times were staggered as a function of their chronotype, we prevented sleep deprivation and kept time awake constant across subjects. Individual functional connectivity within each connectivity pattern was defined at each session as connectivity strength measured by a mean z-value and, in addition, as the spatial extent expressed by the number of activated voxels. Highly rhythmic connectivity patterns included two sub-systems of the Default-Mode Network (DMN) and a network extending over sensori-motor regions. The network characterized as the most stable across the day is mainly associated with processing of executive control. We conclude that the degree of daily modulation largely varies across fMRI derived resting-state connectivity patterns, ranging from highly rhythmic to stable. This finding should be considered when interpreting results from fMRI studies.

The Interplay of Oxytocin and Attachment in Schizophrenic Patients: An fMRI Study.

BACKGROUND: Attachment theory offers an important framework for understanding interpersonal interaction experiences. In the present study, we examined the neural correlates of attachment patterns and oxytocin in schizophrenic patients (SZP) compared to healthy controls (HC) using fMRI. We assumed that male SZP shows a higher proportion of insecure attachment and an altered level of oxytocin compared to HC. On a neural level, we hypothesized that SZP shows increased neural activation in memory and self-related brain regions during the activation of the attachment system compared to HC. METHODS: We used an event-related design for the fMRI study based on stimuli that were derived from the Adult Attachment Projective Picture System to examine attachment representations and their neural and hormonal correlates in 20 male schizophrenic patients compared to 20 male healthy controls. RESULTS: A higher proportion of insecure attachment in schizophrenic patients compared to HC could be confirmed. In line with our hypothesis, Oxytocin (OXT) levels in SZP were significantly lower than in HC. We found increasing brain activations in SZP when confronted with personal relevant sentences before attachment relevant pictures in the precuneus, TPJ, insula, and frontal areas compared to HC. Moreover, we found positive correlations between OXT and bilateral dlPFC, precuneus, and left ACC in SZP only. CONCLUSION: Despite the small sample sizes, the patients' response might be considered as a mode of dysregulation when confronted with this kind of personalized attachment-related material. In the patient group, we found positive correlations between OXT and three brain areas (bilateral dlPFC, precuneus, left ACC) and may conclude that OXT might modulate within this neural network in SZP.

Prefrontal transcranial direct current stimulation changes connectivity of resting-state networks during fMRI.

Transcranial direct current stimulation (tDCS) has been proposed for experimental and therapeutic modulation of regional brain function. Specifically, anodal tDCS of the dorsolateral prefrontal cortex (DLPFC) together with cathodal tDCS of the supraorbital region have been associated with improvement of cognition and mood, and have been suggested for the treatment of several neurological and psychiatric disorders. Although modeled mathematically, the distribution, direction, and extent of tDCS-mediated effects on brain physiology are not well understood. The current study investigates whether tDCS of the human prefrontal cortex modulates resting-state network (RSN) connectivity measured by functional magnetic resonance imaging (fMRI). Thirteen healthy subjects underwent real and sham tDCS in random order on separate days. tDCS was applied for 20 min at 2 mA with the anode positioned over the left DLPFC and the cathode over the right supraorbital region. Patterns of resting-state brain connectivity were assessed before and after tDCS with 3 T fMRI, and changes were analyzed for relevant networks related to the stimulation-electrode localizations. At baseline, four RSNs were detected, corresponding to the default mode network (DMN), the left and right frontal-parietal networks (FPNs) and the self-referential network. After real tDCS and compared with sham tDCS, significant changes of regional brain connectivity were found for the DMN and the FPNs both close to the primary stimulation site and in connected brain regions. These findings show that prefrontal tDCS modulates resting-state functional connectivity in distinct functional networks of the human brain.

The cholinergic system in mild cognitive impairment and Alzheimer's disease: an in vivo MRI and DTI study.

Few studies have investigated in vivo changes of the cholinergic basal forebrain in Alzheimer's disease (AD) and amnestic mild cognitive impairment (MCI), an at risk stage of AD. Even less is known about alterations of cortical projecting fiber tracts associated with basal forebrain atrophy. In this study, we determined regional atrophy within the basal forebrain in 21 patients with AD and 16 subjects with MCI compared to 20 healthy elderly subjects using deformation-based morphometry of MRI scans. We assessed effects of basal forebrain atrophy on fiber tracts derived from high-resolution diffusion tensor imaging (DTI) using tract-based spatial statistics. We localized significant effects relative to a map of cholinergic nuclei in MRI standard space as determined from a postmortem brain. Patients with AD and MCI subjects showed reduced volumes in basal forebrain areas corresponding to anterior medial and lateral, intermediate and posterior nuclei of the Nucleus basalis of Meynert (NbM) as well as in the diagonal band of Broca nuclei (P < 0.01). Effects in MCI subjects were spatially more restricted than in AD, but occurred at similar locations. The volume of the right antero-lateral NbM nucleus was correlated with intracortical projecting fiber tract integrity such as the corpus callosum, cingulate, and the superior longitudinal, inferior longitudinal, inferior fronto-occipital, and uncinate fasciculus (P < 0.05, corrected for multiple comparisons). Our findings suggest that a multimodal MRI-DTI approach is supportive to determine atrophy of cholinergic nuclei and its effect on intracortical projecting fiber tracts in AD.

Delineation of upper urinary tract segments at MDCT urography in patients with extra-urinary mass lesions: retrospective comparison of standard and low-dose protocols for the excretory phase of imaging.

PURPOSE: Excretory-phase CT urography (CTU) may replace excretory urography in patients without urinary tumors. However, radiation exposure is a concern. We retrospectively compared upper urinary tract (UUT) delineation in low-dose and standard CTU. MATERIAL AND METHODS: CTU (1-2 phases, 120 KV, 4 × 2.5 mm, pitch 0.875, i.v. non-ionic contrast media, iodine 36 g) was obtained with standard (14 patients, n = 27 UUTs, average 175.6 mAs/slice, average delay 16.8 min) or low-dose (26 patients, n = 86 UUTs, 29 mAs/slice, average delay 19.6 min) protocols. UUT was segmented into intrarenal collecting system (IRCS), upper, middle, and lower ureter (UU,MU,LU). Two independent readers (R1,R2) graded UUT segments as 1-not delineated, 2-partially delineated, 3-completely delineated (noisy margins), 4-completely delineated (clear margins). Chi-square statistics were calculated for partial versus complete delineation and complete delineation (clear margins), respectively. RESULTS: Complete delineation of UUT was similar in standard and low-dose CTU (R1, p > 0.15; R2, p > 0.2). IRCS, UU, and MU clearly delineated similarly often in standard and low-dose CTU (R1, p > 0.25; R2, p > 0.1). LU clearly delineated more often in standard protocols (R1, 18/6 standard, 38/31 low-dose, p > 0.1; R2 18/6 standard, 21/48 low-dose, p < 0.05). CONCLUSIONS: Low-dose CTU sufficiently delineated course of UUT and may locate obstruction/dilation, but appears unlikely to find intraluminal LU lesions.

Multicenter stability of diffusion tensor imaging measures: a European clinical and physical phantom study.

Diffusion tensor imaging (DTI) detects white matter damage in neuro-psychiatric disorders, but data on reliability of DTI measures across more than two scanners are still missing. In this study we assessed multicenter reproducibility of DTI acquisitions based on a physical phantom as well as brain scans across 16 scanners. In addition, we performed DTI scans in a group of 26 patients with clinically probable Alzheimer's disease (AD) and 12 healthy elderly controls at one single center. We determined the variability of fractional anisotropy (FA) measures using manually placed regions of interest as well as automated tract based spatial statistics and deformation based analysis. The coefficient of variation (CV) of FA was 6.9% for the physical phantom data. The mean CV across the multicenter brain scans was 14% for tract based statistics, and 29% for deformation based analysis. The degree of variation was higher in less organized fiber tracts. Our findings suggest that a clinical and physical phantom study involving more than two scanners is indispensable to detect potential sources of bias and to reliably estimate effect size in multicenter diagnostic trials using DTI.

Automated detection of brain atrophy patterns based on MRI for the prediction of Alzheimer's disease.

Subjects with mild cognitive impairment (MCI) have an increased risk to develop Alzheimer's disease (AD). Voxel-based MRI studies have demonstrated that widely distributed cortical and subcortical brain areas show atrophic changes in MCI, preceding the onset of AD-type dementia. Here we developed a novel data mining framework in combination with three different classifiers including support vector machine (SVM), Bayes statistics, and voting feature intervals (VFI) to derive a quantitative index of pattern matching for the prediction of the conversion from MCI to AD. MRI was collected in 32 AD patients, 24 MCI subjects and 18 healthy controls (HC). Nine out of 24 MCI subjects converted to AD after an average follow-up interval of 2.5 years. Using feature selection algorithms, brain regions showing the highest accuracy for the discrimination between AD and HC were identified, reaching a classification accuracy of up to 92%. The extracted AD clusters were used as a search region to extract those brain areas that are predictive of conversion to AD within MCI subjects. The most predictive brain areas included the anterior cingulate gyrus and orbitofrontal cortex. The best prediction accuracy, which was cross-validated via train-and-test, was 75% for the prediction of the conversion from MCI to AD. The present results suggest that novel multivariate methods of pattern matching reach a clinically relevant accuracy for the a priori prediction of the progression from MCI to AD.

Separating distinct aspects of the voluntary selection between response alternatives: N2- and P3-related BOLD responses.

Voluntary selection between response alternatives belongs to cognitive abilities controlling and regulating goal-directed behaviour. Voluntary selection processes are associated with increased neural activity, especially in medial and lateral frontal brain regions as well as the inferior parietal gyrus. However, the precise function of each brain region as well as the spatiotemporal characteristic of the brain regions involved is not yet clear. The aim of the present study was to disentangle distinct aspects of voluntary selection and their underlying neural processes. Hence, event-related potentials (ERPs) and functional MRI data were acquired simultaneously. Brain regions modulated by the task-induced amplitude variation of ERPs (N2, P3) were identified. The results showed N2-related hemodynamic responses, especially in medial and lateral frontal brain regions. Among other things, medial frontal brain regions are related to conflict monitoring, control of voluntary action and decision making. By contrast, the P3-amplitude proved to be predominantly related to increased BOLD responses in the temporo-parietal junction and lateral frontal brain regions. These brain regions are thought to play a decisive role in an attentional network involved in detecting auditory and visual stimuli. Overall, the results of the study indicated a whole network of brain regions to be associated with voluntary selection processes. In addition, at least some frontal brain regions seemed to be involved at an earlier stage than temporo-parietal regions, probably indicating a top-down process.

White matter microstructure underlying default mode network connectivity in the human brain.

Resting state functional magnetic resonance imaging (fMRI) reveals a distinct network of correlated brain function representing a default mode state of the human brain. The underlying structural basis of this functional connectivity pattern is still widely unexplored. We combined fractional anisotropy measures of fiber tract integrity derived from diffusion tensor imaging (DTI) and resting state fMRI data obtained at 3 Tesla from 20 healthy elderly subjects (56 to 83 years of age) to determine white matter microstructure underlying default mode connectivity. We hypothesized that the functional connectivity between the posterior cingulate and hippocampus from resting state fMRI data would be associated with the white matter microstructure in the cingulate bundle and fiber tracts connecting posterior cingulate gyrus with lateral temporal lobes, medial temporal lobes, and precuneus. This was demonstrated at the p<0.001 level using a voxel-based multivariate analysis of covariance (MANCOVA) approach. In addition, we used a data-driven technique of joint independent component analysis (ICA) that uncovers spatial pattern that are linked across modalities. It revealed a pattern of white matter tracts including cingulate bundle and associated fiber tracts resembling the findings from the hypothesis-driven analysis and was linked to the pattern of default mode network (DMN) connectivity in the resting state fMRI data. Our findings support the notion that the functional connectivity between the posterior cingulate and hippocampus and the functional connectivity across the entire DMN is based on distinct pattern of anatomical connectivity within the cerebral white matter.

Test-retest reproducibility of the default-mode network in healthy individuals.

Independent component analysis (ICA) of functional magnetic resonance imaging (fMRI) time-series reveals distinct coactivation patterns in the resting brain representing spatially coherent spontaneous fluctuations of the fMRI signal. Among these patterns, the so-called default-mode network (DMN) has been attributed to the ongoing mental activity of the brain during wakeful resting state. Studies suggest that many neuropsychiatric diseases disconnect brain areas belonging to the DMN. The potential use of the DMN as functional imaging marker for individuals at risk for these diseases, however, requires that the components of the DMN are reproducible over time in healthy individuals. In this study, we assessed the reproducibility of the DMN components within and between imaging sessions in 18 healthy young subjects (mean age, 27.5 years) who were scanned three times with two resting state scans during each session at 3.0 T field strength. Statistical analysis of fMRI time-series was done using ICA implemented with BrainVoyager QX. At all three sessions the essential components of the DMN could be identified in each individual. Spatial extent of DMN activity and size of overlap within and between sessions were most reproducible for the anterior and posterior cingulate gyrus. The degree of reproducibility of the DMN agrees with the degree of reproducibility found with motor paradigms. We conclude that DMN coactivation patterns are reproducible in healthy young subjects. Therefore, these data can serve as basis to further explore the effects of aging and neuropsychiatric diseases on the DMN of the brain.

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.

Neural correlates (ERP/fMRI) of voluntary selection in adult ADHD patients.

Deficits in executive functions, e.g. voluntary selection, are considered central to the attention-deficit/hyperactivity disorder (ADHD). The aim of this simultaneous EEG/fMRI study was to examine associated neural correlates in ADHD patients. Patients with ADHD and healthy subjects performed an adapted go/nogo task including a voluntary selection condition allowing participants to freely decide, whether to press the response button. Electrophysiologically, response inhibition and voluntary selection led to fronto-central responses. The fMRI data revealed increased medial/lateral frontal and parietal activity during the voluntary selection task. Frontal brain responses were reduced in ADHD patients compared to controls during free responses, whereas parietal brain functions seemed to be unaffected. These results may indicate that selection processes are related to dysfunctions, predominantly in frontal brain regions in ADHD patients.