Practical challenges of continuous real-time functional magnetic resonance imaging neurofeedback with multiband accelerated echo-planar imaging and short repetition times.

Continuous real-time functional magnetic resonance imaging (fMRI) neurofeedback is gaining increasing scientific attention in clinical neuroscience and may benefit from the short repetition times of modern multiband echoplanar imaging sequences. However, minimizing feedback delay can result in technical challenges. Here, we report a technical problem we experienced during continuous fMRI neurofeedback with multiband echoplanar imaging and short repetition times. We identify the possible origins of this problem, describe our current interim solution and provide openly available workflows and code to other researchers in case they wish to use a similar approach.

Structural alterations in brainstem, basal ganglia and thalamus associated with parkinsonism in schizophrenia spectrum disorders.

The relative roles of brainstem, thalamus and striatum in parkinsonism in schizophrenia spectrum disorder (SSD) patients are largely unknown. To determine whether topographical alterations of the brainstem, thalamus and striatum contribute to parkinsonism in SSD patients, we conducted structural magnetic resonance imaging (MRI) of SSD patients with (SSD-P, n = 35) and without (SSD-nonP, n = 64) parkinsonism, as defined by a Simpson and Angus Scale (SAS) total score of ≥ 4 and < 4, respectively, in comparison with healthy controls (n = 20). FreeSurfer v6.0 was used for segmentation of four brainstem regions (medulla oblongata, pons, superior cerebellar peduncle and midbrain), caudate nucleus, putamen and thalamus. Patients with parkinsonism had significantly smaller medulla oblongata (p = 0.01, false discovery rate (FDR)-corrected) and putamen (p = 0.02, FDR-corrected) volumes when compared to patients without parkinsonism. Across the entire patient sample (n = 99), significant negative correlations were identified between (a) medulla oblongata volumes and both SAS total (p = 0.034) and glabella-salivation (p = 0.007) scores, and (b) thalamic volumes and both SAS total (p = 0.033) and glabella-salivation (p = 0.007) scores. These results indicate that brainstem and thalamic structures as well as basal ganglia-based motor circuits play a crucial role in the pathogenesis of parkinsonism in SSD.

A Neural Signature of Parkinsonism in Patients With Schizophrenia Spectrum Disorders: A Multimodal MRI Study Using Parallel ICA.

Motor abnormalities in schizophrenia spectrum disorders (SSD) have increasingly attracted scientific interest in the past years. However, the neural mechanisms underlying parkinsonism in SSD are unclear. The present multimodal magnetic resonance imaging (MRI) study examined SSD patients with and without parkinsonism, as defined by a Simpson and Angus Scale (SAS) total score of ≥4 (SAS group, n = 22) or <4 (non-SAS group, n = 22). Parallel independent component analysis (p-ICA) was used to examine the covarying components among gray matter volume maps computed from structural MRI (sMRI) and fractional amplitude of low-frequency fluctuations (fALFF) maps computed from resting-state functional MRI (rs-fMRI) patient data. We found a significant correlation (P = .020, false discovery rate [FDR] corrected) between an sMRI component and an rs-fMRI component, which also significantly differed between the SAS and non-SAS group (P = .042, z = -2.04). The rs-fMRI component comprised the cortical sensorimotor network, and the sMRI component included predominantly a frontothalamic/cerebellar network. Across the patient sample, correlations adjusted for the Positive and Negative Syndrome Scale (PANSS) total scores showed a significant relationship between tremor score and loadings of the cortical sensorimotor network, as well as between glabella-salivation score, frontothalamic/cerebellar and cortical sensorimotor network loadings. These data provide novel insights into neural mechanisms of parkinsonism in SSD. Aberrant bottom-up modulation of cortical motor regions may account for these specific motor symptoms, at least in patients with SSD.

Ketamine Suppresses the Ventral Striatal Response to Reward Anticipation: A Cross-Species Translational Neuroimaging Study.

Convergent evidence implicates regional neural responses to reward anticipation in the pathogenesis of several psychiatric disorders, such as schizophrenia, where blunted ventral striatal responses to positive reward are observed in patients and at-risk populations. In vivo oxygen amperometry measurements in the ventral striatum in awake, behaving rats reveal reward-related tissue oxygen changes that closely parallel blood oxygen level dependent (BOLD) signal changes observed in human functional magnetic resonance imaging (fMRI), suggesting that a cross-species approach targeting this mechanism might be feasible in psychopharmacology. The present study explored modulatory effects of acute, subanaesthetic doses of ketamine-a pharmacological model widely used in psychopharmacological research, both preclinically and clinically-on ventral striatum activity during performance of a reward anticipation task in both species, using fMRI in humans and in vivo oxygen amperometry in rats. In a region-of-interest analysis conducted following a cross-over placebo and ketamine study in human subjects, an attenuated ventral striatal response during reward anticipation was observed following ketamine relative to placebo during performance of a monetary incentive delay task. In rats, a comparable attenuation of ventral striatal signal was found after ketamine challenge, relative to vehicle, in response to a conditioned stimulus that predicted delivery of reward. This study provides the first data in both species demonstrating an attenuating effect of acute ketamine on reward-related ventral striatal (O2) and fMRI signals. These findings may help elucidate a deeper mechanistic understanding of the potential role of ketamine as a model for psychosis, show that cross-species pharmacological experiments targeting reward signaling are feasible, and suggest this phenotype as a promising translational biomarker for the development of novel compounds, assessment of disease status, and treatment efficacy.

A common allele in the oxytocin receptor gene (OXTR) impacts prosocial temperament and human hypothalamic-limbic structure and function.

The evolutionarily highly conserved neuropeptide oxytocin is a key mediator of social and emotional behavior in mammals, including humans. A common variant (rs53576) in the oxytocin receptor gene (OXTR) has been implicated in social-behavioral phenotypes, such as maternal sensitivity and empathy, and with neuropsychiatric disorders associated with social impairment, but the intermediate neural mechanisms are unknown. Here, we used multimodal neuroimaging in a large sample of healthy human subjects to identify structural and functional alterations in OXTR risk allele carriers and their link to temperament. Activation and interregional coupling of the amygdala during the processing of emotionally salient social cues was significantly affected by genotype. In addition, evidence for structural alterations in key oxytocinergic regions emerged, particularly in the hypothalamus. These neural characteristics predicted lower levels of reward dependence, specifically in male risk allele carriers. Our findings identify sex-dependent mechanisms impacting the structure and function of hypothalamic-limbic circuits that are of potential clinical and translational significance.

Pedophilia: neuropsychological evidence encouraging a brain network perspective.

Although the vast majority of current pathogenetic theories support a neurobiological understanding of psychiatric disorders, the brain functional correlates of pedophilia are largely unknown. Based on prior behavior genetics research on human sexual orientation and phenomenology as well as the phenotypical intersection of pedophilia with other psychiatric spectrum disorders, we hypothesize the involvement of striato-thalamo-cortical processing loops in the formation of pedophilic urges and behaviors. Data from a current neuropsychological pilot study in four pedophiles encourage our brain functional perspective. As deduced from the network model, all four patients exhibited pronounced and circumscribed deficits in cognitive domains mediated by striato-thalamically controlled areas of the frontal cortex. All patients were especially impaired in neuropsychological functions associated with the prefrontal and motor processing loops (e.g., response inhibition, working memory and cognitive flexibility), with a performance level located up to five standard deviations below the normative data. Contrary to this, neuropsychological performances in cognitive domains without a comparable high frontal loading were in all participants unobtrusive. In future, studying gene by environment interactions in combination with functional neuroimaging and neuropsychological assessment is promising to elucidate the pathophysiological relationship of psychiatric disorders that are characterized by inadequate urges and poor behavioral inhibition.

Haloperidol challenge in healthy male humans: a functional magnetic resonance imaging study.

Functional magnetic resonance imaging (fMRI) was used to determine the acute blood oxygen level dependent effect (BOLD) of neuroleptic drugs in healthy male subjects. Using a robust simultaneous visuo-acoustic stimulation paradigm fMRI measurements were obtained prior to as well as 1 h and 24 h after intravenous infusion of 5 mg haloperidol to six healthy young men. After the administration, subjects showed significantly reduced BOLD contrast in the middle occipital gyrus while BOLD contrast was increased in the lingual gyrus. This pattern normalised within 24 h. Our results emphasise the necessity to control for interactions through acute medication and confirm fMRI as a non-invasive method for studying cerebral psychopharmacological effects.

Sensory information processing in neuroleptic-naive first-episode schizophrenic patients: a functional magnetic resonance imaging study.

BACKGROUND: Schizophrenic disorders are thought to involve widespread abnormalities in information processing. The present study used functional magnetic resonance imaging and a simple and robust paradigm that involved auditory and visual activation to examine basic sensory input circuits. Our aim was to determine which stages of the input processing network are disturbed in first-episode schizophrenic patients. METHODS: Twelve neuroleptic-naive inpatients (paranoid subtype) were compared with 11 healthy subjects by means of echo-planar functional magnetic resonance imaging. In a block design, the paradigm included the simultaneous presentation of a moving 6-Hz checkerboard and auditory stimuli in the form of drumbeats. The subjects were asked to simply look and listen. RESULTS: In comparison with control subjects, patients showed reduced activation in the right thalamus, the right prefrontal cortex, and the parietal lobe (restricted to the dorsal visual pathway) bilaterally. There were no notable differences in the primary visual cortex or the object-specific occipitotemporal pathway. In addition, patients presented with a reduced signal change to auditory stimulation in the left acoustic cortex. CONCLUSIONS: The present study supports the concept of widespread cortical and subcortical deficits in schizophrenia. Our findings suggest abnormal functioning early in the information processing and in high-order association cortices already at illness onset, before the administration of medication or the most confounding effects of illness duration. The main regions have been implicated in visual motion perception and discrimination as well as in attention to sensorial events and perceptual synthesis.