Dorsolateral prefrontal cortex N-acetylaspartate/total creatine (NAA/tCr) loss in male recreational cannabis users.

BACKGROUND: Cannabinoids present neurotoxic and neuroprotective properties in in vitro studies, inconsistent alterations in human neuroimaging studies, neuropsychological deficits, and an increased risk for psychotic episodes. METHODS: Proton magnetic resonance spectroscopy ((1)H-MRS), neuropsychological testing, and hair analysis for cannabinoids was performed in 13 male nontreatment-seeking recreational cannabis users and 13 male control subjects. RESULTS: A significantly diminished N-acetylaspartate/total creatine (NAA/tCr) ratio in the dorsolateral prefrontal cortex (DLPFC) was observed in cannabis users (p = .0003). The NAA/tCr in the putamen/globus pallidum region correlated significantly with cannabidiol (R(2) = .66, p = .004). Results of the Wisconsin Card Sorting test, Trail making Test, and D2 test for attention were influenced by cannabinoids. CONCLUSIONS: Chronic recreational cannabis use is associated with an indication of diminished neuronal and axonal integrity in the DLPFC in this study. As chronic cannabis use is a risk factor for psychosis, these results are interesting because diminished NAA/tCr ratios in the DLPFC and neuropsychological deficits were also reported in schizophrenia. The strong positive correlation of NAA/tCr and cannabidiol in the putamen/globus pallidum is in line with neuroprotective properties of cannabidiol, which were also observed in in vitro model studies of Parkinson's disease.     

A multimodal approach using TMS and EEG reveals neurophysiological changes in Parkinson's disease

IntroductionAlterations in large scale neural networks leading to neurophysiological changes have been described in Parkinson's disease (PD). The combination of transcranial magnetic stimulation (TMS) and electroencephalography (EEG) has been suggested as a promising tool to identify and quantify neurophysiological mechanisms. The aim of this study was to investigate specific changes in electrical brain activity in response to stimulation of four brain areas in patients with PD.Methods21 healthy controls and 32 patients with PD underwent a combined TMS-EEG assessment that included stimulation of four brain areas: left M1, right M1, left dorso-lateral prefrontal cortex (DLPFC), and right DLPFC. Six measures were calculated to characterize the TMS evoked potentials (TEP) using EEG: (1) wave form adherence (WFA), (2) late phase deflection (LPD), (3) early phase deflection (EPD), (4) short-term plasticity (STP), (5) inter-trial adherence, and (6) connectivity between right and left M1 and DLPFC. A Linear mixed-model was used to compare these measures between groups and areas stimulated.ResultsPatients with PD showed lower WFA (p = 0.052), lower EPD (p = 0.009), lower inter-trial adherence (p < 0.001), and lower connectivity between homologs areas (p = 0.050), compared to healthy controls. LPD and STP measures were not different between the groups. In addition, lower inter-trial adherence correlated with longer disease duration (r = −0.355, p = 0.050).ConclusionsOur findings provide evidence to various alterations in neurophysiological measures in patients with PD. The higher cortical excitability along with increased variability and lower widespread of the evoked potentials in PD can elucidate different aspects related to the pathophysiology of the disease.     

Evidence for a Role of the Right Dorsolateral Prefrontal Cortex in Controlling Stimulus-response Integration: A Transcranial Direct Current Stimulation (tDCS) Study

BackgroundActing coherently upon stimuli requires some kind of integration of stimulus and response features across various distinct cortical feature maps (one aspect of the binding problem). Although the process of feature binding proper seems rather automatic, recent studies revealed that the management of stimulus-response bindings is less efficient in populations with impaired cognitive-control processes.ObjectiveHere, we investigated whether the cognitive control of stimulus-response feature bindings (“event files”) in healthy participants is affected by non-invasive brain stimulation (tDCS) of the dorsolateral prefrontal cortex (DLPFC)—a main component of the cognitive-control network.MethodIn different sessions, participants received anodal, cathodal, or sham tDCS (2 mA, 20 min) while performing an audio-visual event-file task assessing the creation and retrieval of stimulus–stimulus and stimulus-response feature bindings. The general findings from this task indicate that performance suffers when some, but not all of the features are repeated (the so-called partial repetition cost).ResultsStimulation over the right, but not the left DLPFC reduced control of stimulus-response bindings and produced outcome patterns similar to those previously observed in autistic children, people with lower fluid intelligence, and older adults.ConclusionsThis finding provides empirical support for a role of the right DLPFC in feature-binding management, which might consist in preventing the stimulus-induced activation of previously created, but now task-irrelevant, episodic bindings. From a methodological perspective, the finding may suggest that tDCS could be used as a temporary, reversible “brain lesion” generator in healthy subjects, enabling experimental investigation of how the brain works.     

Association analysis of the DISC1 gene with schizophrenia in the Japanese population and DISC1 immunoreactivity in the postmortem brain

The Disrupted-in-Schizophrenia 1 (DISC1) gene plays a role in the regulation of neural development. Previous evidence from genetic association and biological studies implicates the DISC1 gene as having a role in the pathophysiology of schizophrenia. In the present study, we explored the association between DISC1 missense mutation rs821616 (Ser704Cys) single nucleotide polymorphism (SNP) and four other SNPs (rs1772702, rs1754603, rs821621, rs821624) in the related haplotype block and schizophrenia in the Japanese population. We could not find a significant association of selected SNPs with schizophrenia after correction for multiple testing. We performed a meta-analysis of the Ser704Cys variant in schizophrenia using data from the present study and five previous Japanese population studies, and found no association with schizophrenia. We also examined DISC1 immunoreactivity in postmortem prefrontal cortex specimens of schizophrenia patients compared to control samples. The immunoreactivity revealed a significant decrease of DISC1 protein expression in the schizophrenia samples after ruling out potential confounding factors. However, the Ser704Cys variant did not show effects on DISC1 immunoreactivity. These results provide evidence that this functional genetic variation of DISC1 do not underlie the pathophysiology of schizophrenia in the Japanese population.     

Altered neural activation in ornithine transcarbamylase deficiency during executive cognition: An fMRI study

Background: Ornithine transcarbamylase deficiency (OTCD) is an X‐linked urea cycle disorder characterized by hyperammonemia resulting in white matter injury and impairments in working memory and executive cognition. Objective: To test for differences in BOLD signal activation between subjects with OTCD and healthy controls during a working memory task. Design, setting and patients: Nineteen subjects with OTCD and 21 healthy controls participated in a case‐control, IRB‐approved study at Georgetown University Medical Center. Intervention: An N‐back working memory task was performed in a block design using 3T functional magnetic resonance imaging. Results: In subjects with OTCD we observed increased BOLD signal in the right dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) relative to healthy age matched controls. Conclusions: Increased neuronal activation in OTCD subjects despite equivalent task performance points to sub‐optimal activation of the working memory network in these subjects, most likely reflecting damage caused by hyperammonemic events. These increases directly relate to our previous finding of reduced frontal white matter integrity in the superior extents of the corpus callosum; key hemispheric connections for these areas. Future studies using higher cognitive load are required to further characterize these effects. Hum Brain Mapp, 2013. © 2011 Wiley Periodicals, Inc.     

High-Frequency Transcranial Magnetic Stimulation Combined With Functional Magnetic Resonance Imaging Reveals Distinct Activation Patterns Associated With Different Dorsolateral Prefrontal Cortex Stimulation Sites

ObjectivesTranscranial magnetic stimulation (TMS) has been extensively used for the treatment of depression, obsessive-compulsive disorder, and certain neurologic disorders. Despite having promising treatment efficacy, the fundamental neural mechanisms of TMS remain understudied.Materials and MethodsIn this study, 15 healthy adult participants received simultaneous TMS and functional magnetic resonance imaging to map the modulatory effect of TMS when it was applied over three different sites in the dorsolateral prefrontal cortex. Independent component analysis (ICA) was used to identify the networks affected by TMS when applied over the different sites. The standard general linear model (GLM) analysis was used for comparison.ResultsICA showed that TMS affected the stimulation sites as well as remote brain areas, some areas/networks common across all TMS sites, and other areas/networks specific to each TMS site. In particular, TMS site and laterality differences were observed at the left executive control network. In addition, laterality differences also were observed at the dorsal anterior cingulate cortex and dorsolateral/dorsomedial prefrontal cortex. In contrast with the ICA findings, the GLM-based results mainly showed activation of auditory cortices regardless of the TMS sites.ConclusionsOur findings support the notion that TMS could act through a top-down mechanism, indirectly modulating deep subcortical nodes by directly stimulating cortical regions.Clinical Trial RegistrationThe Clinicaltrials.gov registration number for the study is NCT03394066.     

A lasting post-stimulus activation on dorsolateral prefrontal cortex is produced when processing valence and arousal in visual affective stimuli

This paper introduces a new paradigm in the study of emotional processes through functional neuroimaging. We study whether the valence and arousal of visual stimuli influence neuroimaging of the evoked hemodynamic changes. Using functional near-infrared spectroscopy (fNIRS), we investigate evoked-cerebral blood oxygenation (CBO) changes in dorsolateral prefrontal cortex (DLPFC) during direct exposure to different emotion-eliciting stimuli ('on' period), and during the period directly following stimulus cessation ('off' period). We hypothesize that the evoked-CBO, rather than return to baseline after stimulus cessation, would show either overshoot or undershoot. The study includes 30 healthy subjects and a total of 9 stimuli, which consist of video-clips with different emotional content. The total sample of trials studied (270) is classified according to the valence and arousal ratings given by the subjects. Results show a more robust activation in DLPFC during the 'off' period than during the 'on' period, depending on the subjective degree of arousal given to the stimulus. Our findings provide the first fNIRS evidence showing that an increment in subjective arousal leads to activation in DLPFC which persists after stimulus cessation and this does not occur with non-arousing stimuli. Neuroimaging studies must consider the duration and affective dimensions of the stimulus as well as the duration of the scanning to specify how much of the recorded response is analyzed. Not accounting for this difference may contribute to confusion in the data interpretation.     

Roman Catholic beliefs produce characteristic neural responses to moral dilemmas

This study provides exploratory evidence about how behavioral and neural responses to standard moral dilemmas are influenced by religious belief. Eleven Catholics and 13 Atheists (all female) judged 48 moral dilemmas. Differential neural activity between the two groups was found in precuneus and in prefrontal, frontal and temporal regions. Furthermore, a double dissociation showed that Catholics recruited different areas for deontological (precuneus; temporoparietal junction) and utilitarian moral judgments [dorsolateral prefrontal cortex (DLPFC); temporal poles], whereas Atheists did not (superior parietal gyrus for both types of judgment). Finally, we tested how both groups responded to personal and impersonal moral dilemmas: Catholics showed enhanced activity in DLPFC and posterior cingulate cortex during utilitarian moral judgments to impersonal moral dilemmas and enhanced responses in anterior cingulate cortex and superior temporal sulcus during deontological moral judgments to personal moral dilemmas. Our results indicate that moral judgment can be influenced by an acquired set of norms and conventions transmitted through religious indoctrination and practice. Catholic individuals may hold enhanced awareness of the incommensurability between two unequivocal doctrines of the Catholic belief set, triggered explicitly in a moral dilemma: help and care in all circumstances—but thou shalt not kill.     

Transcranial random noise stimulation is more effective than transcranial direct current stimulation for enhancing working memory in healthy individuals: Behavioural and electrophysiological evidence

BackgroundTranscranial direct current stimulation (tDCS) has been shown to improve working memory (WM) performance in healthy individuals, however effects tend to be modest and variable. Transcranial random noise stimulation (tRNS) can be delivered with a direct-current offset (DC-offset) to induce equal or even greater effects on cortical excitability than tDCS. To-date, no research has directly compared the effects of these techniques on WM performance or underlying neurophysiological activity.ObjectiveTo compare the effects of anodal tDCS, tRNS + DC-offset, or sham stimulation over the left dorsolateral prefrontal cortex (DLPFC) on WM performance and task-related EEG oscillatory activity in healthy adults.MethodsUsing a between-subjects design, 49 participants were allocated to receive either anodal tDCS (N = 16), high-frequency tRNS + DC-offset (N = 16), or sham stimulation (N = 17) to the left DLPFC. Changes in WM performance were assessed using the Sternberg WM task completed before and 5- and 25-min post-stimulation. Event-related synchronisation/desynchronisation (ERS/ERD) of oscillatory activity was analysed from EEG recorded during WM encoding and maintenance.ResultstRNS induced more pronounced and consistent enhancements in WM accuracy when compared to both tDCS and sham stimulation. Improvements in WM performance following tRNS were accompanied by increased theta ERS and diminished gamma ERD during WM encoding, which were significantly greater than those observed following anodal tDCS or sham stimulation.ConclusionsThese findings demonstrate the potential of tRNS + DC-offset to modulate cognitive and electrophysiological measures of WM and raise the possibility that tRNS + DC-offset may be more effective and reliable than tDCS for enhancing WM performance in healthy individuals.