A checklist for assessing the methodological quality of concurrent tES-fMRI studies (ContES checklist): a consensus study and statement.

Low-intensity transcranial electrical stimulation (tES), including alternating or direct current stimulation, applies weak electrical stimulation to modulate the activity of brain circuits. Integration of tES with concurrent functional MRI (fMRI) allows for the mapping of neural activity during neuromodulation, supporting causal studies of both brain function and tES effects. Methodological aspects of tES-fMRI studies underpin the results, and reporting them in appropriate detail is required for reproducibility and interpretability. Despite the growing number of published reports, there are no consensus-based checklists for disclosing methodological details of concurrent tES-fMRI studies. The objective of this work was to develop a consensus-based checklist of reporting standards for concurrent tES-fMRI studies to support methodological rigor, transparency and reproducibility (ContES checklist). A two-phase Delphi consensus process was conducted by a steering committee (SC) of 13 members and 49 expert panelists through the International Network of the tES-fMRI Consortium. The process began with a circulation of a preliminary checklist of essential items and additional recommendations, developed by the SC on the basis of a systematic review of 57 concurrent tES-fMRI studies. Contributors were then invited to suggest revisions or additions to the initial checklist. After the revision phase, contributors rated the importance of the 17 essential items and 42 additional recommendations in the final checklist. The state of methodological transparency within the 57 reviewed concurrent tES-fMRI studies was then assessed by using the checklist. Experts refined the checklist through the revision and rating phases, leading to a checklist with three categories of essential items and additional recommendations: (i) technological factors, (ii) safety and noise tests and (iii) methodological factors. The level of reporting of checklist items varied among the 57 concurrent tES-fMRI papers, ranging from 24% to 76%. On average, 53% of checklist items were reported in a given article. In conclusion, use of the ContES checklist is expected to enhance the methodological reporting quality of future concurrent tES-fMRI studies and increase methodological transparency and reproducibility.

Neural signature of error processing in major depression.

The clinical presentation of major depression (MD) is heterogenous and comprises various affective and cognitive symptoms including an increased sensitivity to errors. Various electrophysiological but only few functional magnetic resonance imaging (fMRI) studies investigated neural error processing in MD with inconsistent findings. Thus, reliable evidence regarding neural signatures of error processing in patients with current MD is limited despite its potential relevance as viable neurobiological marker of psychopathology. We therefore investigated a sample of 16 young adult female patients with current MD and 17 healthy controls (HC). During fMRI, we used an established Erikson-flanker Go/NoGo-paradigm and focused on neural alterations during errors of commission. In the absence of significant differences in rates of errors of commission in MD compared to HC, we observed significantly (p < 0.05, FWE-corrected on cluster level) enhanced neural activations of the dorsal anterior cingulate cortex (dACC) and the pre-supplementary motor area (pre-SMA) in MD relative to HC and thus, in brain regions consistently associated to neural error processing and corresponding behavioral adjustments. Considering comparable task performance, in particular similar commission error rates in MD and HC, our results support the evidence regarding an enhanced responsivity of neural error detection mechanisms in MD as a potential neural signature of increased negative feedback sensitivity as one of the core psychopathological features of this disorder.

Differential Neural Processing of Social Exclusion and Inclusion in Adolescents with Non-Suicidal Self-Injury and Young Adults with Borderline Personality Disorder.

INTRODUCTION: Non-suicidal self-injury (NSSI) is a symptom of borderline personality disorder (BPD). However, NSSI often occurs independently of BPD. Altered neural processing of social exclusion has been shown in adolescents with NSSI and adults with BPD with additional alterations during social inclusion in BPD patients. Aims of this study were to investigate differences in neural processing of social inclusion and exclusion situations between adolescents with NSSI and young adults with BPD and NSSI. METHODS: Using fMRI, neural processing of positive and negative social situations (paradigm: "Cyberball") was explored. Participants were 14 adolescents with NSSI, but without BPD (Mage = 15.4; SD = 1.9), 15 adults with BPD and NSSI (Mage = 23.3; SD = 4.1), as well as 15 healthy adolescents (Mage = 14.5; SD = 1.7), and 16 healthy adults (Mage = 23.2; SD = 4.4). RESULTS: Behavioral results showed enhanced feelings of social exclusion in both patient groups as compared to healthy controls but only the NSSI group showed enhanced activation during social exclusion versus inclusion compared to the other groups. While both NSSI and BPD groups showed enhanced activation in the ventral anterior cingulate cortex during social exclusion as compared to their age-matched controls, enhanced activation during social inclusion as compared to a passive watching condition was mainly observed in the BPD group in the dorsolateral and dorsomedial prefrontal cortex, and the anterior insula. DISCUSSION: While neural processing of social exclusion was pronounced in adolescents with NSSI, BPD patients also showed increased activity in a per se positive social situation. These results might point toward a higher responsiveness to social exclusion in adolescents with NSSI, which might then develop into a generalized increased sensitivity to all kinds of social situations in adults with BPD.

Differential neural processing of social exclusion in adolescents with non-suicidal self-injury: An fMRI study.

Non-suicidal self-injury (NSSI) is highly prevalent in adolescence and has been suggested as an autonomous diagnosis in the Diagnostic and Statistical Manual (DSM-5). Social rejection is as potential risk-factor for NSSI and depression in adolescence. Objectives of this study were to identify differences in neural processing of social rejection in depressed adolescents with and without co-morbid NSSI and healthy controls. Participants were 28 depressed adolescents (14 with co-morbid NSSI, 79% females) and 15 healthy controls, with an average age of 15.2 years (SD=1.8). Social exclusion was implemented using the Cyberball paradigm 'Cyberball' during functional magnetic resonance imaging (fMRI). All participants reported feelings of social exclusion after fMRI scanning. Investigating the effects of NSSI, we found that depressed adolescents with NSSI showed relatively enhanced activation of the medial prefrontal cortex (mPFC) and the ventrolateral prefrontal cortex (vlPFC) compared to depressed adolescents without NSSI and also compared to healthy controls. Results point towards divergent processing of social exclusion in depressed adolescents with NSSI as compared to adolescents with mere depression in brain regions previously related to the processing of social exclusion. This finding of distinct neurophysiological responses may stimulate further research on individual treatment approaches.

It's all about money: oral contraception alters neural reward processing.

Mating preferences in phases of the natural menstrual cycle with a low probability to conceive have been associated with lower interest in characteristics promising genetic benefits but increased search for safety and future security. We hypothesized that this effect would also be evident under oral contraception and may therefore alter neural processing of monetary rewards as a proxy for potential safety. Our aim was to assess the activation of reward-related brain areas using a monetary incentive task in women with functional MRI (fMRI). We compared fMRI activation of 12 young women taking oral contraceptives with 12 women with a natural hormonal cycle in their follicular phase during the expectation of monetary rewards. Women under hormonal contraception who have already shown decreased anterior insula activation upon erotic stimulation in a previous study of the same sample now showed enhanced activation during monetary reward expectation in the anterior insula/inferior lateral prefrontal cortex (t=2.84; P<0.05) relative to young normal cycling women in the follicular phase. Our finding supports the notion that the switch in mating preferences related to different hormonal states in women is mirrored by a switch in the stimulus-dependent excitability of reward-related brain regions. Beyond highlighting hormonal effects on reward processing, our data underline the importance of monitoring hormonal states in fMRI research in women.

Nonlinear correlations impair quantification of episodic memory by mesial temporal BOLD activity.

OBJECTIVE: Episodic memory processes can be investigated using different functional MRI (fMRI) paradigms. The purpose of the present study was to examine correlations between neuropsychological memory test scores and BOLD signal changes during fMRI scanning using three different memory tasks. METHOD: Twenty-eight right-handed healthy subjects underwent three paradigms, (a) a word pair, (b) a space-labyrinth, and (c) a face-name association paradigm. These paradigms were compared for their value in memory quantification and lateralization by calculating correlations between the BOLD signals in the mesial temporal lobe and behavioral data derived from a neuropsychological test battery. RESULTS: As expected, group analysis showed left-sided activation for the verbal, a tendency to right-sided activation for the spatial, and bilateral activation for the face-name paradigm. No linear correlations were observed between neuropsychological data and activation in the temporo-mesial region. However, we found significant u-shaped correlations between behavioral memory performance and activation in both the verbal and the face-name paradigms, that is, BOLD signal changes were greater not only among participants who performed best on the neuropsychological tests, but also among the poorest performers. The figural learning task did not correlate with the activations in the space-labyrinth paradigm at all. CONCLUSIONS: We interpreted the u-shaped correlations to be due to compensatory hippocampal activations associated with low performance when people try unsuccessfully to remember presented items. Because activation levels did not linearly increase with memory performance, the latter cannot be quantified by fMRI alone, but only be used in conjunction with neuropsychological testing.

Increased resting-state perfusion after repeated encoding is related to later retrieval of declarative associative memories.

Electrophysiological studies in animals have shown coordinated reactivation of neuronal ensembles during a restricted time period of behavioral inactivity that immediately followed active encoding. In the present study we directly investigated off-line processing of associative memory formation in the human brain. Subjects' regional cerebral blood flow (rCBF) as a surrogate marker of neural activity during rest was measured by MR-based perfusion imaging in a sample of 14 healthy male subjects prior to (Pre2) and after (Post) extensive learning of 24 face-name associations within a selective reminding task (SR). Results demonstrated significant Post-Pre2 rCBF increases in hippocampal and temporal lobe regions, while in a control comparison of two perfusion scans with no learning task in-between (Pre2-Pre1) no differences in rCBF emerged. Post perfusion scanning was followed by a surprise cued associative recall task from which two types of correctly retrieved names were obtained: older names already correctly retrieved at least once during one of the SR blocks, and recent names acquired during the last SR block immediately prior to the Post scan. In the anterior hippocampus individual perfusion increases were correlated with both correct retrievals of older and recent names. By contrast, older but not recently learned names showed a significant correlation with perfusion increases in the left lateral temporal cortex known to be associated with long-term memory. Recent, but not older names were correlated with dopaminergic midbrain structures reported to contribute to the persistence of memory traces for novel information. Although the direct investigation of off-line memory processing did not permit concomitant experimental control, neither intentional rehearsal, nor substantial variations in subjects' states of alertness appear to contribute to present results. We suggest that the observed rCBF increases might reflect processes that possibly contribute to the long-term persistence of memory traces.

Impulsiveness and ERP components in a Go/Nogo task.

Impulsiveness has been linked to fast guesses and premature responses in reaction time tasks like the Eriksen flanker task or the Go/Nogo task. In the present study, healthy subjects without history of DSM-IV Axis I or II psychopathology were examined. Impulsiveness was determined by calculating individual reaction times (as a function of general response speed) in order to split the entire group (n = 26) in a subgroup with a more controlled response style (low impulsiveness [LI] group; n = 13) and a subgroup with a more impulsive response style (high impulsiveness [HI] group; n = 13). Subjects performed a Go/Nogo task while a multi-channel EEG was recorded. Two event-related potentials (ERP) were of special interest: the Nogo-N2 and -P3 component. HI subjects had significantly reduced (less positive) Nogo-P3 amplitudes compared to LI subjects whereas groups did not differ with regard to the Nogo-N2. These results corroborate previous findings of reduced Nogo-P3 amplitudes in samples with enhanced levels of impulsiveness. Moreover, present data suggest that there is a broader range of impulsiveness even in healthy subjects which might mask or pronounce between-group differences in clinical studies. Therefore, different levels of impulsiveness in control groups should be carefully taken into account in further ERP studies.

Electrophysiological evidence for reduced inhibitory control in depressed patients in partial remission: a Go/Nogo study.

Major depressive disorder (MDD) can be characterized by a wide-ranging profile of cognitive deficits including attention, memory, and executive functions which is possibly due to reduced volumes and a hypometabolism of the anterior cingulate cortex, orbitofrontal, and dorsolateral prefrontal cortex. We examined 21 patients with MDD in partial remission and 21 age-, sex-, and education matched healthy controls using event-related potentials (ERPs). Participants performed a hybrid flanker Go/Nogo task while multichannel EEG was recorded. Two ERP components were of interest which repeatedly have been linked to response inhibition: the Nogo-N2 and the Nogo-P3 which can be observed in Nogo trials of a Go/Nogo task. MDD patients showed a specifically reduced Nogo-P3 while the Nogo-N2 and the P3b in Go trials were unaffected. These results provide further evidence of impaired response monitoring and control processes in patients with MDD.

Semantic and syntactic processes during sentence comprehension in patients with schizophrenia: evidence from event-related potentials.

Language and thought disorders are core symptoms in schizophrenia. We therefore studied language comprehension processes in patients with schizophrenia and control subjects during a sentence processing paradigm using event-related potentials (ERPs). In the ERP, assignment of syntactic structure to a string of words is reflected by an early left anterior negativity (ELAN) at about 80 ms after stimulus onset. Integration of syntactic and semantic information into a coherent representation is indexed by a positive potential at 600 ms (P600). Amplitudes of the ELAN and the P600 components are higher for grammatically incorrect sentences. Semantic processes are associated with a negative deflection peaking at 400 ms (N400). N400 amplitude is higher in semantically incongruent sentences. Nineteen patients with DSM IV schizophrenia and 19 healthy controls were presented with correct, semantically incorrect (semantic mismatch) and grammatically incorrect sentences (syntactic mismatch). Syntactic mismatch elicited an ELAN component in both subject groups. However, only controls but not patients with schizophrenia exhibited a P600 syntactic mismatch effect. Semantic mismatch was associated with a larger N400 potential which did not differ between groups. These results suggest that patients with schizophrenia are not impaired in syntactic structure assignment as reflected by the ELAN, but show deficits in semantic-syntactic integration processes underlying the P600.