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Contains fulltext : 299351.pdf (Publisher’s version ) (Open Access), Introduction (Background): Depression is an often chronic condition, characterized by wide-ranging physical, cognitive and psychosocial symptoms that can lead to disability, premature mortality or suicide. It affects 350 million people globally, yet up to 30% do not respond to traditional treatment, creating an urgent need for novel non-pharmacological treatments. This open-label naturalistic study assesses the practical feasibility, tolerability, and clinical effectiveness of home-administered transcranial direct current stimulation (tDCS) with asynchronous remote supervision, in the treatment of depression. Method: Over the course of 3 weeks, 40 patients with depression received psychotherapy and half of this group also received daily bi-frontal tDCS stimulation of the dorsolateral prefrontal cortex. These patients received tDCS for 30 min per session with the anode placed over F3 and the cathode over F4, at an intensity of 2 mA for 21 consecutive days. We measured patients' level of depression symptoms at four time points using the Beck Depression Inventory, before treatment and at 1-week intervals throughout the treatment period. We monitored practical feasibility such as daily protocol compliance and tolerability including side effects, with the PlatoScience cloud-based remote supervision platform. Results: Of the 20 patients in the tDCS group, 90% were able to comply with the protocol by not missing more than three of their assigned sessions, and none dropped out of the study. No serious adverse events were reported, with only 14 instances of mild to moderate side effects and two instances of scalp pain rated as severe, out of a total of 420 stimulation sessions. Patients in the tDCS group showed a significantly greater reduction in depression symptoms after 3 weeks of treatment, compared to the treatment as usual (TAU) group [t(57.2) = 2.268, p = 0.027]. The tDCS group also showed greater treatment response (50%) and depression remission rates (75%) compared, 11 p.

Item does not contain fulltext, This study aimed at examining cognitive predictors of reactive and proactive aggression in a forensic-psychiatric (n = 80) and a non-clinical sample (n = 98; Brugman et al., 2015). Three different cognitive predictors were incorporated: (1) attentional bias towards aggressive stimuli (measured with Emotional Stroop task) and towards angry faces (measured with a visual search task); (2) interpretation biases (measured with Aggressive Interpretative Bias Task (AIBT) and a vignette task), and (3) implicit self-aggression association (measured with a Single-Target Implicit Association Task). To measure aggression, the Reactive-Proactive Aggression Questionnaire (RPQ) and the Taylor Aggression Paradigm (TAP) were used. An automatic self-aggression association positively predicted proactive aggressive behavior on the TAP in both samples. Furthermore, this self-aggression association predicted, increased self-reported proactive aggression (RPQ) in the forensic sample only. Pain, injury, and danger interpretations reported on the vignettes, negatively predicted self-reported proactive aggression in both samples. A stronger aggressive interpretation bias on the AIBT predicted more reactive aggressive behavior (TAP) in the non-clinical sample only. Taken together, findings show both common and distinct mechanisms in reactively vs. proactively driven aggressive behavior.

The noninvasive methods of cognitive neuroscience offer new possibilities to study language. We used neuronavigated multisite transcranial magnetic stimulation (TMS) to determine the functional relevance of 1) the posterior part of left superior temporal gyrus (Wernicke's area), 2) a midportion of Broca's area (slightly posterior/superior to apex of vertical ascending ramus), and 3) the midsection of the left middle temporal gyrus (MTG), during overt picture naming. Our chronometric TMS design enabled us to chart the time points at which neural activity in each of these regions functionally contributes to overt speech production. Our findings demonstrate that the midsection of left MTG becomes functionally relevant at 225 ms after picture onset, followed by Broca's area at 300 ms and Wernicke's area at 400 ms. Interestingly, during this late time window, the left MTG shows a second peak of functional relevance. Each area thus contributed during the speech production process at different stages, suggesting distinct underlying functional roles within this complex multicomponential skill. These findings are discussed and framed in the context of psycholinguistic models of speech production according to which successful speaking relies on intact, spatiotemporally specific feed forward and recurrent feedback loops within a left-hemispheric fronto-temporal brain connectivity network.

The opercular and triangular sections of the inferior frontal gyrus, also known as Broca's area, have been shown to be involved in various language tasks. In the current study we investigated both the functional role, as well as the precise temporal involvement of Broca's area during picture naming. We applied online event-related transcranial magnetic stimulation (TMS) to Broca's area at five different time points after picture presentation, aiming to cover the complete language production process. Applying real TMS at 300 msec after picture presentation led to an increase in picture naming latency, whereas sham stimulation and real stimulation at earlier and later time windows did not result in any changes in reaction time (RT). Our methodological approach enabled us to get insight into the temporal characteristics of the involvement of this brain area during picture naming. Making use of this information and directly relating it to psycholinguistic models, we conclude that Broca's area may be involved in the process of syllabification during overt speech production.

Item does not contain fulltext, This study tested the predictive value of attentional bias, emotion recognition, automatic associations, and response inhibition, in the assessment of in-clinic violent incidents. Sixty-nine male forensic patients participated and completed an Emotional Stroop to measure attentional bias for threat and aggression, a Single Target - Implicit Association Task to assess automatic associations, a Graded Emotional Recognition Task to measure emotion recognition, and an Affective Go/NoGo to measure response inhibition. Violent incidents were derived from patient files and scored on severity level. The predictive value of level of psychopathy was tested with the Psychopathy Checklist - Revised (PCL-R). Generalized linear mixed model analyses showed that increased attention towards threat and aggression, difficulty recognizing sad faces and factor 2 of the PCL-R predicted the sum of violent incidents. Specifically, verbal aggression was predicted by increased attention towards threat and aggression, difficulty to recognize sad and happy faces, and PCL-R factor 2; physical aggression by decreased response inhibition, higher PCL-R factor 2 and lower PCL-R factor 1 scores; and aggression against property by difficulty recognizing angry faces. Findings indicate that cognitive tasks could be valuable in predicting aggression, thereby extending current knowledge on dynamic factors predicting aggressive behavior in forensic patients.

Recent evidence has revealed an advantage for movements to last target positions in a structured visual display, suggesting a mediating role of allocentric, in addition to egocentric, information in goal-directed reaching. This notion is accommodated by the recently updated perception-action model (Milner and Goodale, 2008), which postulates functional roles of ventral and dorsal neural areas in allocentric coding. In the present study, we used imaging-guided multi-site continuous theta burst stimulation (cTBS) over regions of the ventral and dorsal processing streams to unravel their functional contribution on visually guided reaching in two display conditions: the "egocentric" condition where the target appeared in an empty display and the "allocentric" condition where the target appeared in a structured display with placeholders marking possible target locations. Cortical sites for cTBS were identified individually for each participant via coregistration with magnetic resonance scans. Results indicated that cTBS in the egocentric condition did not affect movement time, but cTBS in the allocentric condition modulated movement time contingent on stimulation site and target position. In particular, cTBS over the lateral occipital cortex (part of the ventral stream) and over the angular gyrus (part of the dorsal stream) eliminated the last-target advantage by slowing down reaching to the salient last target position. cTBS over the superior parietal occipital cortex did not affect the last-target advantage. These outcomes provide the first causal evidence for allocentric coding in ventral and dorsal routes during real-time reaching, thereby supporting the updated perception-action model. (C) 2015 Elsevier B.V. All rights reserved.

The aim of this study was to identify implicit cognitive predictors of aggressive behavior. Specifically, the predictive value of an attentional bias for aggressive stimuli and automatic association of the self and aggression was examined for reactive and proactive aggressive behavior in a non-clinical sample (N = 90). An Emotional Stroop Task was used to measure an attentional bias. With an idiographic Single-Target Implicit Association Test, automatic associations were assessed between words referring to the self (e.g., the participants' name) and words referring to aggression (e.g., fighting). The Taylor Aggression Paradigm (TAP) was used to measure reactive and proactive aggressive behavior. Furthermore, self-reported aggressiveness was assessed with the Reactive Proactive Aggression Questionnaire (RPQ). Results showed that heightened attentional interference for aggressive words significantly predicted more reactive aggression, while lower attentional bias towards aggressive words predicted higher levels of proactive aggression. A stronger self-aggression association resulted in more proactive aggression, but not reactive aggression. Self-reports on aggression did not additionally predict behavioral aggression. This implies that the cognitive tests employed in our study have the potential to discriminate between reactive and proactive aggression. Aggr. Behav. 9999:XX-XX, 2014. (c) 2014 Wiley Periodicals, Inc.

Aggressive behavior poses a threat to human collaboration and social safety. It is of utmost importance to identify the functional mechanisms underlying aggression and to develop potential interventions capable of reducing dysfunctional aggressive behavior already at a brain level. We here experimentally shifted fronto-cortical asymmetry to manipulate the underlying motivational emotional states in both male and female participants while assessing the behavioral effects on proactive and reactive aggression. Thirty-two healthy volunteers received either anodal transcranial direct current stimulation to increase neural activity within right dorsolateral prefrontal cortex, or sham stimulation. Aggressive behavior was measured with the Taylor Aggression Paradigm (TAP). We revealed a general gender effect, showing that males displayed more behavioral aggression than females. After the induction of right fronto-hemispheric dominance, proactive aggression was reduced in males. The current study demonstrates that non-invasive brain stimulation can reduce aggression in males. This is a relevant and promising step to better understand how cortical brain states connect to impulsive actions and to examine the causal role of the prefrontal cortex in aggression. Ultimately such findings could help to examine whether the brain can be a direct target for potential supportive interventions in clinical settings dealing with overly aggressive patients and/or violent offenders.

Social norms, such as treating others fairly regardless of kin relations, are essential for the functioning of human societies. Their existence may explain why humans, among all species, show unique patterns of pro-social behaviour (Sethi and Somanathan, 1996; Gintis, 2000; Ostrom, 2000; Fehr and Fischbacher, 2003; Gintis, 2003). The maintenance of social norms often depends on external enforcement, as in the absence of credible sanctioning mechanisms pro-social behaviour deteriorates quickly (Fehr and Gachter, 2000; Fehr and Fischbacher, 2004). This sanction-dependent pro-social behaviour suggests that humans strategically adapt their behaviour and act selfishly if possible but control selfish impulses if necessary. Recent studies point at the role of the dorsolateral prefrontal cortex (DLPFC) in controlling selfish impulses (Wout et al., 2005; Knoch et al., 2006; Knoch et al., 2009; Ruff et al., 2013). We test, whether the DLPFC is indeed involved in the control of selfish impulses as well as the strategic acquisition of this control mechanism. Using repetitive transcranial magnetic stimulation, we provide evidence for the causal role of the right DLPFC in strategic fairness. Since the DLPFC is phylogenetically one of the latest developed neocortical regions (Fuster, 2001) this could explain why complex norm systems exist in humans but not in other social animals. data source: lab experiment data, available from authors upon request

The ability to inhibit action tendencies is vital for adaptive human behaviour. Various paradigms are supposed to assess action inhibition and are often used interchangeably. However, these paradigms are based on different conceptualizations (action restraint vs. action cancellation) and the question arises as to what extent different conceptualizations of inhibitory processing are mirrored in a distinct neural activation pattern. We used functional magnetic resonance imaging to investigate the neural correlates of action restraint vs. action cancellation. Analyses of local activity changes as well as network connectivity measures revealed a strong overlap of activation within a common action inhibition network including inferior frontal, pre-supplementary motor and thalamic brain areas as well as the anterior cingulate cortex. Furthermore, our findings pointed to additional neural networks that are distinct for action restraint (i.e. right superior frontal gyrus, left middle frontal gyrus, and bilateral anterior cingulate cortex) and action cancellation (i.e. right middle frontal gyrus, posterior cingulate cortex, and parietal regions). Our connectivity analyses showed that different inhibitory modalities largely relied on a task-independent global inhibition network within the brain. Furthermore, they suggested that the conceptually distinct inhibitory aspects of action restraint vs. action cancellation also activated additional specific brain regions in a task-dependent manner. This has implications for the choice of tasks in an empirical setting, but is also relevant for various clinical contexts in which inhibition deficits are considered a diagnostic feature.

The ability of inhibiting impulsive urges is paramount for human behavior. Such successful response inhibition has consistently been associated with activity in pFC. The current study aims to unravel the differential involvement of different areas within right pFC for successful action restraint versus action cancellation. These two conceptually different aspects of action inhibition were measured with a go/no-go task (action restraint) and a stop signal task (action cancellation). Localization of relevant prefrontal activation was based on fMRI data. Significant task-related activation during successful action restraint was localized for each participant individually in right anterior insula (rAI), right superior frontal gyrus, and pre-SMA. Activation during successful action cancellation was localized in rAI, right middle frontal gyrus, and pre-SMA. Subsequently, fMRI-guided continuous thetaburst stimulation was applied to these regions. Results showed that the disruption of neural activity in rAI reduced both the ability to restrain (go/no-go) and cancel (stop signal) responses. In contrast, continuous thetaburst stimulation-induced disruption of the right superior frontal gyrus specifically impaired the ability to restrain from responding (go/no-go), while leaving the ability for action cancellation largely intact. Stimulation applied to right middle frontal gyrus and pre-SMA did not affect inhibitory processing in neither of the two tasks. These findings provide a more comprehensive perspective on the role of pFC in inhibition and cognitive control. The results emphasize the role of inferior frontal regions for global inhibition, whereas superior frontal regions seem to be specifically relevant for successful action restraint.

Peters JC, Reithler J, Schuhmann T, de Graaf T, Uludag. K, Goebel R, Sack AT. On the feasibility of concurrent human TMS-EEG-fMRI measurements. J Neurophysiol 109: 1214-1227, 2013. First published December 5, 2012; doi:10.1152/jn.00071.2012.-Simultaneously combining the complementary assets of EEG, functional MRI (fMRI), and transcranial magnetic stimulation (TMS) within one experimental session provides synergetic results, offering insights into brain function that go beyond the scope of each method when used in isolation. The steady increase of concurrent EEG-fMRI, TMS-EEG, and TMS-fMRI studies further underlines the added value of such multimodal imaging approaches. Whereas concurrent EEG-fMRI enables monitoring of brain-wide network dynamics with high temporal and spatial resolution, the combination with TMS provides insights in causal interactions within these networks. Thus the simultaneous use of all three methods would allow studying fast, spatially accurate, and distributed causal interactions in the perturbed system and its functional relevance for intact behavior. Concurrent EEG-fMRI, TMS-EEG, and TMS-fMRI experiments are already technically challenging, and the three-way combination of TMS-EEG-fMRI might yield additional difficulties in terms of hardware strain or signal quality. The present study explored the feasibility of concurrent TMS-EEG-fMRI studies by performing safety and quality assurance tests based on phantom and human data combining existing commercially available hardware. Results revealed that combined TMS-EEG-fMRI measurements were technically feasible, safe in terms of induced temperature changes, allowed functional MRI acquisition with comparable image quality as during concurrent EEG-fMRI or TMS-fMRI, and provided artifact-free EEG before and from 300 ms after TMS pulse application. Based on these empirical findings, we discuss the conceptual benefits of this novel complementary approach to investigate the working human brain and list

Magnetoencephalography (MEG) has shown pseudohomophone priming effects at Broca's area (specifically pars opercularis of left inferior frontal gyrus and precentral gyrus; LIFGpo/PCG) within approximately 100ms of viewing a word. This is consistent with Broca's area involvement in fast phonological access during visual word recognition. Here we used online transcranial magnetic stimulation (TMS) to investigate whether LIFGpo/PCG is necessary for (not just correlated with) visual word recognition by approximately 100ms. Pulses were delivered to individually fMRI-defined LIFGpo/PCG in Dutch speakers 75-500ms after stimulus onset during reading and picture naming. Reading and picture naming reactions times were significantly slower following pulses at 225-300ms. Contrary to predictions, there was no disruption to reading for pulses before 225ms. This does not provide evidence in favour of a functional role for LIFGpo/PCG in reading before 225ms in this case, but does extend previous findings in picture stimuli to written Dutch words.

Recent psychophysics studies suggest that the behavioral impact of a visual stimulus and its conscious visual recognition underlie two functionally dissociated neuronal processes. Previous TMS studies have demonstrated that certain features of a visual stimulus can still be processed despite TMS-induced disruption of perception. Here, we tested whether symbolic action priming also remains intact despite TMS-induced masking of the prime. We applied single-pulse TMS over primary visual cortex at various temporal intervals from 20 ms to 120 ms during a supraliminal action priming paradigm. This TMS protocol enabled us to identify at what exact time point a TMS-induced activity disruption of primary visual cortex interferes with conscious visual perception of the prime versus (un)conscious behavioral priming of the visual target stimulus. We also introduced spatial uncertainty by presenting visual stimuli either above or below the fixation cross, while the TMS pulse was always targeting the prime presented below fixation. We revealed that TMS over primary visual cortex interferes with both conscious visual perception and symbolic behavioral priming in a temporarily and spatially specific manner, i.e., only when disrupting primary visual cortex at approximately the same temporal stage between 60 and 100 ms after prime onset, and only for those prime stimuli presented below fixation. These findings are in disagreement with the idea of subliminal action priming being mediated by neural pathways bypassing striate cortex, and rather suggest that symbolic action priming relies on an intact neural transmission along the retino-geniculo-striate pathway. The implications of our findings for previous reports of residual visual processing during striate TMS are discussed.

Transcranial magnetic stimulation (TMS) is a tool for inducing transient disruptions of neural activity noninvasively in conscious human volunteers. In recent years, the investigative domain of TMS has expanded and now encompasses causal structure-function relationships across the whole gamut of cognitive functions and associated cortical brain regions. Consequently, the importance of how to determine the target stimulation site has increased and a number of alternative methods have emerged. Comparison across studies is precluded because different studies necessarily use different tasks, sites, TMS conditions, and have different goals. Here, therefore, we systematically compare four commonly used TMS coil positioning approaches by using them to induce behavioral change in a single cognitive study. Specifically, we investigated the behavioral impact of right parietal TMS during a number comparison task, while basing TMS localization either on (i) individual fMRI-guided TMS neuronavigation, (ii) individual MRI-guided TMS neuronavigation, (iii) group functional Talairach coordinates, or (iv) 10-20 EEG position P4. We quantified the exact behavioral effects induced by TMS using each approach, calculated the standardized experimental effect sizes, and conducted a statistical power analysis in order to calculate the optimal sample size required to reveal statistical significance. Our findings revealed a systematic difference between the four approaches, with the individual fMRI-guided TMS neuronavigation yielding the strongest and the P4 stimulation approach yielding the smallest behavioral effect size. Accordingly, power analyses revealed that although in the fMRI-guided neuronavigation approach five participants were sufficient to reveal a significant behavioral effect, the number of necessary participants increased to n = 9 when employing MRI-guided neuronavigation, to n = 13 in case of TMS based on group Talairach coordinates, and to n = 47 when applying TMS over P4.

People suffering from developmental dyscalculia encounter difficulties in automatically accessing numerical magnitudes [1-3]. For example, when instructed to attend to the physical size of a number while ignoring its numerical value, dyscalculic subjects, unlike healthy participants, fail to process the irrelevant dimension automatically and subsequently show a smaller size-congruity effect (difference in reaction time between incongruent [e.g., a physically large 2 and a physically small 4] and congruent [e.g., a physically small 2 and a physically large 4] conditions), and no facilitation (neutral [e.g., a physically small 2 and a physically large 2] versus congruent) [3]. Previous imaging studies determined the intraparietal sulcus (IPS) as a central area for numerical processing [4-11]. A few studies tried to identify the brain dysfunction underlying developmental dyscalculia but yielded mixed results regarding the involvement of the left [12] or the right [13] IPS. Here we applied fMRI-guided TMS neuronavigation to disrupt left- or right-IPS activation clusters in order to induce dyscalculic-like behavioral deficits in healthy volunteers. Automatic magnitude processing was impaired only during disruption of right-IPS activity. When using the identical paradigm with dyscalculic participants, we reproduced a result pattern similar to that obtained with nondyscalculic volunteers during right-IPS disruption. These findings provide direct evidence for the functional role of right IPS in automatic magnitude processing.

An event-related brain potentials (ERP) experiment was carried out to investigate the influence of semantic category membership on syntactic decision-making. Native speakers of German viewed a series of words that were semantically marked or unmarked for gender and made go/no-go decisions about the grammatical gender of those words. The electrophysiological results indicated that participants could make a gender decision earlier when words were semantically gender-marked than when they were semantically gender-unmarked. Our data provide evidence for the influence of semantic category membership on the decision of the syntactic gender of a visually presented German noun. More specifically, our results support models of language comprehension in which semantic information processing of words is initiated prior to syntactic information processing is finalized.