Neural mechanisms underlying improved new-word learning with high-density transcranial direct current stimulation.

Neurobehavioral studies have provided evidence for the effectiveness of anodal tDCS on language production, by stimulation of the left Inferior Frontal Gyrus (IFG) or of left Temporo-Parietal Junction (TPJ). However, tDCS is currently not used in clinical practice outside of trials, because behavioral effects have been inconsistent and underlying neural effects unclear. Here, we propose to elucidate the neural correlates of verb and noun learning and to determine if they can be modulated with anodal high-definition (HD) tDCS stimulation. Thirty-six neurotypical participants were randomly allocated to anodal HD-tDCS over either the left IFG, the left TPJ, or sham stimulation. On day one, participants performed a naming task (pre-test). On day two, participants underwent a new-word learning task with rare nouns and verbs concurrently to HD-tDCS for 20 min. The third day consisted of a post-test of naming performance. EEG was recorded at rest and during naming on each day. Verb learning was significantly facilitated by left IFG stimulation. HD-tDCS over the left IFG enhanced functional connectivity between the left IFG and TPJ and this correlated with improved learning. HD-tDCS over the left TPJ enabled stronger local activation of the stimulated area (as indexed by greater alpha and beta-band power decrease) during naming, but this did not translate into better learning. Thus, tDCS can induce local activation or modulation of network interactions. Only the enhancement of network interactions, but not the increase in local activation, leads to robust improvement of word learning. This emphasizes the need to develop new neuromodulation methods influencing network interactions. Our study suggests that this may be achieved through behavioral activation of one area and concomitant activation of another area with HD-tDCS.

tDCS of right-hemispheric Wernicke's area homologue affects contextual learning of novel lexicon.

Numerous studies have shown robust evidence of the right hemisphere's involvement in the language function, for instance in the processing of intonation, grammar, word meanings, metaphors, etc. However, its role in lexicon acquisition remains obscure. We applied transcranial direct current stimulation (tDCS) over the right-hemispheric homologue of Wernicke's area to assess its putative involvement in the processing of different types of novel semantics. After receiving 15 min of anodal, cathodal, or sham (placebo) tDCS, three groups of healthy participants learnt novel concrete and abstract words in the context of short stories. Learning outcomes were assessed using a battery of tests immediately after this contextual learning session and 24 h later. As a result, an inhibitory effect of cathodal tDCS and a facilitatory effect of anodal tDCS were found for abstract word acquisition only. We also found a significant drop in task performance on the second day of the assessment for both word types in all the stimulation groups, suggesting no significant influence of tDCS on the post-learning consolidation of new memory traces. The results suggest an involvement of Wernicke's right-hemispheric counterpart in initial encoding (but not consolidation) of abstract semantics, which may be explained either by the right hemispheres direct role in processing lexical semantics or by an indirect impact of tDCS on contralateral (left-hemispheric) cortical areas through cross-callosal connections.

Measuring visual perspective taking in the brain with avatars and arrows: Which question are we asking?

There is an ongoing debate about the involvement of Theory of Mind (ToM) processes in Visual Perspective Taking (VPT). In an fMRI study (Schurz et al., 2015), we borrowed the positive features from a novel VPT task - which is widely used in behavioral research - to study previously overlooked experimental factors in neuroimaging studies. However, as Catmur et al. (2016) rightly argue in a comment on our work, our data do not speak strongly to questions discussed in the original behavioral studies, in particular the issue of implicit mentalizing. We appreciate the clarification of these interpretational limitations of our study, but would like to point out the differences between questions emerging from behavioral and neuroimaging research on VPT. Different from what Catmur et al. (2016) discuss, our study was not intended as a test of implicit mentalizing. In fact, the terms "automatic" and "implicit mentalizing" were never mentioned in our manuscript. Our study addressed a methodological gap between ToM and VPT research, which we identified in two previous meta-analyses on the topics (Schurz et al., 2013, 2014). With this difference in mind we show that the critical points levelled by Catmur et al. (2016) cease to apply.

Neural Correlates of Spatial Attention and Target Detection in a Multi-Target Environment.

Our ability to attend and respond in a multi-target environment is an essential and distinct human skill, as is dramatically demonstrated in stroke patients suffering from extinction. We performed a functional magnetic resonance imaging study to determine the neural anatomy associated with attending and responding to simultaneously presented targets. In healthy subjects, we tested the hypothesis that the right intraparietal sulcus (IPS) is associated both with the top-down direction of attention to multiple target locations and the bottom-up detection of multiple targets, whereas the temporo-parietal junction (TPJ) is predominantly associated with the bottom-up detection of multiple targets. We used a cued target detection task with a high proportion of catch trials to separately estimate top-down cue-related and bottom-up target-related neural activity. Both cues and targets could be presented unilaterally or bilaterally. We found no evidence of target-related neural activation specific to bilateral situations in the TPJ, but observed both cue-related and target-related neural activation specific to bilateral situations in the right IPS and target-related neural activity specific to bilateral situations in the right inferior frontal gyrus (IFG). We conclude that the IPS and the IFG of the right hemisphere underlie our ability to attend and respond in a multi-target environment.

Heterogeneity of social cognition between visual perspective-taking and theory of mind in the temporo-parietal junction.

Visual perspective taking (VPT), particularly level 2 VPT (VPT2), which allows an individual to understand that the same object can be seen differently by others, is related to the theory of mind (ToM), because both functions require a decoupled representation from oneself. Although previous neuroimaging studies have shown that VPT2 and ToM activate the temporo-parietal junction (TPJ), it is unclear whether common neural substrates are involved in both functions. To clarify this point, we directly compared the TPJ activation patterns of individual participants performing VPT2 and ToM tasks using functional magnetic resonance imaging and within-subjects design. A whole-brain analysis revealed that VPT2 and ToM activated overlapping areas in the posterior part of the TPJ. In addition, we found that both the peak coordinates and activated regions for ToM were located significantly more anteriorly and dorsally within the bilateral TPJ than those measured during the VPT2 task. We further confirmed that these activated areas were spatially distinct from the nearby extrastriate body area (EBA), visual motion area (MT+), and the posterior superior temporal sulcus (pSTS) using independent localizer scans. Our findings revealed that VPT2 and ToM have gradient representations, indicating the functional heterogeneity of social cognition within the TPJ.

Watching the Effects of Gravity. Vestibular Cortex and the Neural Representation of "Visual" Gravity.

Gravity is a physical constraint all terrestrial species have adapted to through evolution. Indeed, gravity effects are taken into account in many forms of interaction with the environment, from the seemingly simple task of maintaining balance to the complex motor skills performed by athletes and dancers. Graviceptors, primarily located in the vestibular otolith organs, feed the Central Nervous System with information related to the gravity acceleration vector. This information is integrated with signals from semicircular canals, vision, and proprioception in an ensemble of interconnected brain areas, including the vestibular nuclei, cerebellum, thalamus, insula, retroinsula, parietal operculum, and temporo-parietal junction, in the so-called vestibular network. Classical views consider this stage of multisensory integration as instrumental to sort out conflicting and/or ambiguous information from the incoming sensory signals. However, there is compelling evidence that it also contributes to an internal representation of gravity effects based on prior experience with the environment. This a priori knowledge could be engaged by various types of information, including sensory signals like the visual ones, which lack a direct correspondence with physical gravity. Indeed, the retinal accelerations elicited by gravitational motion in a visual scene are not invariant, but scale with viewing distance. Moreover, the "visual" gravity vector may not be aligned with physical gravity, as when we watch a scene on a tilted monitor or in weightlessness. This review will discuss experimental evidence from behavioral, neuroimaging (connectomics, fMRI, TMS), and patients' studies, supporting the idea that the internal model estimating the effects of gravity on visual objects is constructed by transforming the vestibular estimates of physical gravity, which are computed in the brainstem and cerebellum, into internalized estimates of virtual gravity, stored in the vestibular cortex. The integration of the internal model of gravity with visual and non-visual signals would take place at multiple levels in the cortex and might involve recurrent connections between early visual areas engaged in the analysis of spatio-temporal features of the visual stimuli and higher visual areas in temporo-parietal-insular regions.

Trunk rotation and handedness modulate cortical activation in neglect-associated regions during temporal order judgments.

The rotation of the trunk around its vertical midline could be shown to bias visuospatial temporal judgments towards targets in the hemifield ipsilateral to the trunk orientation and to improve visuospatial performance in patients with visual neglect. However, the underlying brain mechanisms are not well understood. Therefore, the goal of the present study was to investigate the neural effects associated with egocentric midplane shifts under consideration of individual handedness. We employed a visuospatial temporal order judgment (TOJ) task in healthy right- and left-handed subjects while their trunk rotation was varied. Participants responded by a saccade towards the stimulus perceived first out of two stimuli presented with different stimulus onset asynchronies (SOA). Apart from gaze behavior, BOLD-fMRI responses were measured using functional magnetic resonance imaging (fMRI). Based on findings from spatial neglect research, analyses of fMRI-BOLD responses were focused on a bilateral fronto-temporo-parietal network comprising Brodmann areas 22, 39, 40, and 44, as well as the basal ganglia core nuclei (caudate, putamen, pallidum). We observed an acceleration of saccadic speed towards stimuli ipsilateral to the trunk orientation modulated by individual handedness. Left-handed participants showed the strongest behavioral and neural effects, suggesting greater susceptibility to manipulations of trunk orientation. With respect to the dominant hand, a rotation around the vertical trunk midline modulated the activation of an ipsilateral network comprising fronto-temporo-parietal regions and the putamen with the strongest effects for saccades towards the hemifield opposite to the dominant hand. Within the investigated network, the temporo-parietal junction (TPJ) appears to serve as a region integrating sensory, motor, and trunk position information. Our results are discussed in the context of gain modulatory and laterality effects.

Using tDCS to Explore the Role of the Right Temporo-Parietal Junction in Theory of Mind and Cognitive Empathy.

The right temporo-parietal junction (rTPJ) is thought to be closely related to theory of mind (ToM) and cognitive empathy. In the present study, we investigated whether these socio-cognitive abilities could be modulated with non-invasive transcranial direct current stimulation (tDCS) of the rTPJ. Participants received anodal (excitatory), cathodal (inhibitory), or sham stimulation before performing a social cognitive task which included inferring other's intention (the ToM condition) and inferring other's emotion (the cognitive empathy condition). Our results showed that the accuracy of both ToM and cognitive empathy decreased after receiving the cathodal stimulation, suggesting that altering the cortical excitability in the rTPJ could influence human's socio-cognitive abilities. The results of this study emphasize the critical role of the rTPJ in ToM and cognitive empathy and demonstrate that these socio-cognitive abilities could be modulated by the tDCS.

Rhythm makes the world go round: An MEG-TMS study on the role of right TPJ theta oscillations in embodied perspective taking.

While some aspects of social processing are shared between humans and other species, some aspects are not. The former seems to apply to merely tracking another's visual perspective in the world (i.e., what a conspecific can or cannot perceive), while the latter applies to perspective taking in form of mentally "embodying" another's viewpoint. Our previous behavioural research had indicated that only perspective taking, but not tracking, relies on simulating a body schema rotation into another's viewpoint. In the current study we employed Magnetoencephalography (MEG) and revealed that this mechanism of mental body schema rotation is primarily linked to theta oscillations in a wider brain network of body-schema, somatosensory and motor-related areas, with the right posterior temporo-parietal junction (pTPJ) at its core. The latter was reflected by a convergence of theta oscillatory power in right pTPJ obtained by overlapping the separately localised effects of rotation demands (angular disparity effect), cognitive embodiment (posture congruence effect), and basic body schema involvement (posture relevance effect) during perspective taking in contrast to perspective tracking. In a subsequent experiment we interfered with right pTPJ processing using dual pulse Transcranial Magnetic Stimulation (dpTMS) and observed a significant reduction of embodied processing. We conclude that right TPJ is the crucial network hub for transforming the embodied self into another's viewpoint, body and/or mind, thus, substantiating how conflicting representations between self and other may be resolved and potentially highlighting the embodied origins of high-level social cognition in general.

Love-related changes in the brain: a resting-state functional magnetic resonance imaging study.

Romantic love is a motivational state associated with a desire to enter or maintain a close relationship with a specific other person. Functional magnetic resonance imaging (fMRI) studies have found activation increases in brain regions involved in the processing of reward, motivation and emotion regulation, when romantic lovers view photographs of their partners. However, not much is known about whether romantic love affects the brain's functional architecture during rest. In the present study, resting state functional magnetic resonance imaging (rsfMRI) data was collected to compare the regional homogeneity (ReHo) and functional connectivity (FC) across an "in-love" group (LG, N = 34, currently intensely in love), an "ended-love" group (ELG, N = 34, ended romantic relationship recently), and a "single" group (SG, N = 32, never fallen in love). Results show that: (1) ReHo of the left dorsal anterior cingulate cortex (dACC) was significantly increased in the LG (in comparison to the ELG and the SG); (2) ReHo of the left dACC was positively correlated with length of time in love in the LG, and negatively correlated with the lovelorn duration since breakup in the ELG; (3) FC within the reward, motivation, and emotion regulation network (dACC, insula, caudate, amygdala, and nucleus accumbens) as well as FC in the social cognition network [temporo-parietal junction (TPJ), posterior cingulate cortex (PCC), medial prefrontal cortex (MPFC), inferior parietal, precuneus, and temporal lobe] was significantly increased in the LG (in comparison to the ELG and SG); (4) in most regions within both networks FC was positively correlated with the duration of love in the LG but negatively correlated with the lovelorn duration of time since breakup in the ELG. This study provides first empirical evidence of love-related alterations in brain functional architecture. Furthermore, the results shed light on the underlying neural mechanisms of romantic love, and demonstrate the possibility of applying a resting-state fMRI approach for investigating romantic love.

Cognitive functions of the posterior parietal cortex: top-down and bottom-up attentional control.

Although much less is known about human parietal cortex than that of homologous monkey cortex, recent studies, employing neuroimaging, and neuropsychological methods, have begun to elucidate increasingly fine-grained functional and structural distinctions. This review is focused on recent neuroimaging and neuropsychological studies elucidating the cognitive roles of dorsal and ventral regions of parietal cortex in top-down and bottom-up attentional orienting, and on the interaction between the two attentional allocation mechanisms. Evidence is reviewed arguing that regions along the dorsal areas of the parietal cortex, including the superior parietal lobule (SPL) are involved in top-down attentional orienting, while ventral regions including the temporo-parietal junction (TPJ) are involved in bottom-up attentional orienting.