Transcranial Direct Current Stimulation Over the Prefrontal Cortex in Depression Modulates Cortical Excitability in Emotion Regulation Regions as Measured by Concurrent Functional Magnetic Resonance Imaging: An Exploratory Study.

BACKGROUND: A well-established impaired top-down network for effortful emotion regulation (ER) in major depressive disorder (MDD) includes the dorsal and ventromedial prefrontal cortex (PFC) and the amygdala. Transcranial direct current stimulation (tDCS) is a noninvasive neuromodulation method that has been used successfully to induce mood changes in MDD. Despite reliable findings, little is known regarding the precise effects of tDCS on cortical excitability in vivo in depression and how such changes relate to ER. Here, we addressed this question by combining-for the first time in a psychiatric sample-tDCS with functional magnetic resonance imaging in a single-blind randomized design. METHODS: We applied anodal tDCS over the left PFC (area F3 per the 10/20 system) together with cathodal tDCS over the right PFC (F4) or sham tDCS during functional magnetic resonance imaging in patients with moderate to severe MDD (n = 20) and gender- and age-matched control subjects (n = 20). Participants performed 2 runs of an ER task prior to tDCS and 2 runs of the task during tDCS, which was administered at 1.5 mA with 5-cm × 5-cm electrodes. RESULTS: Whole-brain, region of interest, and connectivity analyses revealed an impaired ER network in patients with MDD prior to stimulation. Active anodal tDCS over the left (with concurrent cathodal stimulation of the right) PFC during reappraisal of negative stimuli upregulated activity in ventromedial PFC, which was predictive of gains in reappraisal performance during stimulation for the patients with MDD. CONCLUSIONS: The results of this study offer insights into the mechanisms of action of tDCS and support its potential as a treatment for depression.

Effects of unilateral tDCS over left prefrontal cortex on emotion regulation in depression: Evidence from concurrent functional magnetic resonance imaging.

Major depressive disorder (MDD) is the most common mood disorder and a primary cause of disability worldwide. MDD symptomatology entails disturbances in emotion regulation, namely one's ability to modify the intensity and duration of emotional reactions towards affective events. Transcranial direct current stimulation (tDCS) has emerged as a promising treatment for MDD. Yet, positive tDCS outcomes vary across studies, while the precise effects of the procedure for cortical excitability in MDD during emotion regulation remain largely unexplored. Here, we leveraged functional magnetic resonance imaging (fMRI)-compatible tDCS technology to examine the functional consequences of a unilateral anodal tDCS montage at 1.5 mA over left PFC (area F3; with the reference electrode over an extracephalic location) for brain activity during an emotion-regulation task in MDD patients and age-matched healthy control subjects. Our results revealed down-regulation of negative emotions in the right amygdala and visual cortex of healthy controls but not MDD patients prior to stimulation, the degree of which correlated with the magnitude of the participants' reappraisal scores. TDCS did not elicit significant changes in neural activation patterns for either group. These findings contribute to the literature on the pathophysiology of MDD by showing that a key disturbance in the disorder entails the ineffective down-regulation of activity not only within the amygdala, but also within visual cortical areas in response to negative information. Further, these results suggest that relative to bifrontal tDCS montages, unilateral stimulation of moderate intensity over left PFC may not be sufficient to elicit therapeutic effects for MDD.

Differences in brain activity patterns during creative idea generation between eminent and non-eminent thinkers.

An influential model of the neural mechanisms of creative thought suggests that creativity is manifested in the joint contributions of the Default Mode Network (DMN; a set of regions in the medial PFC, lateral and medial parietal cortex, and the medial temporal lobes) and the executive networks within the dorsolateral PFC. Several empirical reports have offered support for this model by showing that complex interactions between these brain systems account for individual differences in creative performance. The present study examined whether the engagement of these regions in idea generation is modulated by one's eminence in a creativity-related field. Twenty (n â€‹= â€‹20) healthy eminent creators from diverse fields of expertise and a 'smart' comparison group of sixteen (n â€‹= â€‹16) age- and education-matched non-eminent thinkers were administered a creative generation task (an adaptation of the Alternative Uses Task) and a control perceptual task, while undergoing functional magnetic resonance imaging (fMRI). The participants' verbal responses were recorded through a noise-canceling microphone and were later coded for fluency and accuracy. Behavioral and fMRI analyses revealed commonalities between groups, but also distinct patterns of activation in default mode and executive brain regions between the eminent and the non-eminent participants during creative thinking. We interpret these findings in the context of the well-documented contributions of these regions in the generation of creative ideas as modulated, in this study, by participants' creative eminence.

Distinct neural mechanisms underlying conceptual knowledge of manner and instrument verbs.

Studies on the organization of conceptual knowledge have examined categories of concrete nouns extensively. Less is known about the neural basis of verb categories suggested by linguistic theories. We used functional MRI to examine the differences between manner verbs, which encode information about the manner of an action, versus instrument verbs, which encode information about an object as part of their meaning. Using both visual and verbal stimuli and a combination of univariate and multivariate pattern analyses, our results show that accessing conceptual representations of instrument class involves brain regions typically associated with complex action and object perception, including the anterior inferior parietal cortex and occipito-temporal cortex. On the other hand, accessing conceptual representations of the manner class involves regions that are commonly associated with the processing of visual and biological motion, in the posterior superior temporal sulcus. These findings support the idea that the semantics of manner and instrument verbs are supported by distinct neural mechanisms.

The multifaceted abstract brain.

concepts play a central role in human behaviour and constitute a critical component of the human conceptual system. Here, we investigate the neural basis of four types of abstract concepts, examining their similarities and differences through neuroimaging meta-analyses. We examine numerical and emotional concepts, and two higher-order abstract processes, morality judgements and theory of mind. Three main findings emerge. First, representation of abstract concepts is more widespread than is often assumed. Second, representations of different types of abstract concepts differ in important respects. Each of the domains examined here was associated with some unique areas. Third, some areas were commonly activated across domains and included inferior parietal, posterior cingulate and medial prefrontal cortex. We interpret these regions in terms of their role in episodic recall, event representation and social-emotional processing. We suggest that different types of abstract concepts can be represented and grounded through differing contributions from event-based, interoceptive, introspective and sensory-motor representations. The results underscore the richness and diversity of abstract concepts, argue against single-mechanism accounts for representation of all types of abstract concepts and suggest mechanisms for their direct and indirect grounding.This article is part of the theme issue 'Varieties of abstract concepts: development, use and representation in the brain'.

Impaired Comprehension of Speed Verbs in Parkinson's Disease.

OBJECTIVES: A wealth of studies provide evidence for action simulation during language comprehension. Recent research suggests such action simulations might be sensitive to fine-grained information, such as speed. Here, we present a crucial test for action simulation of speed in language by assessing speed comprehension in patients with Parkinson's disease (PD). Based on the patients' motor deficits, we hypothesized that the speed of motion described in language would modulate their performance in semantic tasks. Specifically, they would have more difficulty processing language about relatively fast speed than language about slow speed. METHODS: We conducted a semantic similarity judgment task on fast and slow action verbs in patients with PD and age-matched healthy controls. Participants had to decide which of two verbs most closely matched a target word. RESULTS: Compared to controls, PD patients were slower making judgments about fast action verbs, but not for judgments about slow action verbs, suggesting impairment in processing language about fast action. Moreover, this impairment was specific to verbs describing fast action performed with the hand. CONCLUSIONS: Problems moving quickly lead to difficulties comprehending language about moving quickly. This study provides evidence that speed is an important part of action representations. (JINS, 2017, 23, 412-420).

Effects of motion speed in action representations.

Grounded cognition accounts of semantic representation posit that brain regions traditionally linked to perception and action play a role in grounding the semantic content of words and sentences. Sensory-motor systems are thought to support partially abstract simulations through which conceptual content is grounded. However, which details of sensory-motor experience are included in, or excluded from these simulations, is not well understood. We investigated whether sensory-motor brain regions are differentially involved depending on the speed of actions described in a sentence. We addressed this issue by examining the neural signature of relatively fast (The old lady scurried across the road) and slow (The old lady strolled across the road) action sentences. The results showed that sentences that implied fast motion modulated activity within the right posterior superior temporal sulcus and the angular and middle occipital gyri, areas associated with biological motion and action perception. Sentences that implied slow motion resulted in greater signal within the right primary motor cortex and anterior inferior parietal lobule, areas associated with action execution and planning. These results suggest that the speed of described motion influences representational content and modulates the nature of conceptual grounding. Fast motion events are represented more visually whereas motor regions play a greater role in representing conceptual content associated with slow motion.

Embodied Simulations Are Modulated by Sentential Perspective.

There is considerable evidence that language comprehenders derive lexical-semantic meaning by mentally simulating perceptual and motor attributes of described events. However, the nature of these simulations-including the level of detail that is incorporated and contexts under which simulations occur-is not well understood. Here, we examine the effects of first- versus third-person perspective on mental simulations during sentence comprehension. First-person sentences describing physical transfer towards or away from the body (e.g., "You threw the microphone," "You caught the microphone") modulated response latencies when responses were made along a front-back axis, consistent with the action-sentence compatibility effect (ACE). This effect was not observed for third-person sentences ("He threw the microphone," "He caught the microphone"). The ACE was observed when making responses along a left-right axis for third-person, but not first-person sentences. Abstract sentences (e.g., "He heard the message") did not show an ACE along either axis. These results show that perspective is a detail that is simulated during action sentence comprehension, and that motoric activations are flexible and affected by the pronominal perspective used in the sentence.

The Semantics of Syntax: The Grounding of Transitive and Intransitive Constructions.

Embodied theories of language maintain that brain areas associated with perception and action are also involved in the processing and representation of word meaning. A number of studies have shown that sentences with action verbs elicit activation within sensory-motor brain regions, arguing that sentence-induced mental simulations provide a means for grounding their lexical-semantic meaning. Constructionist theories argue, however, that form-meaning correspondence is present not only at the lexical level but also at the level of constructions. We investigated whether sentence-induced motor resonance is present for syntactic constructions. We measured the BOLD signal while participants read sentences with (di)transitive (caused motion) or intransitive constructions that contained either action or abstract verbs. The results showed a distinct neuronal signature for caused motion and intransitive syntactic frames. Caused motion frames activated regions associated with reaching and grasping actions, including the left anterior intraparietal sulcus and the parietal reach region. Intransitive frames activated lateral temporal regions commonly associated with abstract word processing. The left pars orbitalis showed an interaction between the syntactic frame and verb class. These findings show that sensory-motor activation elicited by sentences entails both motor resonance evoked by single words as well as at the level of syntactic constructions.

Resting state signatures of domain and demand-specific working memory performance.

Working memory (WM) is one of the key constructs in understanding higher-level cognition. We examined whether patterns of activity in the resting state of individual subjects are correlated with their off-line working and short-term memory capabilities. Participants completed a resting-state fMRI scan and off-line working and short-term memory (STM) tests with both verbal and visual materials. We calculated fractional amplitude of low frequency fluctuations (fALFF) from the resting state data, and also computed connectivity between seeds placed in frontal and parietal lobes. Correlating fALFF values with behavioral measures showed that the fALFF values in a widespread fronto-parietal network during rest were positively correlated with a combined memory measure. In addition, STM showed a significant correlation with fALFF within the right angular gyrus and left middle occipital gyrus, whereas WM was correlated with fALFF values within the right IPS and left dorsomedial cerebellar cortex. Furthermore, verbal and visuospatial memory capacities were associated with dissociable patterns of low-frequency fluctuations. Seed-based connectivity showed correlations with the verbal WM measure in the left hemisphere, and with the visual WM measure in the right hemisphere. These findings contribute to our understanding of how differences in spontaneous low-frequency fluctuations at rest are correlated with differences in cognitive performance.

Familiarity differentially affects right hemisphere contributions to processing metaphors and literals.

The role of the two hemispheres in processing metaphoric language is controversial. While some studies have reported a special role of the right hemisphere (RH) in processing metaphors, others indicate no difference in laterality relative to literal language. Some studies have found a role of the RH for novel/unfamiliar metaphors, but not conventional/familiar metaphors. It is not clear, however, whether the role of the RH is specific to metaphor novelty, or whether it reflects processing, reinterpretation or reanalysis of novel/unfamiliar language in general. Here we used functional magnetic resonance imaging (fMRI) to examine the effects of familiarity in both metaphoric and non-metaphoric sentences. A left lateralized network containing the middle and inferior frontal gyri, posterior temporal regions in the left hemisphere (LH), and inferior frontal regions in the RH, was engaged across both metaphoric and non-metaphoric sentences; engagement of this network decreased as familiarity decreased. No region was engaged selectively for greater metaphoric unfamiliarity. An analysis of laterality, however, showed that the contribution of the RH relative to that of LH does increase in a metaphor-specific manner as familiarity decreases. These results show that RH regions, taken by themselves, including commonly reported regions such as the right inferior frontal gyrus (IFG), are responsive to increased cognitive demands of processing unfamiliar stimuli, rather than being metaphor-selective. The division of labor between the two hemispheres, however, does shift towards the right for metaphoric processing. The shift results not because the RH contributes more to metaphoric processing. Rather, relative to its contribution for processing literals, the LH contributes less.

Flexibility in embodied language processing: context effects in lexical access.

According to embodied theories of language (ETLs), word meaning relies on sensorimotor brain areas, generally dedicated to acting and perceiving in the real world. More specifically, words denoting actions are postulated to make use of neural motor areas, while words denoting visual properties draw on the resources of visual brain areas. Therefore, there is a direct correspondence between word meaning and the experience a listener has had with a word's referent on the brain level. Behavioral and neuroimaging studies have provided evidence in favor of ETLs; however, recent studies have also shown that sensorimotor information is recruited in a flexible manner during language comprehension (e.g., Raposo et al.; Van Dam et al.,), leaving open the question as to what level of language processing sensorimotor activations contribute. In this study, we investigated the time course of modality-specific contributions (i.e., the contribution of action information) as to word processing by manipulating both (a) the linguistic and (b) the action context in which target words were presented. Our results demonstrate that processes reflecting sensorimotor information play a role early in word processing (i.e., within 200 ms of word presentation), but that they are sensitive to the linguistic context in which a word is presented. In other words, when sensorimotor information is activated, it is activated quickly; however, specific words do not reliably activate a consistent sensorimotor pattern.

Embodied grounding of memory: toward the effects of motor execution on memory consolidation.

Behavioural and neuroscientific research has provided evidence for a strong functional link between the neural motor system and lexical-semantic processing of action-related language. It remains unclear, however, whether the impact of motor actions is restricted to online language comprehension or whether sensorimotor codes are also important in the formation and consolidation of persisting memory representations of the word's referents. The current study now demonstrates that recognition performance for action words is modulated by motor actions performed during the retention interval. Specifically, participants were required to learn words denoting objects that were associated with either a pressing or a twisting action (e.g., piano, screwdriver) and words that were not associated to actions. During a 6-8-minute retention phase, participants performed an intervening task that required the execution of pressing or twisting responses. A subsequent recognition task revealed a better memory for words that denoted objects for which the functional use was congruent with the action performed during the retention interval (e.g., pepper mill-twisting action, doorbell-pressing action) than for words that denoted objects for which the functional use was incongruent. In further experiments, we were able to generalize this effect of selective memory enhancement of words by performing congruent motor actions to an implicit perceptual (Experiment 2) and implicit semantic memory test (Experiment 3). Our findings suggest that a reactivation of motor codes affects the process of memory consolidation and emphasizes therefore the important role of sensorimotor codes in establishing enduring semantic representations.

Context-dependent changes in functional connectivity of auditory cortices during the perception of object words.

Embodied theories hold that cognitive concepts are grounded in our sensorimotor systems. Specifically, a number of behavioral and neuroimaging studies have buttressed the idea that language concepts are represented in areas involved in perception and action [Pulvermueller, F. Brain mechanisms linking language and action. Nature Reviews Neuroscience, 6, 576-582, 2005; Barsalou, L. W. Perceptual symbol systems. Behavioral and Brain Sciences, 22, 577-660, 1999]. Proponents of a strong embodied account argue that activity in perception/action areas is triggered automatically upon encountering a word and reflect static semantic representations. In contrast to what would be expected if lexical semantic representations are automatically triggered upon encountering a word, a number of studies failed to find motor-related activity for words with a putative action-semantic component [Raposo, A., Moss, H. E., Stamatakis, E. A., & Tyler, L. K. Modulation of motor and premotor cortices by actions, action words and action sentences. Neuropsychologia, 47, 388-396, 2009; Rueschemeyer, S.-A., Brass, M., & Friederici, A. D. Comprehending prehending: Neural correlates of processing verbs with motor stems. Journal of Cognitive Neuroscience, 19, 855-865, 2007]. In a recent fMRI study, Van Dam and colleagues [Van Dam, W. O., Van Dijk, M., Bekkering, H., & Rueschemeyer, S.-A. Flexibility in embodied lexical-semantic representations. Human Brain Mapping, in press] showed that the degree to which a modality-specific region contributes to a representation considerably changes as a function of context. In the current study, we presented words for which both motor and visual properties (e.g., tennis ball, boxing glove) were important in constituting the concept. Our aim was to corroborate on earlier findings of flexible and context-dependent language representations by testing whether functional integration between auditory brain regions and perception/action areas is modulated by context. Functional connectivity was investigated by means of a psychophysiological interaction analysis, in which we found that bilateral superior temporal gyrus was more strongly connected with brain regions relevant for coding action information: (1) for Action Color words vs. Abstract words, and (2) for Action Color words presented in a context that emphasized action vs. a context that emphasized color properties.

Flexibility in embodied lexical-semantic representations.

According to an embodied view of language comprehension, language concepts are grounded in our perceptual systems. Evidence for the idea that concepts are grounded in areas involved in action and perception comes from both behavioral and neuroimaging studies (Glenberg [1997]: Behav Brain Sci 20:1-55; Barsalou [1999]: Behav Brain Sci 22:577-660; Pulvermueller [1999]: Behav Brain Sci 22:253-336; Barsalou et al. [2003]: Trends Cogn Sci 7:84-91). However, the results from several studies indicate that the activation of information in perception and action areas is not a purely automatic process (Raposo et al. [2009]: Neuropsychologia 47:388-396; Rueschemeyer et al. [2007]: J Cogn Neurosci 19:855-865). These findings suggest that embodied representations are flexible. In these studies, flexibility is characterized by the relative presence or absence of activation in our perceptual systems. However, even if the context in which a word is presented does not undermine a motor interpretation, it is possible that the degree to which a modality-specific region contributes to a representation depends on the context in which conceptual features are retrieved. In the present study, we investigated this issue by presenting word stimuli for which both motor and visual properties (e.g., Tennis ball, Boxing glove) were important in constituting the concept. Conform with the idea that language representations are flexible and context dependent, we demonstrate that the degree to which a modality-specific region contributes to a representation considerably changes as a function of context.

Mental rotation impairs attention shifting and short-term memory encoding: neurophysiological evidence against the response-selection bottleneck model of dual-task performance.

Dual tasks and their associated delays have often been used to examine the boundaries of processing in the brain. We used the dual-task procedure and recorded event-related potentials (ERPs) to investigate how mental rotation of a first stimulus (S1) influences the shifting of visual-spatial attention to a second stimulus (S2). Visual-spatial attention was monitored by using the N2pc component of the ERP. In addition, we examined the sustained posterior contralateral negativity (SPCN) believed to index the retention of information in visual short-term memory. We found modulations of both the N2pc and the SPCN, suggesting that engaging mechanisms of mental rotation impairs the deployment of visual-spatial attention and delays the passage of a representation of S2 into visual short-term memory. Both results suggest interactions between mental rotation and visual-spatial attention in capacity-limited processing mechanisms indicating that response selection is not pivotal in dual-task delays and all three processes are likely to share a common resource like executive control.

Action-effect binding by observational learning.

The acquisition of bidirectional action-effect associations plays a central role in the ability to intentionally control actions. Humans learn about actions not only through active experience, but also through observing the actions of others. In Experiment 1, we examined whether action-effect associations can be acquired by observational learning. To this end, participants observed how a model repeatedly pressed two buttons during an observation phase. Each of the buttonpresses led to a specific tone (action effect). In a subsequent test phase, the tones served as target stimuli to which the participants had to respond with buttonpresses. Reaction times were shorter if the stimulus-response mapping in the test phase was compatible with the action-effect association in the observation phase. Experiment 2 excluded the possibility that the impact of perceived action effects on own actions was driven merely by an association of spatial features with the particular tones. Furthermore, we demonstrated that the presence of an agent is necessary to acquire novel action-effect associations through observation. Altogether, the study provides evidence for the claim that bidirectional action-effect associations can be acquired by observational learning. Our findings are discussed in the context of the idea that the acquisition of action-effect associations through observation is an important cognitive mechanism subserving the human ability for social learning.

How object-specific are object files? Evidence for integration by location.

Given the distributed representation of visual features in the human brain, binding mechanisms are necessary to integrate visual information about the same perceptual event. It has been assumed that feature codes are bound into object files--pointers to the neural codes of the features of a given event. The present study investigated the perceptual criteria underlying integration into an object file. Previous studies confounded the sharing of spatial location with belongingness to the same perceptual object, 2 factors we tried to disentangle. Our findings suggest that orientation and color features appearing in a task-irrelevant preview display were integrated irrespective of whether they appeared as part of the same object or of different objects (e.g., 1 stationary and the other moving continuously, or a banana in a particular orientation overlaying an apple of a particular color). In contrast, integration was markedly reduced when the 2 objects were separated in space. Taken together, these findings suggest that spatial overlap of visual features is a sufficient criterion for integrating them into the same object file.

How specifically are action verbs represented in the neural motor system: an fMRI study.

Embodied accounts of language processing suggest that sensorimotor areas, generally dedicated to perception and action, are also involved in the processing and representation of word meaning. Support for such accounts comes from studies showing that language about actions selectively modulates the execution of congruent and incongruent motor responses (e.g., Glenberg & Kaschak, 2002), and from functional neuroimaging studies showing that understanding action-related language recruits sensorimotor brain areas (e.g. Hauk, Johnsrude, & Pulvermueller, 2004). In the current experiment we explored the basis of the neural motor system's involvement in representing words denoting actions. Specifically, we investigated whether the motor system's involvement is modulated by the specificity of the kinematics associated with a word. Previous research in the visual domain indicates that words denoting basic level category members lacking a specific form (e.g., bird) are less richly encoded within visual areas than words denoting subordinate level members (e.g., pelican), for which the visual form is better specified (Gauthier, Anderson, Tarr, Skudlarski, & Gore, 1997). In the present study we extend these findings to the motor domain. Modulation of the BOLD response elicited by verbs denoting a general motor program (e.g., to clean) was compared to modulation elicited by verbs denoting a more specific motor program (e.g., to wipe). Conform with our hypothesis, a region within the bilateral inferior parietal lobule, typically serving the representation of action plans and goals, was sensitive to the specificity of motor programs associated with the action verbs. These findings contribute to the growing body of research on embodied language representations by showing that the concreteness of an action-semantic feature is reflected in the neural response to action verbs.

Effects of intentional motor actions on embodied language processing.

Embodied theories of language processing suggest that this motor simulation is an automatic and necessary component of meaning representation. If this is the case, then language and action systems should be mutually dependent (i.e., motor activity should selectively modulate processing of words with an action-semantic component). In this paper, we investigate in two experiments whether evidence for mutual dependence can be found using a motor priming paradigm. Specifically, participants performed either an intentional or a passive motor task while processing words denoting manipulable and nonmanipulable objects. The performance rates (Experiment 1) and response latencies (Experiment 2) in a lexical-decision task reveal that participants performing an intentional action were positively affected in the processing of words denoting manipulable objects as compared to nonmanipulable objects. This was not the case if participants performed a secondary passive motor action (Experiment 1) or did not perform a secondary motor task (Experiment 2). The results go beyond previous research showing that language processes involve motor systems to demonstrate that the execution of motor actions has a selective effect on the semantic processing of words. We suggest that intentional actions activate specific parts of the neural motor system, which are also engaged for lexical-semantic processing of action-related words and discuss the beneficial versus inhibitory nature of this relationship. The results provide new insights into the embodiment of language and the bidirectionality of effects between language and action processing.