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Body orientation of gesture entails social‐communicative intention, and may thus influence how gestures are perceived and comprehended together with auditory speech during face‐to‐face communication. To date, despite the emergence of neuroscientific literature on the role of body orientation on hand action perception, limited studies have directly investigated the role of body orientation in the interaction between gesture and language. To address this research question, we carried out an electroencephalography (EEG) experiment presenting to participants (n = 21) videos of frontal and lateral communicative hand gestures of 5 s (e.g., raising a hand), followed by visually presented sentences that are either congruent or incongruent with the gesture (e.g., “the mountain is high/low…”). Participants underwent a semantic probe task, judging whether a target word is related or unrelated to the gesture‐sentence event. EEG results suggest that, during the perception phase of handgestures, while both frontal and lateral gestures elicited a power decrease in both the alpha (8–12 Hz) and the beta (16–24 Hz) bands, lateral versus frontal gestures elicited reduced power decrease in the beta band, source‐located to the medial prefrontal cortex. For sentence comprehension, at the critical word whose meaning is congruent/incongruent with the gesture prime, frontal gestures elicited an N400 effect for gesture‐sentence incongruency. More importantly, this incongruency effect was significantly reduced for lateral gestures. These findings suggest that body orientation plays an important role in gesture perception, and that its inferred social‐communicative intention may influence gesture‐language interaction at semantic level., We collected EEG when participants process visual sentences primed by frontal and lateral gestures. Lateral gestures elicited reduced beta band power decrease during perception. Additionally, in the visual sentences, the N400 effect, as derived from semantic incongruency between the critical word and the gesture prime, was reduced for lateral gestures.

The feeling of being addressed is the first step in a complex processing stream enabling successful social communication. Social impairments are a relevant characteristic of patients with major depressive disorder (MDD). Here, we investigated a mechanism which—if impaired—might contribute to withdrawal or isolation in MDD, namely, the neural processing of social cues such as body orientation and gesture. During funtional magnetic resonance imaging (fMRI) data acquisition, 33 patients with MDD and 43 healthy control subjects watched video clips of a speaking actor: one version with a gesture accompanying the speech and one without gesture. Videos were filmed simultaneously from two different viewpoints: one with the actor facing the viewer head‐on (frontal) and one side‐view (lateral). After every clip, the participants were instructed to evaluate whether they felt addressed or not. Despite overall comparable addressment ratings and a large overlap in activation patterns in MDD and healthy subjects for gesture processing, the anterior cingulate cortex, bilateral superior/middle frontal cortex, and right angular gyrus were more strongly activated in patients than in healthy subjects for the frontal conditions. Our analyses revealed that patients showed specifically higher activation than healthy subjects for the frontal condition without gesture in regions including the posterior cingulate cortex, left prefrontal cortex, and the left hippocampus. We conclude that MDD patients can recognize and interpret social cues such as gesture or body orientation; however, they seem to require more neural resources. This additional effort might affect successful communication and contribute to social isolation in MDD.

Gestures are an integral part of in-person conversations and complement the meaning of the speech they accompany. The neural processing of co-speech gestures is supported by a mostly left-lateralized network of fronto-temporal regions. However, in contrast to iconic gestures, metaphoric as well as unrelated gestures have been found to more strongly engage the left and right inferior frontal gyrus (IFG), respectively. With this study, we conducted the first systematic comparison of all three types of gestures and resulting potential laterality effects. During collection of functional imaging data, 74 subjects were presented with 5 s videos of abstract speech with related metaphoric gestures, concrete speech with related iconic gestures and concrete speech with unrelated gestures. They were asked to judge whether the content of the speech and gesture matched or not. Differential contrasts revealed that both abstract related and concrete unrelated compared to concrete related stimuli elicited stronger activation of the bilateral IFG. Analyses of lateralization indices for IFG activation further showed a left hemispheric dominance for metaphoric gestures and a right hemispheric dominance for unrelated gestures. Our results give support to the hypothesis that the bilateral IFG is activated specifically when processing load for speech-gesture combinations is high. In addition, laterality effects indicate a stronger involvement of the right IFG in mismatch detection and conflict processing, whereas the left IFG performs the actual integration of information from speech and gesture.

Humor is a ubiquitous human ability with important implications for both social and emotional functioning. Patients with neuropsychiatric disorders, such as schizophrenia, experience difficulties in the comprehension and appreciation of humor. However, the specific neural mechanisms underlying these deficits are unknown. In the current study, we sought to elucidate the neural correlates of humor processing in patients with schizophrenia spectrum disorders (SSD). Functional Magnetic Resonance Imaging (fMRI) was used in thirty-one patients with SSD and a control group, performing a humor processing paradigm. Both regional brain activation and parametric modulation of brain responses via subjective funniness ratings were collected during the scanning procedure. On a neural level, large overlaps in fronto-temporal brain activation was found in both groups. However, patients compared to healthy control subjects showed attenuated responses in frontal brain regions, including the anterior cingulate cortex, medial prefrontal cortex (mPFC), superior frontal gyrus and middle frontal gyrus, as well as in the striatum (i.e. caudate nucleus, putamen). Furthermore, parametric modulation of subjective funniness ratings resulted in attenuated responses in the mPFC, bilateral insula, and left hippocampus. Analysis of functional connectivity revealed alterations in mPFC-caudate nucleus coupling in patients with SSD, which might reflect impairments in reward-related processing. Notably, alterations in mPFC-caudate nucleus coupling in patients were significantly associated to subjective funniness ratings. Our results extend previous findings demonstrating the relevance of frontal hypoactivation for humor processing impairments in patients with SSD and first point towards alterations in humor appreciation processes.

Schizophrenia is associated with impaired and exaggerated Theory of Mind processes, pointing on alterations in generating a representation of another person's mind. Despite recent work on healthy subjects suggesting that a coupling between the right temporoparietal junction (rTPJ) and the hippocampus is relevant for building representations of others' intentions, the neural basis of related dysfunctions in patients with schizophrenia remains unclear. Therefore, we used structural and functional magnetic resonance imaging together with a modified prisoner's dilemma game to test the hypotheses, that patients show dysfunctional social updating on behavioral level accompanied by altered rTPJ-hippocampus coupling on a functional and a structural level. During the task, 31 patients with schizophrenia and 20 healthy controls interacted with 3 playing partners, who behaved according to stable strategies competitively, cooperatively, or randomly. Our data show that patients adapted their social behavior less flexibly to the playing partners than healthy controls, indicating differences in forming mental representations of the counterparts' intentions. Patients showed lower functional connectivity between the rTPJ and temporal lobe regions such as the hippocampus, the fusiform gyrus, and the middle temporal gyrus, indicating that in patients the rTPJ fails to integrate memory-informed processing streams during mental state inferences. Remarkably, the rTPJ-hippocampus coupling accounted for the participants' adaptive social behavior in the task, suggesting that a neural pathway relevant for updating social knowledge and forming forward predictions in social interactions is altered in schizophrenia.

The semantic integration between gesture and speech (GSI) is mediated by the left posterior temporal sulcus/middle temporal gyrus (pSTS/MTG) and the left inferior frontal gyrus (IFG). Evidence from electroencephalography (EEG) suggests that oscillations in the alpha and beta bands may support processes at different stages of GSI. In the present study, we investigated the relationship between electrophysiological oscillations and blood-oxygen-level-dependent (BOLD) activity during GSI. In a simultaneous EEG-fMRI study, German participants (n = 19) were presented with videos of an actor either performing meaningful gestures in the context of a comprehensible German (GG) or incomprehensible Russian sentence (GR), or just speaking a German sentence (SG). EEG results revealed reduced alpha and beta power for the GG vs. SG conditions, while fMRI analyses showed BOLD increase in the left pSTS/MTG for GG > GR ∩ GG > SG. In time-window-based EEG-informed fMRI analyses, we further found a positive correlation between single-trial alpha power and BOLD signal in the left pSTS/MTG, the left IFG, and several sub-cortical regions. Moreover, the alpha-pSTS/MTG correlation was observed in an earlier time window in comparison to the alpha-IFG correlation, thus supporting a two-stage processing model of GSI. Our study shows that EEG-informed fMRI implies multiple roles of alpha oscillations during GSI, and that the method is a best candidate for multidimensional investigations on complex cognitive functions such as GSI.

Identifying someone else's noncooperative intentions can prevent exploitation in social interactions. Hence, the inference of another person's mental state might be most pronounced in order to improve social decision‐making. Here, we tested the hypothesis that brain regions associated with Theory of Mind (ToM), particularly the right temporo–parietal junction (rTPJ), show higher neural responses when interacting with a selfish person and that the rTPJ‐activity as well as cooperative tendencies will change over time. We used functional magnetic resonance imaging (fMRI) and a modified prisoner's dilemma game in which 20 participants interacted with three fictive playing partners who behaved according to stable strategies either competitively, cooperatively or randomly during seven interaction blocks. The rTPJ and the posterior–medial prefrontal cortex showed higher activity during the interaction with a competitive compared with a cooperative playing partner. Only the rTPJ showed a high response during an early interaction phase, which preceded participants increase in defective decisions. Enhanced functional connectivity between the rTPJ and the left hippocampus suggests that social cognition and learning processes co‐occur when behavioral adaptation seems beneficial.

Previous research and theory implicate that personality traits, such as extraversion and neuroticism, influence the processing of humor, as indicated by alterations in the activation of fronto-temporal and mesocorticolimbic brain regions during humor processing. In the current study, we sought to complement these findings by testing whether inter-individual differences in functional connectivity of humor-related brain regions are modulated by stable personality characteristics during humor processing. Using fMRI techniques, we studied 19 healthy subjects during the processing of standardized humorous and neutral cartoons. In order to isolate the specific effects of humor appreciation, subjective funniness ratings, collected during the scanning procedure, were implemented in the analysis as parametric modulation. Two distinct clusters in the right amygdala and the left insula were identified. Seed-to-voxel connectivity analysis investigating the effects of personality on inter-individual differences in functional connectivity revealed that amygdala and insula connectivity with brain areas previously related to humor comprehension (e.g. middle temporal gyrus) and appreciation (e.g. caudate nucleus) were significantly modulated by personality dimensions. These results underscore the sensitivity of humor processing to moderating influences, such as personality, and call attention to the importance of brain connectivity measures for the investigation of inter-individual differences in the processing of humor.

Structural and functional changes in the lateral temporal language areas have been related to formal thought disorder (FTD) in schizophrenia. Continuous, natural speech production activates the right lateral temporal lobe in schizophrenia, as opposed to the left in healthy subjects. Positive and negative FTD can be elicited in healthy subjects by glutamatergic NMDA blockade with ketamine. It is unclear whether the glutamate system is related to the reversed hemispheric lateralization during speaking in patients. In a double-blind, crossover, placebo-controlled study, 15 healthy, male, right-handed volunteers overtly described 7 pictures for 3 min each while BOLD signal changes were acquired with fMRI. As a measure of linguistic demand, the number of words within 20 s epochs was correlated with BOLD responses. Participants developed S-ketamine-induced psychotic symptoms, particularly positive FTD. Ketamine vs placebo was associated with enhanced neural responses in the right middle and inferior temporal gyri. Similar to a previous fMRI study in schizophrenia patients vs healthy controls applying the same design, S-ketamine reversed functional lateralization during speech production in healthy subjects. Results demonstrate an association between glutamatergic imbalance, dysactivations in lateral temporal brain areas, and FTD symptom formation.

While listening to continuous speech, humans process beat information to correctly identify word boundaries. The beats of language are stress patterns that are created by combining lexical (word-specific) stress patterns and the rhythm of a specific language. Sometimes, the lexical stress pattern needs to be altered to obey the rhythm of the language. This study investigated the interplay of lexical stress patterns and rhythmical well-formedness in natural speech with fMRI. Previous electrophysiological studies on cases in which a regular lexical stress pattern may be altered to obtain rhythmical well-formedness showed that even subtle rhythmic deviations are detected by the brain if attention is directed toward prosody. Here, we present a new approach to this phenomenon by having participants listen to contextually rich stories in the absence of a task targeting the manipulation. For the interaction of lexical stress and rhythmical well-formedness, we found one suprathreshold cluster localized between the cerebellum and the brain stem. For the main effect of lexical stress, we found higher BOLD responses to the retained lexical stress pattern in the bilateral SMA, bilateral postcentral gyrus, bilateral middle fontal gyrus, bilateral inferior and right superior parietal lobule, and right precuneus. These results support the view that lexical stress is processed as part of a sensorimotor network of speech comprehension. Moreover, our results connect beat processing in language to domain-independent timing perception.

© 2019 Elsevier Inc. Gestures are elemental components of social communication and aid comprehension of verbal messages; however, little is known about the potential role of gestures in facilitating processing of semantic complexity in an ecologically valid setting. The goal of this study was to investigate whether cognitive load, as indexed by semantic complexity, is modulated by the presentation of gestures accompanying speech. Twenty healthy participants watched 16 video clips of a short narrative while instructed to carefully listen to and watch the narrator while functional magnetic resonance imaging (fMRI) data were acquired. The videos contained passages with and without various co-speech gestures, as well as passages where the semantic complexity was either low or high, as measured by the metric of idea density. Increasing semantic complexity led to reduced activation within the default mode network (DMN); whereas, presents of gestures decreased activation in language-related regions (left middle temporal gyrus and left inferior frontal gyrus) and increased activation in high-level visual and multimodal regions of occipitotemporal cortex. Most interestingly, an interaction between semantic complexity and gestures was observed in a language-related area in left anterior temporal cortex; specifically, increasing gestures led to a greater drop in activation with high vs. Low semantic complexity. These results provide evidence that the facilitation of gestures on semantic processing, particularly for complex narratives, is reflected in the neural substrates of language processing.

Impairments of social cognition are defined as core features in the pathology of schizophrenia. In a study by Lehmann and colleagues (2014), patients with schizophrenia have been shown to demonstrate a diminished capacity to understand others' emotions (i.e. cognitive empathy), but a preserved ability to share or feel the emotional states of others (i.e. emotional empathy). Here, we report on an independent replication study investigating cognitive and emotional empathy in 35 patients with schizophrenia spectrum disorders and a matched control group, which 1) confirms that patients demonstrate preserved emotional empathy in self-report and behavioural measurements, and 2) reveals associations between emotional empathy and social anhedonia in patients.

Patients with schizophrenia suffer from impairments in the perception and production of gestures. The extent to which patients can access the semantic association between speech and co-verbal gestures in concrete or abstract/metaphorical meaning contexts is unknown. We investigated 1) how patients differ from controls in gesture matching performance, 2) how performance differs in the context of abstract versus concrete meaning, and 3) whether formal thought disorder (FTD) symptom severity predicts task impairment. Forty-five patients with schizophrenia spectrum disorders (two subgroups, mild and severe) took part in this study. Participants were presented with video clips, each showing an actor saying a sentence while producing a gesture. Sentences contained either concrete or abstract/metaphorical information, and the accompanying gesture was either semantically related or unrelated to the sentence. Participants indicated via button press whether the gesture matched the content of the verbal utterance. Both patient subgroups demonstrated reduced performance in all comparisons. A significant interaction was found between patient subgroup and sentence abstractness. Task performance was worst for patients with severe positive FTD symptomatology in the abstract condition, while there were no patient subgroup differences in the concrete condition. These data shed new light on gesture-speech mismatch detection impairments in schizophrenia. Scopus

One of the key features of human interpersonal communication is our ability to integrate information communicated by speech and accompanying gestures. However, it is still not fully understood how this essential combinatory process is represented in the human brain. Functional magnetic resonance imaging (fMRI) studies have unanimously attested the relevance of activation in the posterior superior temporal sulcus/middle temporal gyrus (pSTS/MTG), while electroencephalography (EEG) studies have shown oscillatory activity in specific frequency bands to be associated with multisensory integration. In the current study, we used fMRI and EEG to separately investigate the anatomical and oscillatory neural signature of integrating intrinsically meaningful gestures (IMG; e.g. “Thumbs-up gesture”) and corresponding speech (e.g., “The actor did a good job”). In both the fMRI (n=20) and EEG (n=20) study, participants were presented with videos of an actor either: performing IMG in the context of a German sentence (GG), IMG in the context of a Russian (as a foreign language) sentence (GR), or speaking an isolated German sentence without gesture (SG). The results of the fMRI experiment confirmed that gesture–speech processing of IMG activates the posterior MTG (GG>GR∩GG>SG). In the EEG experiment we found that the identical integration process (GG>GR∩GG>SG) is related to a centrally-distributed alpha (7–13 Hz) power decrease within 700–1400 ms post-onset of the critical word. These new findings suggest that BOLD response increase in the pMTG and alpha power decrease represent the neural correlates of integrating intrinsically meaningful gestures with their corresponding speech.

Genetic studies found the A allele of the single nucleotide polymorphism rs1006737 in the CACNA1C gene, which encodes for the alpha 1C subunit of the voltage-dependent, L-type calcium ion channel Cav1.2, to be overrepresented in patients with major depressive disorder (MDD). Altered prefrontal brain functioning and impaired semantic verbal fluency (SVF) are robust findings in these patients. A recent functional magnetic resonance imaging (fMRI) study found the A allele to be associated with poorer performance and increased left inferior frontal gyrus (IFG) activation during SVF tasks in healthy subjects. In the present study, we investigated the effects of rs1006737 on neural processing during SVF in MDD. In response to semantic category cues, 40 patients with MDD and 40 matched controls overtly generated words while brain activity was measured with fMRI. As revealed by whole brain analyses, genotype significantly affected brain activity in patients. Compared to patients with GG genotype, patients with A allele demonstrated increased task-related activation in the left middle/inferior frontal gyrus and the bilateral cerebellum. Patients with A allele also showed enhanced functional coupling between left middle/inferior and right superior/middle frontal gyri. No differential effects of genotype on SVF performance or brain activation were found between diagnostic groups. The current data provide further evidence for an impact of rs1006737 on the left IFG and demonstrate that genetic variation in CACNA1C modulates neural responses in patients with MDD. The observed functional alterations in prefrontal and cerebellar areas might represent a mechanism by which rs1006737 influences susceptibility to MDD.

Human language allows us to express our thoughts and ideas by combining entities, concepts and actions into multi-event episodes. Yet, the functional neuroanatomy engaged in interpretation of such high-level linguistic input remains poorly understood. Here, we used easy to detect and more subtle "borderline" anomalies to investigate the brain regions and mechanistic principles involved in the use of real-world event knowledge in language comprehension. Overall, the results showed that the processing of sentences in context engages a complex set of bilateral brain regions in the frontal, temporal and inferior parietal lobes. Easy anomalies preferentially engaged lower-order cortical areas adjacent to the primary auditory cortex. In addition, the left supramarginal gyrus and anterior temporal sulcus as well as the right posterior middle temporal gyrus contributed to the processing of easy and borderline anomalies. The observed pattern of results is explained in terms of (i) hierarchical processing along a dorsal-ventral axis and (ii) the assumption of high-order association areas serving as cortical hubs in the convergence of information in a distributed network. Finally, the observed modulation of BOLD signal in prefrontal areas provides support for their role in the implementation of executive control processes. Refereed/Peer-reviewed

The neural correlates of theory of mind (ToM) are typically studied using paradigms which require participants to draw explicit, task‐related inferences (e.g., in the false belief task). In a natural setup, such as listening to stories, false belief mentalizing occurs incidentally as part of narrative processing. In our experiment, participants listened to auditorily presented stories with false belief passages (implicit false belief processing) and immediately after each story answered comprehension questions (explicit false belief processing), while neural responses were measured with functional magnetic resonance imaging (fMRI). All stories included (among other situations) one false belief condition and one closely matched control condition. For the implicit ToM processing, we modeled the hemodynamic response during the false belief passages in the story and compared it to the hemodynamic response during the closely matched control passages. For implicit mentalizing, we found activation in typical ToM processing regions, that is the angular gyrus (AG), superior medial frontal gyrus (SmFG), precuneus (PCUN), middle temporal gyrus (MTG) as well as in the inferior frontal gyrus (IFG) billaterally. For explicit ToM, we only found AG activation. The conjunction analysis highlighted the left AG and MTG as well as the bilateral IFG as overlapping ToM processing regions for both implicit and explicit modes. Implicit ToM processing during listening to false belief passages, recruits the left SmFG and billateral PCUN in addition to the “mentalizing network” known form explicit processing tasks. Hum Brain Mapp 36:4231–4246, 2015. © 2015 Wiley Periodicals, Inc.

The correlation of formal thought disorder (FTD) symptoms and subsyndromes with neuropsychological dimensions is as yet unclear. Evidence for a dysexecutive syndrome and semantic access impairments has been discussed in positive FTD, albeit focusing mostly on patients with schizophrenia. We investigated the correlation of the full range of positive and negative as well as subjective and objective FTD with neuropsychological domains in different patient groups. Patients with ICD-10 schizophrenia (n = 51), depression (n = 51), and bipolar mania (n = 18), as well as healthy subjects (n = 60), were interviewed with the Rating Scale for the Assessment of Objective and Subjective Formal Thought and Language Disorder (TALD) and assessed using a multidimensional neuropsychological test battery (executive function, semantic and lexical verbal fluency, attention, working memory, and abstract thinking). Partial correlation analysis, controlling for age and word knowledge, revealed significant results for the objective positive FTD dimension and executive dysfunctions. Objective negative FTD was associated with deficits in lexico-semantic retrieval, as well as attention and working memory dysfunctions. The results suggest that different neuropsychological substrates correlate with the multidimensional and phenomenologically different FTD syndromes. FTD is a complex, multidimensional syndrome with a variety of neuropsychological impairments, which should be accounted for in future studies investigating the pathogenesis of FTD.

Formal thought disorder (FTD) is a core syndrome of schizophrenia. However, patients with other diagnoses, such as mania and depression amongst others, also present with FTD. We introduce a novel, comprehensive clinical rating scale, capturing the full variety of FTD phenomenology including subjective experiences. The 30-item Thought and Language Disorder (TALD) scale is based on a detailed review of the literature, encompassing all formal thought disorder symptoms reported from the early 20th century onwards. Objectively observable symptoms as well as subjective phenomena were included. Two hundred and ten participants (146 patients ICD-10 diagnoses: depression n. = 63, schizophrenia n. = 63, mania n. = 20; 64 healthy control subjects) were interviewed and symptoms rated with the TALD, TLC, HAMD, YMRS and SAPS/SANS. A principal component analyses was performed for the TALD to differentiate sub-syndromes. The principal component analysis revealed four FTD factors; objective and subjective as well as positive and negative factor dimensions. The correlation analyses with the TLC and the SAPS/SANS FTD sub-scores demonstrated the factor validity for the objective factors. The different diagnoses showed a distinct pattern of symptom severity in each of the factors, with mania patients exhibiting the highest value in the positive, objective dimension. The scale showed good psychometric results, which makes it a practicable, nosologically-open instrument for the detailed assessment of all FTD dimensions. The results strengthen the importance of subjective symptom assessment reported by the patient. DFG (project no. Ki 588/6-1) Scopus

During face‐to‐face communication, body orientation and coverbal gestures influence how information is conveyed. The neural pathways underpinning the comprehension of such nonverbal social cues in everyday interaction are to some part still unknown. During fMRI data acquisition, 37 participants were presented with video clips showing an actor speaking short sentences. The actor produced speech‐associated iconic gestures (IC) or no gestures (NG) while he was visible either from an egocentric (ego) or from an allocentric (allo) position. Participants were asked to indicate via button press whether they felt addressed or not. We found a significant interaction of body orientation and gesture in addressment evaluations, indicating that participants evaluated IC‐ego conditions as most addressing. The anterior cingulate cortex (ACC) and left fusiform gyrus were stronger activated for egocentric versus allocentric actor position in gesture context. Activation increase in the ACC for IC‐ego>IC‐allo further correlated positively with increased addressment ratings in the egocentric gesture condition. Gesture‐related activation increase in the supplementary motor area, left inferior frontal gyrus and right insula correlated positively with gesture‐related increase of addressment evaluations in the egocentric context. Results indicate that gesture use and body‐orientation contribute to the feeling of being addressed and together influence neural processing in brain regions involved in motor simulation, empathy and mentalizing. Hum Brain Mapp 36:1925–1936, 2015. © 2015 Wiley Periodicals, Inc.

Patients with schizophrenia (SZ) often make aberrant cause and effect inferences in non-social and social situations. Likewise, patients may perceive cause-and-effect relationships abnormally as a result of an alteration in the physiology of perception. The neural basis for dysfunctions in causality judgements in the context of both physical motion and social motion is unknown. The current study used functional magnetic resonance imaging (fMRI) to investigate a group of patients with SZ and a group of control subjects performing judgements of causality on animated collision sequences (launch-events, Michotte, 1963 ) and comparable “social” motion stimuli. In both types of animations, similar motion trajectories of the affected object were configured, using parametrical variations of space (angle deviation) and time (delay). At the behavioural level, SZ patients made more physical and less social causal judgements than control subjects, and their judgements were less influenced by motion attributes (angle/time delay). In the patients group, fMRI revealed greater BOLD-responses, during both physical and social causality judgements (group × task interaction), in the left inferior frontal gyrus (L.IFG). Across conditions (main effect), L.IFG-interconnectivity with bilateral occipital cortex was reduced in the patient group. This study provides the first insight into the neural correlates of altered causal judgements in SZ. Patients with SZ tended to over-estimate physical and under-estimate social causality. In both physical and social contexts, patients are influenced less by motion parameters (space and time) than control subjects. Imaging findings of L.IFG-disconnectivity and task-related hyper-activation in the patient group could indicate common dysfunctions in the neural activations needed to integrate external cue-information (space/time) with explicit (top–down) cause–effect judgements of object motions in physical and social settings.

Major depression is associated with impairments in semantic verbal fluency (VF). However, the neural correlates underlying dysfunctional cognitive processing in depressed subjects during the production of semantic category members still remain unclear. In the current study, an overt and continuous semantic VF paradigm was used to examine these mechanisms in a representative sample of 33 patients diagnosed with a current episode of unipolar depression and 33 statistically matched healthy controls. Subjects articulated words in response to semantic category cues while brain activity was measured with functional magnetic resonance imaging (fMRI). Compared to controls, patients showed poorer task performance. On the neural level, a group by condition interaction analysis, corrected for task performance, revealed a reduced task-related deactivation in patients in the right parahippocampal gyrus, the right fusiform gyrus, and the right supplementary motor area. An additional and an increased task-related activation in patients were observed in the right precentral gyrus and the left cerebellum, respectively. These results indicate that a failure to suppress potentially interfering activity from inferior temporal regions involved in default-mode network functions and visual imagery, accompanied by an enhanced recruitment of areas implicated in speech initiation and higher-order language processes, may underlie dysfunctional cognitive processing during semantic VF in depression. The finding that patients with depression demonstrated both decreased performance and aberrant brain activation during the current semantic VF task demonstrates that this paradigm is a sensitive tool for assessing brain dysfunctions in clinical populations.

Previous positron emission tomography (PET) studies employing competition paradigms have shown either no change or substantial declines in striatal ( 11 C)-raclopride binding after challenge with psychotogenic doses of the N-methyl-D-aspartate antagonist ketamine. We sought to probe the relationship between the severity of ketamine-induced psychotic symptoms and altered dopamine D2/3 receptor availability throughout brain using the high affinity ligand ( 18 F)-fallypride (FP). PET recordings were obtained in a group of 10 healthy, young male volunteers, in a placebo condition, and in the course of an infusion with ketamine at a psychotomimetic dose. Administration of the Positive and Negative Syndrome Scale and the Thought and Language Index in both conditions revealed a substantial emergence of mainly negative symptoms of schizophrenia, persisting until the end of the 3 h PET recordings. The baseline FP binding in cortex, caudate nucleus and other brain regions was highly predictive of the individual severity of psychotic symptoms in the ketamine condition. However, there was no evidence of ketamine-evoked reductions in FP binding. In the context of earlier findings, we speculate that high baseline D2/3-receptor availability may impart benefits with regard to cognitive flexibility, but increases the risk of maladaptive information processing in the face of environmental stresses and challenges. 18 F)fallypride, ketamine, positron emission tomography, psychosis, thought disorder, vulnerability.

Understanding cause and effect is a fundamental aspect of human cognition. When shown videos of simple two-dimensional shapes colliding, humans experience one object causing the other to move, e.g., one billiard-like ball seeming to hit and move the other. The impression of causality can also occur when people attribute social interactions to moving objects. Whether the judgment of social and physical causality engages distinct or shared neural networks is not known. In a functional magnetic imaging (fMRI) study, participants were presented with two types of dynamic videos: a blue ball colliding with a red ball (P; physical condition) and a blue ball (“Mr. Blue”) passing a red ball (“Mrs. Red”) without making contact (S; social condition). Participants judged causal relationships (C) or movement direction (D; control task) in both video types, resulting in four conditions (PC; SC; PD; SD). We found common neural activations for physical and social causality judgments (SC>SD)∩(PC>PD) in the right middle/inferior frontal gyrus, right inferior parietal lobule, the right supplementary motor area, and bilateral insulae. For social causal judgments (SC>PC), we found distinct neural activity in the right temporo-parietal junction (rTPJ). These results provide evidence for a common neural network underlying judgments of causality that apply to both physical and social situations. The results also indicate that social causality judgments recruit additional neural resources in an area critical for determining animacy and intentionality.

The Scale for the Assessment of Thought, Language and Communication (TLC) represents an instrument for the assessment of formal thought disorder (FTD). The factorial dimensionality of the TLC has yielded ambiguous results for a distinction between positive (e.g. circumstantiality) and negative (e.g. poverty of speech) FTD. The purpose of the current study was to first translate and validate the TLC scale in German. Second, the internal structure was explored in order to identify different FTD dimensions. Two hundred and ten participants (146 patients with ICD-10 diagnoses: depression n = 63, schizophrenia n = 63, mania n = 20; 64 healthy subjects) were interviewed and FTD was rated with the TLC. The principal component analysis of the German TLC version revealed a 3-factor solution, reflecting a disorganized factor, an emptiness factor and a linguistic control factor. The current investigation yielded similar results to those originally reported for the TLC. Thus, a distinction between a positive disorganized, a negative and a semantic word level factor can be supported for the German translation.

Causality provides a natural structure for organizing our experience and language. Causal reasoning during speech production is a distinct aspect of verbal communication, whose related brain processes are yet unknown. The aim of the current study was to investigate the neural mechanisms underlying the continuous generation of cause-and-effect coherences during overt word production. During fMRI data acquisition participants performed three verbal fluency tasks on identical cue words: A novel causal verbal fluency task (CVF), requiring the production of multiple reasons to a given cue word (e.g. reasons for heat are fire, sun etc.), a semantic (free association, FA, e.g. associations with heat are sweat, shower etc.) and a phonological control task (phonological verbal fluency, PVF, e.g. rhymes with heat are meat, wheat etc.). We found that, in contrast to PVF, both CVF and FA activated a left lateralized network encompassing inferior frontal, inferior parietal and angular regions, with further bilateral activation in middle and inferior as well as superior temporal gyri and the cerebellum. For CVF contrasted against FA, we found greater bold responses only in the left middle frontal cortex. Large overlaps in the neural activations during free association and causal verbal fluency indicate that the access to causal relationships between verbal concepts is at least partly based on the semantic neural network. The selective activation in the left middle frontal cortex for causal verbal fluency suggests that distinct neural processes related to cause-and-effect-relations are associated with the recruitment of middle frontal brain areas.

Typically, plural nouns are morphosyntactically marked for the number feature, whereas mass nouns are morphosyntactically singular. However, both plural count nouns and mass nouns can be semantically interpreted as nonsingular. In this study, we investigated the hypothesis that their commonality in semantic interpretation may lead to common cortical activation for these different kinds of nonsingularity. To this end, we examined brain activation patterns related to three types of nouns while participants were listening to a narrative. Processing of plural compared with singular nouns was related to increased activation in the left angular gyrus. Processing of mass nouns compared with singular count nouns was related to increased activity bilaterally in the superior temporal cortex and also in the left angular gyrus. No significant activation was observed in the direct comparison between plural and mass nouns. We conclude that the left angular gyrus, also known to be relevant for numerical cognition, is involved in the semantic interpretation of different kinds of nonsingularity.

The N-methyl-d-aspartate receptor (NMDAR) has been implicated in the pathophysiology of schizophrenia. Administered to healthy individuals, a subanesthetic dose of the noncompetitive NMDAR antagonist ketamine reproduces several psychopathological symptoms commonly observed in patients with schizophrenia. In a counterbalanced, placebo-controlled, double-blind, within-participants study, fifteen healthy subjects were administered a continuous subanesthetic S-ketamine infusion while cortical activation was measured using functional magnetic resonance imaging. While being scanned, subjects performed an overt word generation task. Ketamine-induced psychopathological symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS). Ketamine administration elicited effects on psychopathology, including difficulties in abstract thinking, lack of spontaneity and flow of conversation as well as formal thought disorder. On a behavioral level, verbal fluency performance was unaffected. The PANSS score for formal thought disorder positively correlated with activation measures encompassing the left superior temporal gyrus, the right middle and inferior frontal gyrus and the precuneus. Difficulty in abstract thinking was correlated with pronounced activations in prefrontal as well as in anterior cingulate regions, whereas hyperactivations in the left superior temporal gyrus were found in association with a lack of spontaneity and flow of conversation. In the absence of behavioral impairments during verbal fluency, NMDAR blocking evoked psychopathological symptoms and cortical activations in regions previously reported in schizophrenia patients. The results provide further support for the hypothesis of an NMDAR dysfunction in the pathophysiology of schizophrenia.

Rhyming words, as in songs or poems, is a universal feature of human language across all ages. In the present fMRI study a novel overt rhyming task was applied to determine the neural correlates of rhyme production. Fifteen right-handed healthy male volunteers participated in this verbal fluency study. Participants were instructed to overtly articulate as many words as possible either to a given initial letter (LVF) or to a semantic category (SVF). During the rhyming verbal fluency task (RVF), participants had to generate words that rhymed with pseudoword stimuli. On-line overt verbal responses were audiotaped in order to correct the imaging results for the number of generated words. Fewer words were generated in the rhyming compared to both the lexical and the semantic condition. On a neural level, all language tasks activated a language network encompassing the left inferior frontal gyrus, the middle and superior temporal gyri as well as the contralateral right cerebellum. Rhyming verbal fluency compared to both lexical and semantic verbal fluency demonstrated significantly stronger activation of left inferior parietal region. Generating novel rhyme words seems to be mainly mediated by the left inferior parietal lobe, a region previously found to be associated with meta-phonological as well as sub-lexical linguistic processes.