Neural activation during natural speech and rests in patients with schizophrenia and schizophrenia spectrum disorders-an fMRI pilot trial.

Background: In schizophrenia patients, spontaneous speech production has been hypothesized as correlating with right hemispheric activation, including the inferior frontal and superior temporal gyri as speech-relevant areas. However, robust evidence for this association is still missing. The aim of the present fMRI study is to examine BOLD signal changes during natural, fluent speech production in patients with schizophrenia in the chronic phase of their disease. Methods: Using a case-control design, the study included 15 right-handed patients with schizophrenia spectrum disorders as well as 15 healthy controls. The participants described eight pictures from the Thematic Apperception Test for 1 min each, while BOLD signal changes were measured with 3T fMRI. The occurrence of positive and negative formal thought disorders was determined using standardized psychopathological assessments. Results: We found significant BOLD signal changes during spontaneous speech production in schizophrenia patients compared to healthy controls, particularly in the right hemispheric network. A post-hoc analysis showed that this right-hemispheric lateralization was mainly driven by activation during experimental rests. Furthermore, the TLI sum value in patients correlated negatively with BOLD signal changes in the right Rolandic operculum. Conclusions: Possible underlying factors for this inverse right-hemispheric lateralization of speech-associated areas are structural changes and transmitter system alterations, as well as a lack of neural downregulation in schizophrenia patients during rest periods due to dysfunctional executive functions. When examining spontaneous speech as the most natural form of language, other influencing factors, such as social cognition or emotional processing, should be considered. Our results indicate that future studies should consider group differences during rest, which might provide additional information typically covered in differential contrasts.

Multivariate pattern analysis of EEG reveals nuanced impact of negation on sentence processing in the N400 and later time windows.

The neurocognitive mechanism underlying negation processing remains controversial. While negation is suggested to modulate the access of word meaning, no such evidence has been observed in the event-related potential (ERP) literature on sentence processing. In the current study, we applied both univariate ERP and multivariate pattern analysis (MVPA) methods to examine the processing of sentence negation. We investigated two types of negative congruent/incongruent sentence pairs with truth-value evaluation (e.g., "A robin is a/not a bird") and without (e.g., "The woman reads a/no book"). In the N400 time window, ERPs consistently showed increased negativity for negative and incongruent conditions. MVPA, on the other hand, revealed nuanced interactions between polarity and congruency. In the later P600 time window, MVPA but not the ERPs revealed an effect of congruency, which may be functionally distinct from the N400 window. We further used cross-decoding to show that the cognitive processes underlying the N400 window for both affirmative and negative sentences are comparable, whereas in the P600 window, only for the truth sentences, negative sentences showed a distinct pattern from their affirmative counterparts. Our results thus speak for a more interactive, but nevertheless serial and biphasic, and potentially construction-specific processing account of negation. We also discuss the advantage of applying MVPA in addition to the classical univariate methods for a better understanding of the neurobiology of negation processing and language comprehension alike.

Syntactic complexity and diversity of spontaneous speech production in schizophrenia spectrum and major depressive disorders.

Syntax, the grammatical structure of sentences, is a fundamental aspect of language. It remains debated whether reduced syntactic complexity is unique to schizophrenia spectrum disorder (SSD) or whether it is also present in major depressive disorder (MDD). Furthermore, the association of syntax (including syntactic complexity and diversity) with language-related neuropsychology and psychopathological symptoms across disorders remains unclear. Thirty-four SSD patients and thirty-eight MDD patients diagnosed according to DSM-IV-TR as well as forty healthy controls (HC) were included and tasked with describing four pictures from the Thematic Apperception Test. We analyzed the produced speech regarding its syntax delineating measures for syntactic complexity (the total number of main clauses embedding subordinate clauses) and diversity (number of different types of complex sentences). We performed cluster analysis to identify clusters based on syntax and investigated associations of syntactic, to language-related neuropsychological (verbal fluency and verbal episodic memory), and psychopathological measures (positive and negative formal thought disorder) using network analyses. Syntax in SSD was significantly reduced in comparison to MDD and HC, whereas the comparison of HC and MDD revealed no significant differences. No associations were present between speech measures and current medication, duration and severity of illness, age or sex; the single association accounted for was education. A cluster analysis resulted in four clusters with different degrees of syntax across diagnoses. Subjects with less syntax exhibited pronounced positive and negative symptoms and displayed poorer performance in executive functioning, global functioning, and verbal episodic memory. All cluster-based networks indicated varying degrees of domain-specific and cross-domain connections. Measures of syntactic complexity were closely related while syntactic diversity appeared to be a separate node outside of the syntactic network. Cross-domain associations were more salient in more complex syntactic production.

State of illness-dependent associations of neuro-cognition and psychopathological syndromes in a large transdiagnostic cohort.

BACKGROUND: There is a lack of knowledge regarding the relationship between dimensional psychopathological syndromes and neurocognitive functions, particularly across the major psychiatric disorders (i.e., Major Depressive Disorder (MDD), Bipolar Disorder (BD), and Schizophrenia (SZ)). METHOD: SANS, SAPS, HAMA, HAM-D, and YMRS were assessed in 1064 patients meeting DSM-IV-TR criteria for MDD, BD, SZ or schizoaffective disorder (SZA). In addition, a comprehensive neuropsychological test battery was administered. Psychopathological syndromes derived from factor analysis and present state of illness were used to explore psychopathology-cognition relationships. Correlational analyses were corrected for age, sex, verbal IQ, years of education, and DSM-IV-TR diagnosis. Age of onset and total duration of hospitalizations as proxies for illness severity were tested as moderators on the cognition - psychopathology relationship. RESULTS: The negative syndrome, positive formal thought disorder as well as the paranoid-hallucinatory syndrome exhibited associations with neuro-cognition in an illness state-dependent manner, while the psychopathological factors depression and increased appetite only showed weak associations. Illness severity showed moderating effects on the neurocognitive-psychopathology relationship only for the negative syndrome and positive formal thought disorder. LIMITATIONS: No healthy control subjects were entered into the analyses because of lack of variance in psychopathological symptoms, which prevents from drawing conclusions regarding the relative level of potential cognitive impairments. CONCLUSIONS: This study suggests the relationship of neuro-cognition and psychopathology to be highly state of illness-dependent across affective and psychotic disorders. Results hint at the moderating effects of illness severity on psychopathological factors that might be more treatment resistant.

Multimodal speech-gesture training in patients with schizophrenia spectrum disorder: Effects on quality of life and neural processing.

Dysfunctional social communication is one of the most stable characteristics in patients with schizophrenia spectrum disorder (SSD) that severely affects quality of life. Interpreting abstract speech and integrating nonverbal information is particularly affected. Considering the difficulty to treat communication dysfunctions with usual intervention, we investigated the possibility to apply a multimodal speech-gesture (MSG) training. In the MSG training, we offered 8 sessions (60 min each) including perceptive and expressive tasks as well as meta-learning elements and transfer exercises to 29 patients with SSD. In a within-group crossover design, patients were randomized to a TAU-first (treatment as usual first, then MSG training) group (N = 20) or a MSG-first (MSG training first, then TAU only) group (N = 9), and were compared to healthy controls (N = 17). Outcomes were quality of life and related changes in the neural processing of abstract speech-gesture information, which were measured pre-post training through standardized psychological questionnaires and functional Magnetic Resonance Imaging, respectively. Pre-training, patients showed reduced quality of life as compared to controls but improved significantly during the training. Strikingly, this improvement was correlated with neural activation changes in the middle temporal gyrus for the processing of abstract multimodal content. Improvement during training, self-report measures and ratings of relatives confirmed the MSG-related changes. Together, we provide first promising results of a novel multimodal speech-gesture training for patients with schizophrenia. We could link training induced changes in speech-gesture processing to changes in quality of life, demonstrating the relevance of intact communication skills and gesture processing for well-being.

Metaphorical expressions originating from human senses: Psycholinguistic and affective norms for German metaphors for internal state terms (MIST database).

Internal states, e.g., emotions, cognitive states, or desires, are often verbalized by figurative means, in particular by embodied metaphors involving human senses, such as touch, taste, and smell. The present paper presents a database for German metaphorical expressions conveying internal states with human senses as their source domains. 168 metaphorical expressions from the source domains of vision, hearing, smell, taste, touch, and temperature combined with literal equivalents were collected and rated by 643 adults. The agreement between the metaphor and an equivalent literal expression, as well as emotional valence, arousal, and familiarity values were assessed using a 7-point Likert scale. Between the metaphorical expressions and their equivalents, familiarity, but not valence or arousal differed significantly while agreement ratings indicated high similarity in meaning. The novel database offers carefully controlled stimuli that can be used in both empirical metaphor research and research on internal state language. Using part of the stimuli in a sentence completion experiment revealed a significant preference for literal over metaphorical expressions that cannot be attributed to higher familiarity levels.

Differences in single positive formal thought disorder symptoms between closely matched acute patients with schizophrenia and mania.

Formal thought disorders (FTD) are a hallmark diagnostic feature of schizophrenia (SZ) and (bipolar) mania (MA). FTD can be separated into positive (pFTD) and negative dimensions. It is unclear whether there are differences in pFTD on a single symptom level between acutely ill patients with SZ and MA, which cannot be attributed to cognitive impairment. We compared single pFTD symptoms in two groups of acutely ill patients with ICD-10 bipolar mania and schizophrenia, closely matched for age, sex, pFTD TALD score, verbal IQ and neuropsychological test performance (executive function, verbal fluency, attention, and working memory). SZ patients had higher severity of the TALD symptoms "perseverations" and "poverty of content of speech" than those with MA (Mann-Whitney U, significant, Bonferroni corrected). Speech in acute SZ patients differs from MA in that it conveys little information and adheres to previously mentioned ideas and topics. Matching for confounding variables, such as IQ and cognition, is important when comparing patients with different diagnoses.

Neural processing of nouns and verbs in spontaneous speech of patients with schizophrenia.

Previous fMRI-studies investigating the production of nouns and verbs in healthy participants reported predominantly activation in the left inferior frontal gyrus (IFG) for both classes of words with increased neural responses for verbs. To date, comparable imaging data for spontaneous speech in patients with schizophrenia is missing. These results are novel and may contribute to understand the neural basis of noun and verb production in a "natural" environment. Fifteen patients with schizophrenia and fifteen healthy control participants described pictures for one minute each while BOLD signal changes were measured with fMRI. In an event-related design, activations related to noun and verb production were extracted in the imaging analysis. Imaging results revealed increased activation for nouns and decreased activation for verbs in the left IFG in the patients. A post-hoc analysis revealed that patients produced significantly more transitive verbs which were negatively associated with activation in the left IFG. We conclude that a subtle linguistic processing deficit in schizophrenia may lead to an increased use of transitive as compared to intransitive verbs in connected speech and to a deviant pattern of brain activation related to the processing of verbs.

Neural Basis of Speech-Gesture Mismatch Detection in Schizophrenia Spectrum Disorders.

Patients with schizophrenia spectrum disorders (SSD) exhibit an aberrant perception and comprehension of abstract speech-gesture combinations associated with dysfunctional activation of the left inferior frontal gyrus (IFG). Recently, a significant deficit of speech-gesture mismatch detection was identified in SSD, but the underlying neural mechanisms have not yet been examined. A novel mismatch-detection fMRI paradigm was implemented manipulating speech-gesture abstractness (abstract/concrete) and relatedness (related/unrelated). During fMRI data acquisition, 42 SSD patients (schizophrenia, schizoaffective disorder, or other non-organic psychotic disorder [ICD-10: F20, F25, F28; DSM-IV: 295.X]) and 36 healthy controls were presented with short video clips of an actor reciting abstract or concrete sentences accompanied by either a semantically related or unrelated gesture. Participants indicated via button press whether they perceived each gesture as matching the speech content or not. Speech-gesture mismatch detection performance was significantly impaired in patients compared to controls. fMRI data analysis revealed that patients showed lower activation in bilateral frontal areas, including the IFG for all abstract > concrete speech-gesture pairs. In addition, they exhibited reduced engagement of the right supplementary motor area (SMA) and bilateral anterior cingulate cortices (ACC) for unrelated > related stimuli. We provide first evidence that impaired speech-gesture mismatch detection in SSD could be the result of dysfunctional activation of the SMA and ACC. Failure to activate the left IFG disrupts the integration of abstract speech-gesture combinations in particular. Future investigations should focus on brain stimulation of the SMA, ACC, and the IFG to improve communication and social functioning in SSD.

Antagonism between brain regions relevant for cognitive control and emotional memory facilitates the generation of humorous ideas.

The ability to generate humor gives rise to positive emotions and thus facilitate the successful resolution of adversity. Although there is consensus that inhibitory processes might be related to broaden the way of thinking, the neural underpinnings of these mechanisms are largely unknown. Here, we use functional Magnetic Resonance Imaging, a humorous alternative uses task and a stroop task, to investigate the brain mechanisms underlying the emergence of humorous ideas in 24 subjects. Neuroimaging results indicate that greater cognitive control abilities are associated with increased activation in the amygdala, the hippocampus and the superior and medial frontal gyrus during the generation of humorous ideas. Examining the neural mechanisms more closely shows that the hypoactivation of frontal brain regions is associated with an hyperactivation in the amygdala and vice versa. This antagonistic connectivity is concurrently linked with an increased number of humorous ideas and enhanced amygdala responses during the task. Our data therefore suggests that a neural antagonism previously related to the emergence and regulation of negative affective responses, is linked with the generation of emotionally positive ideas and may represent an important neural pathway supporting mental health.

The role of the left and right inferior frontal gyrus in processing metaphoric and unrelated co-speech gestures.

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.

Asymmetries in Accessing Vowel Representations Are Driven by Phonological and Acoustic Properties: Neural and Behavioral Evidence From Natural German Minimal Pairs.

In vowel discrimination, commonly found discrimination patterns are directional asymmetries where discrimination is faster (or easier) if differing vowels are presented in a certain sequence compared to the reversed sequence. Different models of speech sound processing try to account for these asymmetries based on either phonetic or phonological properties. In this study, we tested and compared two of those often-discussed models, namely the Featurally Underspecified Lexicon (FUL) model (Lahiri and Reetz, 2002) and the Natural Referent Vowel (NRV) framework (Polka and Bohn, 2011). While most studies presented isolated vowels, we investigated a large stimulus set of German vowels in a more naturalistic setting within minimal pairs. We conducted an mismatch negativity (MMN) study in a passive and a reaction time study in an active oddball paradigm. In both data sets, we found directional asymmetries that can be explained by either phonological or phonetic theories. While behaviorally, the vowel discrimination was based on phonological properties, both tested models failed to explain the found neural patterns comprehensively. Therefore, we additionally examined the influence of a variety of articulatory, acoustical, and lexical factors (e.g., formant structure, intensity, duration, and frequency of occurrence) but also the influence of factors beyond the well-known (perceived loudness of vowels, degree of openness) in depth via multiple regression analyses. The analyses revealed that the perceptual factor of perceived loudness has a greater impact than considered in the literature and should be taken stronger into consideration when analyzing preattentive natural vowel processing.

Modality-specific dysfunctional neural processing of social-abstract and non-social-concrete information in schizophrenia.

Schizophrenia is characterized by marked communication dysfunctions encompassing potential impairments in the processing of social-abstract and non-social-concrete information, especially in everyday situations where multiple modalities are present in the form of speech and gesture. To date, the neurobiological basis of these deficits remains elusive. In a functional magnetic resonance imaging (fMRI) study, 17 patients with schizophrenia or schizoaffective disorder, and 18 matched controls watched videos of an actor speaking, gesturing (unimodal), and both speaking and gesturing (bimodal) about social or non-social events in a naturalistic way. Participants were asked to judge whether each video contains person-related (social) or object-related (non-social) information. When processing social-abstract content, patients showed reduced activation in the medial prefrontal cortex (mPFC) only in the gesture but not in the speech condition. For non-social-concrete content, remarkably, reduced neural activation for patients in the left postcentral gyrus and the right insula was observed only in the speech condition. Moreover, in the bimodal conditions, patients displayed improved task performance and comparable activation to controls in both social and non-social content. To conclude, patients with schizophrenia displayed modality-specific aberrant neural processing of social and non-social information, which is not present for the bimodal conditions. This finding provides novel insights into dysfunctional multimodal communication in schizophrenia, and may have potential therapeutic implications.

Characterizing the theory of mind network in schizophrenia reveals a sparser network structure.

Impaired social functioning is a hallmark of schizophrenia and altered functional integration between distant brain regions are expected to account for signs and symptoms of the disorder. The functional neuroarchitecture of a network relevant for social functioning, the mentalizing network, is however poorly understood. In this study we examined dysfunctions of the mentalizing network in patients with schizophrenia compared to healthy controls via dynamic causal modelling and an interactive social decision-making game. Network characteristics were analyzed on a single subject basis whereas graph theoretic metrics such as in-degree, out-degree and edge-connectivity per network node were compared between the groups. The results point to a sparser network structure in patients with schizophrenia and highlight the dorsomedial prefrontal cortex as a disconnected network hub receiving significantly less input from other brain regions in the network. Further analyses suggest that integrating pathways from the right and the left temporo-parietal junction into the dorsomedial prefrontal cortex were less frequently found in patients with schizophrenia. Brain and behavior analyses further suggest that the connectivity-intactness within the entire network is associated with functional interpersonal behavior during the task. Thus, the neurobiological alterations within the mentalizing network in patients with schizophrenia point to a specific integration deficit between core brain regions underlying the generation of higher-order representations and thereby provide a potential treatment target.

Gesture's body orientation modulates the N400 for visual sentences primed by gestures.

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.

Feeling addressed! The neural processing of social communicative cues in patients with major depression.

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.

A Multimodal Speech-Gesture Training Intervention for Patients With Schizophrenia and Its Neural Underpinnings - the Study Protocol of a Randomized Controlled Pilot Trial.

Dysfunctional social communication is one of the most stable characteristics in patients with schizophrenia that also affects quality of life. Interpreting abstract speech and integrating nonverbal modalities is particularly affected. Considering the impact of communication on social life but failure to treat communication dysfunctions with usual treatment, we will investigate the possibility to improve verbal and non-verbal communication in schizophrenia by applying a multimodal speech-gesture training (MSG training). Here we describe the newly developed MSG training program and the study design for the first clinical investigation. The intervention contains perceptive rating (match/mismatch of sentence and gesture) and memory tasks (n-back tasks), imitation and productive tasks (e.g., SG fluency-similar to verbal fluency where words are accompanied by gesture). In addition, we offer information about gesture as meta-learning element as well as homework for reasons of transfer to everyday life as part of every session. In the MSG training intervention, we offer eight sessions (60 min each) of training. The first pilot study is currently conducted as a single-center, randomized controlled trial of speech-gesture intervention versus wait-list control with a follow-up. Outcomes are measured through pre-post-fMRI and standardized psychological questionnaires comparing two subject groups (30 patients with schizophrenia and 30 healthy controls). Patients and healthy controls are randomized in two intervention groups (with 20 being in the wait-training group and 10 in the training-follow-up group). With our study design we will be able to demonstrate the beneficial effect of the MSG training intervention on behavioral and neural levels. CLINICAL TRIAL REGISTRATION: DRKS.de, identifier DRKS00015118.

Factor analyses of multidimensional symptoms in a large group of patients with major depressive disorder, bipolar disorder, schizoaffective disorder and schizophrenia.

BACKGROUND: There is an ongoing discussion about which neurobiological correlates or symptoms separate the major psychoses (i.e. Major Depressive Disorder MDD, Bipolar Disorder BD, and Schizophrenia SZ). Psychopathological factor analyses within one of these disorders have resulted in models including one to five factors. Factor analyses across the major psychoses using a comprehensive set of psychopathological scales in the same patients are lacking. It is further unclear, whether hierarchical or unitarian models better summarize phenomena. METHOD: Patients (n = 1182) who met DSM-IV criteria for MDD, BD, SZ or schizoaffective disorder were assessed with the SANS, SAPS, HAMA, HAM-D, and YMRS. The sample was split into two and analyzed using explorative and confirmatory factor analyses to extract psychopathological factors independent of diagnosis. RESULTS: In the exploratory analysis of sample 1 (n = 593) we found 5 factors. The confirmatory analysis using sample 2 (n = 589) confirmed the 5-factor model (χ2 = 1287.842, df = 571, p < .0001: CFI = 0.932; RMSEA = 0.033). The 5-factors were depression, negative syndrome, positive formal thought disorder, paranoid-hallucinatory syndrome, and increased appetite. Increased appetite was not related to medication. None of the factors was specific for one diagnosis. Second order factor analysis revealed two higher order factors: negative/affective (I) and positive symptoms (II). CONCLUSION: This is the first study delineating psychopathological factors in a large group of patients across the spectrum of affective and psychotic disorders. In future neurobiological studies, we should consider transdiagnostic syndromes besides the traditional diagnoses.

The facilitative effect of gestures on the neural processing of semantic complexity in a continuous narrative.

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.