Arne Nagels

Is formal thought disorder in schizophrenia related to structural and functional aberrations in the language network? A systematic review of neuroimaging findings

Formal thought disorder (FTD) is a core feature of schizophrenia, a marker of illness severity and a predictor of outcome. The underlying neural mechanisms are still a matter of debate. This study aimed at 1) reviewing the literature on the neural correlates of FTD in schizophrenia, and 2) testing the hypothesis that FTD correlates with structural and functional aberrations in the language network. Medline, PsychInfo, and Embase were searched for neuroimaging studies, which applied a clinical measure to assess FTD in adults with schizophrenia and were published in English or German in peer-reviewed journals until December 2016. Of 412 articles identified, 61 studies were included in the review. Volumetric studies reported bilateral grey matter deficits (Lu202f>u202fR) to be associated with FTD in the inferior frontal gyrus, the superior temporal gyrus and the inferior parietal lobe. The same regions showed hyperactivity in resting state functional magnetic resonance imaging (fMRI) studies and both hyper- and hypoactivity in fMRI studies that employed semantic processing or free speech production tasks. Diffusion tensor imaging studies demonstrated white matter aberrations in fibre tracts that connect the frontal and temporo-parietal regions. FTD in schizophrenia was found to be associated with structural and functional aberrations in the language network. However, there are studies that did not find an association between FTD and neural aberrations of the language network and regions not included in the language network have been associated with FTD. Thus, future research is needed to clarify the specificity of the language network for FTD in schizophrenia.

Spatial–temporal dynamics of gesture–speech integration: a simultaneous EEG-fMRI study

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 (nu2009=u200919) 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 GGu2009>u2009GRu2009∩u2009GGu2009>u2009SG. 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.

The role of the right temporo-parietal junction in social decision-making

Identifying someone elses noncooperative intentions can prevent exploitation in social interactions. Hence, the inference of another persons 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 prisoners 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.

Symptoms and Neurobiological Models of Language in Schizophrenia

Patients with schizophrenia suffer from impairments on all levels of speech and language, ranging from the most simple auditory perceptual to complex pragmatic processing, including production deficits. Electrophysiological, structural, and functional brain imaging as well as postmortem research established dysconnectivity within and between lateral fronto-temporal areas and their trans-callosal connections as a likely cause for these language-related impairments. Cortical thinning found particularly in the lateral temporal regions in patients is likely due to synaptic rarefication. The glutamatergic and dopamine neurotransmitter systems are predominantly involved in psychopathological symptom formation. Thus, no isolated focal impairment in one brain region is associated with the complex language aberrations in schizophrenia, but rather disruptions in the dynamic interplay between and within neural circuits on multiple levels, which further change over time (minutes to years), paralleling symptom fluctuation and the long-term individual course of illness. Future studies may apply joint phenomenological, physiological, pharmacological, and longitudinal (epi-)genetic/environment approaches to further elucidate the pathomechanisms of language impairments in schizophrenia.

Frontal hypoactivation and alterations in the reward-system during humor processing in patients with schizophrenia spectrum disorders

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.

Impaired Right Temporoparietal Junction–Hippocampus Connectivity in Schizophrenia and Its Relevance for Generating Representations of Other Minds

Schizophrenia is associated with impaired and exaggerated Theory of Mind processes, pointing on alterations in generating a representation of another persons 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 prisoners 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.

Hand Gestures Alert Auditory Cortices

When acquiring a foreign language, the first challenge is to break into the speech stream to identify basic linguistic units. The present study tested the hypothesis that hand gestures facilitate this process by alerting auditory cortices to attend to and identify meaningful phonemic information. During fMRI data acquisition, participants watched videos of an actor speaking in Russian under three conditions. Sentences were produced with just speech alone or were accompanied by two types of hand gestures: 1) metaphoric gesture and 2) free gesture. The main finding was that there was increased auditory cortex activation when both types of gestures accompanied speech compared to speech alone, but there were no differences between the two speech + gesture conditions (or gesture alone conditions). These results suggest that hand gestures may play a role in focusing attention to auditory processing to increase capacity when listening to novel speech in a foreign language.

The Role of Gamma Oscillations During Integration of Metaphoric Gestures and Abstract Speech

Metaphoric (MP) co-speech gestures are commonly used during daily communication. They communicate about abstract information by referring to gestures that are clearly concrete (e.g., raising a hand for “the level of the football game is high”). To understand MP co-speech gestures, a multisensory integration at semantic level is necessary between abstract speech and concrete gestures. While semantic gesture-speech integration has been extensively investigated using functional magnetic resonance imaging, evidence from electroencephalography (EEG) is rare. In the current study, we set out an EEG experiment, investigating the processing of MP vs. iconic (IC) co-speech gestures in different contexts, to reveal the oscillatory signature of MP gesture integration. German participants (n = 20) viewed video clips with an actor performing both types of gestures, accompanied by either comprehensible German or incomprehensible Russian (R) speech, or speaking German sentences without any gestures. Time-frequency analysis of the EEG data showed that, when gestures were accompanied by comprehensible German speech, MP gestures elicited decreased gamma band power (50–70 Hz) between 500 and 700 ms in the parietal electrodes when compared to IC gestures, and the source of this effect was localized to the right middle temporal gyrus. This difference is likely to reflect integration processes, as it was reduced in the R language and no-gesture conditions. Our findings provide the first empirical evidence suggesting the functional relationship between gamma band oscillations and higher-level semantic processes in a multisensory setting.

Action-Related Speech Modulates Beta Oscillations During Observation of Tool-Use Gestures

Language and action have been thought of as closely related. Comprehending words or phrases that are related to actions commonly activates motor and premotor areas, and this comprehension process interacts with action preparation and/or execution. However, it remains unclear whether comprehending action-related language interacts with action observation. In the current study, we examined whether the observation of tool-use gesture subjects to interaction with language. In an electroencephalography (EEG) study (nu2009=u200920), participants were presented with video clips of an actor performing tool-use (TU, e.g., hammering with a fist) and emblematic (EM, e.g., the thumb up sign for ‘good job’) gestures accompanied by either comprehensible German (G) or incomprehensible Russian sentences (R). Participants performed a semantic judging task, evaluating whether the co-speech gestures were object- or socially-related. Behavioral results from the semantic task showed faster response for the TU versus EM gestures only in the German condition. For EEG, we found that TU elicited beta power decrease (~u200920xa0Hz) when compared to EM gestures, however this effect was reduced when gestures were accompanied by German instead of Russian sentences. We concluded that the processing of action-related sentences might facilitate gesture observation, in the sense that motor simulation required for TU gestures, as indexed by reduced beta power, was modulated when accompanied by comprehensible German speech. Our results corroborate the functional role of the beta oscillations during perception of hand gestures, and provide novel evidence concerning language–motor interaction.