Hand gesture performance is impaired in major depressive disorder: A matter of working memory performance?

OBJECTIVE Individuals with depression exhibit numerous interpersonal deficits. As effective use of gestures is critical for social communication, it is possible that depressed individuals' interpersonal deficits may be due to deficits in gesture performance. The present study thus compared gesture performance of depressed patients and controls and examined whether these deficits relate to cognitive and other domains of dysfunction. METHODS Gesture performance was evaluated in 30 depressed patients and 30 controls using the Test of Upper Limb Apraxia (TULIA). Clinical rating scales were assessed to determine if gesture deficits were associated with motor, cognitive or functional outcomes. RESULTS Compared to controls, depressed patients exhibited impaired gesture performance with 2/3 of the patients demonstrating gesture deficits. Within depressed patients, gesture performance was highly correlated with working memory abilities. In contrast, no association between gesture performance and gestural knowledge, psychomotor retardation, depression severity, or frontal dysfunction was observed in patients. LIMITATIONS This is a cross-sectional study and a larger size would have allowed for confident detection of more subtle, but potentially relevant effects. CONCLUSION Gesture performance is impaired in depressed patients, and appears to be related to poor working memory abilities, suggesting a disruption in the retrieval of gestural cues indicative of a distinct clinical phenomenon that might be related to social functioning

Limbic links to paranoia: increased resting-state functional connectivity between amygdala, hippocampus and orbitofrontal cortex in schizophrenia patients with paranoia.

Paranoia is a frequent and highly distressing experience in psychosis. Models of paranoia suggest limbic circuit pathology. Here, we tested whether resting-state functional connectivity (rs-fc) in the limbic circuit was altered in schizophrenia patients with current paranoia. We collected MRI scans in 165 subjects including 89 patients with schizophrenia spectrum disorders (schizophrenia, schizoaffective disorder, brief psychotic disorder, schizophreniform disorder) and 76 healthy controls. Paranoia was assessed using a Positive And Negative Syndrome Scale composite score. We tested rs-fc between bilateral nucleus accumbens, hippocampus, amygdala and orbitofrontal cortex between groups and as a function of paranoia severity. Patients with paranoia had increased connectivity between hippocampus and amygdala compared to patients without paranoia. Likewise, paranoia severity was linked to increased connectivity between hippocampus and amygdala. Furthermore, paranoia was associated with increased connectivity between orbitofrontal and medial prefrontal cortex. In addition, patients with paranoia had increased functional connectivity within the frontal hubs of the default mode network compared to healthy controls. These results demonstrate that current paranoia is linked to aberrant connectivity within the core limbic circuit and prefrontal cortex reflecting amplified threat processing and impaired emotion regulation. Future studies will need to explore the association between limbic hyperactivity, paranoid ideation and perceived stress

The cortical signature of impaired gesturing: Findings from schizophrenia

Schizophrenia is characterized by deficits in gesturing that is important for nonverbal communication. Research in healthy participants and brain-damaged patients revealed a left-lateralized fronto-parieto-temporal network underlying gesture performance. First evidence from structural imaging studies in schizophrenia corroborates these results. However, as of yet, it is unclear if cortical thickness abnormalities contribute to impairments in gesture performance. We hypothesized that patients with deficits in gesture production show cortical thinning in 12 regions of interest (ROIs) of a gesture network relevant for gesture performance and recognition. Forty patients with schizophrenia and 41 healthy controls performed hand and finger gestures as either imitation or pantomime. Group differences in cortical thickness between patients with deficits, patients without deficits, and controls were explored using a multivariate analysis of covariance. In addition, the relationship between gesture recognition and cortical thickness was investigated. Patients with deficits in gesture production had reduced cortical thickness in eight ROIs, including the pars opercularis of the inferior frontal gyrus, the superior and inferior parietal lobes, and the superior and middle temporal gyri. Gesture recognition correlated with cortical thickness in fewer, but mainly the same, ROIs within the patient sample. In conclusion, our results show that impaired gesture production and recognition in schizophrenia is associated with cortical thinning in distinct areas of the gesture network

T177. STRUCTURAL ORGANIZATION OF THE PRAXIS NETWORK PREDICTS GESTURE PRODUCTION: EVIDENCE FROM HEALTHY SUBJECTS AND PATIENTS WITH SCHIZOPHRENIA

Abstract Background: Hand gestures are an integral part of social interactions and are involved in nonverbal and verbal communication. The convey language that is expressed by motor actions, and thus depend on the interplay of various brain regions. Several functional magnetic resonance imaging studies in healthy subjects suggest the praxis network for gesture production, involving distinct frontal, parietal and temporal regions. Lesions studies in subjects with apraxia, following left brain damage corroborate these findings. However, little is known about the structural connectivity underlying gesture production. We aimed to provide novel insights into the structural connectivity of the praxis network and how it is related to gesture production. Methods: Our sample consisted of 41 healthy subjects and of 40 patients with schizophrenia, demonstrating gesture impairments and structural network abnormalities. All participants performed a gesture production test, the test of upper limb apraxia and underwent diffusion weighted magnetic resonance imaging. Finsler geometry was used to investigate structural connectivity and graph theory to estimate global and local efficiency of the praxis network, which consists of 13 bilateral regions of interest. Results: Our findings showed an association of gesture production with network attributes and specific connections within the praxis network. Thus, global and local efficiency and most of the intra- and interhemispheric connections within the gesture network predicted gesture production across groups. Global efficiency of the praxis network further predicted gesture production only in the patient group. Local efficiency of many ROIs and connections of interest predicted production in patients at trend-level. In contrast, there were no significant or trend-level associations of gesture production with network attributes in controls. Discussion The results revealed an association of impaired gesture performance with structural alterations of the praxis network, including global and local efficiency and many connections of interest. Our findings are of great importance in the understanding of the structural correlates of gesture production and shed further light on the neural underpinnings of gesture deficits in a patient group with severe social deficits

Improving the predictive potential of diffusion MRI in schizophrenia using normative models-Towards subject-level classification.

Diffusion MRI studies consistently report group differences in white matter between individuals diagnosed with schizophrenia and healthy controls. Nevertheless, the abnormalities found at the group-level are often not observed at the individual level. Among the different approaches aiming to study white matter abnormalities at the subject level, normative modeling analysis takes a step towards subject-level predictions by identifying affected brain locations in individual subjects based on extreme deviations from a normative range. Here, we leveraged a large harmonized diffusion MRI dataset from 512 healthy controls and 601 individuals diagnosed with schizophrenia, to study whether normative modeling can improve subject-level predictions from a binary classifier. To this aim, individual deviations from a normative model of standard (fractional anisotropy) and advanced (free-water) dMRI measures, were calculated by means of age and sex-adjusted z-scores relative to control data, in 18 white matter regions. Even though larger effect sizes are found when testing for group differences in z-scores than are found with raw values (p < .001), predictions based on summary z-score measures achieved low predictive power (AUC < 0.63). Instead, we find that combining information from the different white matter tracts, while using multiple imaging measures simultaneously, improves prediction performance (the best predictor achieved AUC = 0.726). Our findings suggest that extreme deviations from a normative model are not optimal features for prediction. However, including the complete distribution of deviations across multiple imaging measures improves prediction, and could aid in subject-level classification

Sex differences in white matter alterations following repetitive subconcussive head impacts in collegiate ice hockey players☆

Objective: Repetitive subconcussive head impacts (RSHI) may lead to structural, functional, and metabolic alterations of the brain. While differences between males and females have already been suggested following a concussion, whether there are sex differences following exposure to RSHI remains unknown. The aim of this study was to identify and to characterize sex differences following exposure to RSHI. Methods: Twenty-five collegiate ice hockey players (14 males and 11 females, 20.6 ± 2.0 years), all part of the Hockey Concussion Education Project (HCEP), underwent diffusion-weighted magnetic resonance imaging (dMRI) before and after the Canadian Interuniversity Sports (CIS) ice hockey season 2011–2012 and did not experience a concussion during the season. Whole-brain tract-based spatial statistics (TBSS) were used to compare pre- and postseason imaging in both sexes for fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD). Pre- and postseason neurocognitive performance were assessed by the Immediate Post-Concussion Assessment and Cognitive Test (ImPACT). Results: Significant differences between the sexes were primarily located within the superior longitudinal fasciculus (SLF), the internal capsule (IC), and the corona radiata (CR) of the right hemisphere (RH). In significant voxel clusters (p < 0.05), decreases in FA (absolute difference pre- vs. postseason: 0.0268) and increases in MD (0.0002), AD (0.00008), and RD (0.00005) were observed in females whereas males showed no significant changes. There was no significant correlation between the change in diffusion scalar measures over the course of the season and neurocognitive performance as evidenced from postseason ImPACT scores. Conclusions: The results of this study suggest sex differences in structural alterations following exposure to RSHI. Future studies need to investigate further the underlying mechanisms and association with exposure and clinical outcomes

Where language meets action: The neural underpinnings of gesture performance in schizophrenia

Gestures are an integral part of social interactions, since they are crucially involved in nonverbal and verbal communication. They convey language that is expressed as motor action. Thus, successful gesturing depends on intact language and motor functions. Patients with schizophrenia show abnormalities in motor behavior, language, and consequently also in gesturing. Since gesture impairments predict poor course and outcome in schizophrenia, they may operate as an important treatment target. However, only little is known about the neural underpinnings of gesture performance in schizophrenia. This constitutes a highly promising approach, as schizophrenia is characterized by structural and functional brain abnormalities thought to contribute to its symptoms and aberrant behavior. A more profound understanding of disturbed gesture performance in schizophrenia can hence be gained by studying the neural underpinnings of motor behavior, language, and their interface gestures. Therefore, we aimed to investigate the structural correlates of impaired gesture performance in schizophrenia. Five studies were conducted to reach this aim. In a first step, we examined the neural underpinnings of both, the motor and the language dimension, which build the basis for successful gesturing. As brain dysconnectivity is a hallmark of schizophrenia, white matter (WM) correlates of the symptom dimensions might be particularly promising in explaining brain-behavior associations. Thus, in our first study, we explored the relationship between WM microstructure and the symptom dimensions of the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), with a special focus on the motor and language dimension. Our second study was conducted to gain more insights into the WM correlates of the disorganized speech dimension, since we assumed that a distinction of formal thought disorder (FTD) into a positive and negative pole might be crucial to identify biological correlates. Thus, we used a different rating scale compared to the DSM-5, namely the Bern Psychopathology Scale, which takes into account this differentiation of positive and negative FTD. In our third study, we shifted from WM to another marker of dysconnectivity and elaborated resting state functional connectivity within the motor system in patients with schizophrenia and its associations with disturbed motor behavior. In a second step, we examined the structural correlates of impaired gesture performance in schizophrenia. In our fourth study, we were interested whether possible cortical thickness alterations of regions within the praxis network are related to gesture production and recognition in schizophrenia. Finally, the aim of the fifth study was to explore the WM organization of the praxis network and how it might predict gesture production in a sample including both, patients with schizophrenia and healthy subjects. Thus, this study aimed to provide novel insights into the structural connectivity of the praxis network in general, whereby schizophrenia served as an ideal model displaying gesture deficits and WM abnormalities. Our findings revealed several associations of brain alterations with symptoms and aberrant behavior in patients with schizophrenia. The first three studies indicated that aberrant motor behavior and disorganized speech were related to specific brain alteration patterns. While disorganized speech was related to WM abnormalities in a predominantly fronto-temporal language network, aberrant motor behavior was linked to WM alterations of the motor tract and functional hyperconnectivity within the motor system. Moreover, the last two studies revealed a link between disturbed gesture performance with cortical thinning and reduced connectivity of the praxis network. More precisely, the fourth study detected cortical thinning in various areas of the praxis network in patients with gesture deficits, and an association of gesture recognition and cortical thinning in all patients. The fifth study revealed that gesture production in healthy subjects and patients with schizophrenia is predicted by global and local efficiency and by specific connections of the praxis network. Therefore, the findings of our last study contribute to a more comprehensive understanding about the neural correlates of gesture production in general. The focus of our studies was on gestures forming the interface of the motor and language dimension. Our results revealed several brain-behavior associations and support the view that schizophrenia symptoms derive from aberrant brain structure and function. Most importantly, we observed an association of impaired gesturing with structural alterations of the praxis network. This enhanced understanding of the neural basis of gesture deficits is of great importance for the comprehension of social dysfunction in schizophrenia and might further encourage researchers to develop novel interventions to improve the quality of life and functional outcome in patients with schizophrenia. In addition to pharmacological treatment, which affects social functioning rather via an indirect route, future studies could develop and apply social-cognitive trainings or non-invasive brain stimulation techniques that might directly target gesture performance in schizophrenia

Altered diffusion in motor white matter tracts in psychosis patients with catatonia.

Catatonia is a complex psychomotor symptom frequently observed in schizophrenia. Neural activity within the motor system is altered in catatonia. Likewise, white matter (WM) is also expected to be abnormal. The aim of this study was to test, if schizophrenia patients with catatonia show specific WM alterations. Forty-eight patients with schizophrenia and 43 healthy controls were included. Catatonia was currently present in 13 patients with schizophrenia. Tract-Based Spatial Statistics was used to test for differences in fractional anisotropy (FA) in the whole brain between the three groups. We detected a group effect (F-test) of WM within the corpus callosum (CC). In the t-test, patients with catatonia showed higher FA in many left lateralized WM clusters involved in motor behaviour compared to patients without catatonia, including the CC, internal and external capsule, superior longitudinal fascicle (SLF) and corticospinal tract (CST). Similarly, patients with catatonia showed also higher FA in the left internal capsule and left CST compared to healthy controls. In contrast, the group comparison between patients without catatonia and healthy controls revealed lower FA in many right lateralized clusters, comprising the CC, internal capsule, SLF, and inferior longitudinal fascicle in patients without catatonia. Our results are in line with the notion of an altered motor system in catatonia. Thus, our study provides evidence for increased WM connectivity, especially in motor tracts in schizophrenia patients with catatonia

Distinct Associations of Motor Domains in Relatives of Schizophrenia Patients—Different Pathways to Motor Abnormalities in Schizophrenia?

IntroductionAberrant motor function is an integral part of schizophrenia. In fact, abnormalities are frequently found in patients, in populations at risk, and in unaffected relatives. Motor abnormalities are suspected to be relevant for the clinical outcome and could probably predict the conversion from at-risk individuals to schizophrenia. Furthermore, motor function has been argued as endophenotype of the disorder. Yet, which particular motor domain may classify as a potential endophenotype is unknown. We aimed to compare schizophrenia patients, unaffected first-degree relatives and healthy controls for different motor domains. We expected impairments in all domains in patients and in some domains in relatives.MethodWe included 43 schizophrenia patients, 34 unaffected first-degree relatives of schizophrenia patients, and 29 healthy control subjects, matched for age, gender, and education level. We compared motor function of four motor domains between the groups. The domains comprise neurological soft signs (NSS), abnormal involuntary movements (dyskinesia), Parkinsonism, and fine motor function including simple [finger tapping (FT)] and complex fine motor function, (i.e., dexterity as measured with the coin rotation test). Furthermore, we tested the association of motor function of the four domains with working memory, frontal lobe function, and nonverbal intelligence for each group separately using within-group bivariate correlations.ResultsSchizophrenia patients showed poorer motor function in all tested domains compared to healthy controls. First-degree relatives had intermediate ratings with aberrant function in two motor domains. In detail, relatives had significantly more NSS and performed poorer in the FT task than controls. In contrast, complex fine motor function was intact in relatives. Relatives did not differ from controls in dyskinesia or Parkinsonism severity.DiscussionTaken together, schizophrenia patients have motor abnormalities in all tested domains. Thus, motor abnormalities are a key element of the disorder. Likewise, first-degree relatives presented motor deficits in two domains. A clear difference between relatives and healthy controls was found for NSS and FT. Thus, NSS and FT may be potential markers of vulnerability for schizophrenia. The lack of association between genetic risk and dyskinesia or Parkinsonism suggests distinct pathobiological mechanisms in the various motor abnormalities in schizophrenia