More organized white matter is associated with positivity bias in older adults.

On average, healthy older adults prefer positive over neutral or negative stimuli. This positivity bias is related to memory and attention processes and is linked to the function and structure of several interconnected brain areas. However, the relationship between the positivity bias and white matter integrity remains elusive. The present study examines how white matter organization relates to the degree of the positivity bias among older adults. We collected imaging and behavioral data from 25 individuals (12 females, 13 males, and a mean age of 77.32). Based on a functional memory task, we calculated a Pos-Neg score, reflecting the memory for positively valenced information over negative information, and a Pos-Neu score, reflecting the memory for positively valenced information over neutral information. Diffusion-weighted magnetic resonance imaging data were processed using Tract-Based Spatial Statistics. We performed two non-parametric permutation tests to correlate whole brain white matter integrity and the Pos-Neg and Pos-Neu scores while controlling for age, sex, and years of education. We observed a statistically significant positive association between the Pos-Neu score and white matter integrity in multiple brain connections, mostly frontal. The results did not remain significant when including verbal episodic memory as an additional covariate. Our study indicates that the positivity bias in memory in older adults is associated with more organized white matter in the connections of the frontal brain. While these frontal areas are critical for memory and executive processes and have been related to pathological aging, more extensive studies are needed to fully understand their role in the positivity bias and the potential for therapeutic interventions.

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.

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.

Structural organization of the praxis network predicts gesture production: Evidence from healthy subjects and patients with schizophrenia.

Hand gestures are an integral part of social interactions and communication. Several imaging studies in healthy subjects and lesion studies in patients with apraxia suggest the praxis network for gesture production, involving mainly left inferior frontal, posterior parietal and temporal regions. However, little is known about the structural connectivity underlying gesture production. We recruited 41 healthy participants and 39 patients with schizophrenia. All participants performed a gesture production test, the Test of Upper Limb Apraxia, and underwent diffusion tensor imaging. We hypothesized that gesture production is associated with structural network connectivity as well as with tract integrity. We defined the praxis network as an undirected graph comprised of 13 bilateral regions of interest and derived measures of local and global structural connectivity and tract integrity from Finsler geometry. We found an association of gesture deficit with reduced global and local efficiency of the praxis network. Furthermore, reduced tract integrity, for example in the superior longitudinal fascicle, arcuate fascicle or corpus callosum were related to gesture deficits. Our findings contribute to the understanding of structural correlates of gesture production as they first present diffusion tensor imaging data in a combined sample of healthy subjects and a patient cohort with gestural deficits.

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.

Dysbalanced Resting-State Functional Connectivity Within the Praxis Network Is Linked to Gesture Deficits in Schizophrenia.

Patients with schizophrenia frequently present deficits in gesture production and interpretation, greatly affecting their communication skills. As these gesture deficits can be found early in the course of illness and as they can predict later outcomes, exploring their neural basis may lead to a better understanding of schizophrenia. While gesturing has been reported to rely on a left lateralized network of brain regions, termed praxis network, in healthy subjects and lesioned patients, studies in patients with schizophrenia are sparse. It is currently unclear whether within-network connectivity at rest is linked to gesture deficit. Here, we compared the functional connectivity between regions of the praxis network at rest between 46 patients and 44 healthy controls. All participants completed a validated test of hand gesture performance before resting-state functional magnetic resonance imaging (fMRI) was acquired. Patients performed gestures poorer than controls in all categories and domains. In patients, we also found significantly higher resting-state functional connectivity between left precentral gyrus and bilateral superior and inferior parietal lobule. Likewise, patients had higher connectivity from right precentral gyrus to left inferior and bilateral superior parietal lobule (SPL). In contrast, they exhibited lower connectivity between bilateral superior temporal gyrus (STG). Connectivity between right precentral gyrus and left SPL, as well as connectivity between bilateral STG, correlated with gesture performance in healthy controls. We failed to detect similar correlations in patients. We suggest that altered resting-state functional connectivity within the praxis network perturbs correct gesture planning in patients, reflecting the gesture deficit often seen in schizophrenia.

Anatomical integrity within the inferior fronto-occipital fasciculus and semantic processing deficits in schizophrenia spectrum disorders.

The core symptoms of schizophrenia spectrum disorders (SSD) include abnormal semantic processing which may rely on the ventral language stream of the human brain. Thus, structural disruption of the ventral language stream may play an important role in semantic deficits observed in SSD patients. Therefore, we compared white matter tract integrity in SSD patients and healthy controls using diffusion tensor imaging combined with probabilistic fiber tractography. For the ventral language stream, we assessed the inferior fronto-occipital fasciculus [IFOF], inferior longitudinal fasciculus, and uncinate fasciculus. The arcuate fasciculus and corticospinal tract were used as control tracts. In SSD patients, the relationship between semantic processing impairments and tract integrity was analyzed separately. Three-dimensional tract reconstructions were performed in 45/44 SSD patients/controls ("Bern sample") and replicated in an independent sample of 24/24 SSD patients/controls ("Basel sample"). Multivariate analyses of fractional anisotropy, mean, axial, and radial diffusivity of the left IFOF showed significant differences between SSD patients and controls (p(FDR-corr) < 0.001, ηp2 = 0.23) in the Bern sample. Axial diffusivity (AD) of the left UF was inversely correlated with semantic impairments (r = -0.454, p(FDR-corr) = 0.035). In the Basel sample, significant group differences for the left IFOF were replicated (p < .01, ηp2 = 0.29), while the correlation between AD of the left IFOF and semantic processing decline (r = -0.376, p = .09) showed a statistical trend. No significant effects were found for the dorsal language stream. This is direct evidence for the importance of the integrity of the ventral language stream, in particular the left IFOF, in semantic processing deficits in SSD.

Single Session Transcranial Magnetic Stimulation Ameliorates Hand Gesture Deficits in Schizophrenia.

Social interaction is impaired in schizophrenia, including the use of hand gestures, which is linked to poor social perception and outcome. Brain imaging suggests reduced neural activity in a left-lateralized frontoparietal network during gesture preparation; therefore, gesturing might be improved through facilitation of left hemispheric brain areas or via disruption of interhemispheric inhibition from the right homolog. This study tested whether repetitive transcranial magnetic stimulation (rTMS) protocols would improve gesture performance in schizophrenia. This randomized, placebo-controlled, double-blind, crossover trial applied 3 different protocols of rTMS separated by 48 h. Twenty right-handed schizophrenia patients and 20 matched healthy controls received facilitatory intermittent theta burst stimulation (iTBS) over the left inferior frontal gyrus (IFG), inhibitory continuous theta burst stimulation (cTBS) over right inferior parietal lobe (IPL), and placebo over left IPL in randomized order. Primary outcome was change in the test of upper limb apraxia (TULIA), rated from video recordings of hand gesture performance. Secondary outcome was change in manual dexterity using the coin rotation task. Participants improved on both tasks following rTMS compared with baseline. Only patients improved gesture performance following right IPL cTBS compared with placebo (P = .013). The results of the coin rotation parallel those of the TULIA, with improvements following right IPL cTBS in patients (P = .001). Single sessions of cTBS on the right IPL substantially improved both gesture performance accuracy and manual dexterity. The findings point toward an inhibition of interhemispheric rivalry as a potential mechanism of action.

Increased structural connectivity of the medial forebrain bundle in schizophrenia spectrum disorders is associated with delusions of paranoid threat and grandiosity.

In many cases delusions in schizophrenia spectrum disorders (SSD) are driven by strong emotions such as feelings of paranoia or grandiosity. We refer to these extreme emotional experiences as psychotic affectivity. We hypothesized that increased structural connectivity of the supero-lateral medial forebrain bundle (slMFB), a major tract of the reward system, is associated with delusional psychotic affectivity. Forty-six patients with SSD and 44 healthy controls (HC) underwent diffusion weighted magnetic resonance imaging (DW-MRI)-scans. The slMFB and a comparison tract (corticospinal tract) were reconstructed using diffusion tensor imaging (DTI)-based tractography. Fractional anisotropy (FA) was sampled across the tracts. We used a mixed-model analyses of variance controlling for age and gender to compare FA of bilateral slMFB between SSD-patients and HC. Correlations of FA of bilateral slMFB and the PANSS-positive item delusions were calculated. In addition, FA was compared between three clinically homogeneous SSD-subgroups in terms of psychotic affectivity (severe, mild and no PA, sPA, mPA, nPA) and HC. FA of the slMFB did not differ between all SSD-patients and HC. In SSD-patients there was a positive correlation between delusions and FA in bilateral slMFB. Likewise, SSD-subgroups of psychotic affectivity and HC differed significantly in FA of the slMFB. Results were driven by higher FA in the right slMFB in sPA as compared to nPA and to HC. There was no significant effect for the comparison tract. In conclusion, increased structural connectivity of the slMFB may underlie delusional experiences of paranoia and grandiosity in SSD.

Aberrant fronto-striatal connectivity and fine motor function in schizophrenia.

Abnormal fine motor function is a frequent finding in schizophrenia and has been linked to structural and functional brain alterations. However, whether fine motor function is related to functional alterations within the motor system remains unclear. The aim of this study was to assess whether abnormalities in resting-state functional connectivity are present in schizophrenia patients and to investigate how these abnormalities may be related to fine motor function. We examined 19 schizophrenia patients and 16 healthy controls using resting-state functional connectivity for 11 bilateral regions of interest. Fine motor function was assessed on a set of copying tasks and the Symbol-Digit-Substitution Test. We found significantly reduced functional connectivity between the left caudate nucleus and bilateral dorsolateral prefrontal cortex (DLPFC) and between the left putamen and bilateral supplementary motor area (SMA) proper in patients compared to controls. Altered connectivity from DLPFC to caudate nucleus was related to fine motor tasks, which are sensitive to psychomotor speed, whereas aberrant connectivity between the SMA proper and putamen was associated to both, fine motor task, which are sensitive to psychomotor speed and to speed of information processing. Our findings emphasize the role of fronto-striatal connections in the pathogenesis of fine motor impairments in schizophrenia.

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

INTRODUCTION: Aberrant 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. METHOD: We 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. RESULTS: Schizophrenia 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. DISCUSSION: Taken 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.

White matter correlates of the disorganized speech dimension in schizophrenia.

Disorganized speech is related to functional abnormalities in schizophrenia. To test the association between formal thought disorders (FTDs) and white matter microstructure, we applied a behavioral rating and diffusion tensor imaging in 61 patients with schizophrenia spectrum disorders. The Bern Psychopathology Scale was used to rate the dimension of language abnormalities ranging from negative FTDs, basically unaltered speech, to positive FTDs. Tract-based spatial statistics indicated increased fractional anisotropy in left hemispheric pathways of the language system in patients with negative FTDs. Thus, altered white matter properties in relevant fiber tracts may represent vulnerability to specific formal thought disorders.

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.

Aberrant Hyperconnectivity in the Motor System at Rest Is Linked to Motor Abnormalities in Schizophrenia Spectrum Disorders.

Motor abnormalities are frequently observed in schizophrenia and structural alterations of the motor system have been reported. The association of aberrant motor network function, however, has not been tested. We hypothesized that abnormal functional connectivity would be related to the degree of motor abnormalities in schizophrenia. In 90 subjects (46 patients) we obtained resting stated functional magnetic resonance imaging (fMRI) for 8 minutes 40 seconds at 3T. Participants further completed a motor battery on the scanning day. Regions of interest (ROI) were cortical motor areas, basal ganglia, thalamus and motor cerebellum. We computed ROI-to-ROI functional connectivity. Principal component analyses of motor behavioral data produced 4 factors (primary motor, catatonia and dyskinesia, coordination, and spontaneous motor activity). Motor factors were correlated with connectivity values. Schizophrenia was characterized by hyperconnectivity in 3 main areas: motor cortices to thalamus, motor cortices to cerebellum, and prefrontal cortex to the subthalamic nucleus. In patients, thalamocortical hyperconnectivity was linked to catatonia and dyskinesia, whereas aberrant connectivity between rostral anterior cingulate and caudate was linked to the primary motor factor. Likewise, connectivity between motor cortex and cerebellum correlated with spontaneous motor activity. Therefore, altered functional connectivity suggests a specific intrinsic and tonic neural abnormality in the motor system in schizophrenia. Furthermore, altered neural activity at rest was linked to motor abnormalities on the behavioral level. Thus, aberrant resting state connectivity may indicate a system out of balance, which produces characteristic behavioral alterations.

Cerebral white matter structure is associated with DSM-5 schizophrenia symptom dimensions.

Diffusion tensor imaging (DTI) studies have provided evidence of widespread white matter (WM) abnormalities in schizophrenia. Although these abnormalities appear clinically significant, the relationship to specific clinical symptoms is limited and heterogeneous. This study examined the association between WM microstructure and the severity of the five main DSM-5 schizophrenia symptom dimensions. DTI was measured in forty patients with schizophrenia spectrum disorders. Using Tract-Based Spatial Statistics controlling for age, gender and antipsychotic dosage, our analyses revealed significant negative relationships between WM microstructure and two DSM-5 symptom dimensions: Whereas abnormal psychomotor behavior was particularly related to WM of motor tracts, negative symptoms were associated with WM microstructure of the prefrontal and right temporal lobes. However, we found no associations between WM microstructure and delusions, hallucinations or disorganized speech. These data highlight the relevance of characteristic WM disconnectivity patterns as markers for negative symptoms and abnormal psychomotor behavior in schizophrenia and provide evidence for relevant associations between brain structure and aberrant behavior.