scholarly journals Linking language features to clinical symptoms and multimodal imaging in individuals at clinical high risk for psychosis

2020 ◽  
Vol 63 (1) ◽  
Author(s):  
S. S. Haas ◽  
G. E. Doucet ◽  
S. Garg ◽  
S. N. Herrera ◽  
C. Sarac ◽  
...  
Keyword(s):  
High Risk ◽  
Functional Connectivity ◽  
Language Processing ◽  
Resting State ◽  
Clinical Symptoms ◽  
Syntactic Complexity ◽  
Clinical High Risk ◽  
Linguistic Features ◽  
Brain Morphometry ◽  
Language Network

Abstract Background. Abnormalities in the semantic and syntactic organization of speech have been reported in individuals at clinical high-risk (CHR) for psychosis. The current study seeks to examine whether such abnormalities are associated with changes in brain structure and functional connectivity in CHR individuals. Methods. Automated natural language processing analysis was applied to speech samples obtained from 46 CHR and 22 healthy individuals. Brain structural and resting-state functional imaging data were also acquired from all participants. Sparse canonical correlation analysis (sCCA) was used to ascertain patterns of covariation between linguistic features, clinical symptoms, and measures of brain morphometry and functional connectivity related to the language network. Results. In CHR individuals, we found a significant mode of covariation between linguistic and clinical features (r = 0.73; p = 0.003), with negative symptoms and bizarre thinking covarying mostly with measures of syntactic complexity. In the entire sample, separate sCCAs identified a single mode of covariation linking linguistic features with brain morphometry (r = 0.65; p = 0.05) and resting-state network connectivity (r = 0.63; p = 0.01). In both models, semantic and syntactic features covaried with brain structural and functional connectivity measures of the language network. However, the contribution of diagnosis to both models was negligible. Conclusions. Syntactic complexity appeared sensitive to prodromal symptoms in CHR individuals while the patterns of brain-language covariation seemed preserved. Further studies in larger samples are required to establish the reproducibility of these findings.

scholarly journals Dysregulation of complement and coagulation pathways: emerging mechanisms in the development of psychosis

2021 ◽  
Author(s):  
Meike Heurich ◽  
Melanie Föcking ◽  
David Mongan ◽  
Gerard Cagney ◽  
David R. Cotter
Keyword(s):  
High Risk ◽  
Psychotic Disorder ◽  
Psychotic Disorders ◽  
Clinical Symptoms ◽  
First Episode Psychosis ◽  
Specific Protein ◽  
First Episode ◽  
Clinical High Risk ◽  
Blood Proteins ◽  
Episode Psychosis

AbstractEarly identification and treatment significantly improve clinical outcomes of psychotic disorders. Recent studies identified protein components of the complement and coagulation systems as key pathways implicated in psychosis. These specific protein alterations are integral to the inflammatory response and can begin years before the onset of clinical symptoms of psychotic disorder. Critically, they have recently been shown to predict the transition from clinical high risk to first-episode psychosis, enabling stratification of individuals who are most likely to transition to psychotic disorder from those who are not. This reinforces the concept that the psychosis spectrum is likely a central nervous system manifestation of systemic changes and highlights the need to investigate plasma proteins as diagnostic or prognostic biomarkers and pathophysiological mediators. In this review, we integrate evidence of alterations in proteins belonging to the complement and coagulation protein systems, including the coagulation, anticoagulation, and fibrinolytic pathways and their dysregulation in psychosis, into a consolidated mechanism that could be integral to the progression and manifestation of psychosis. We consolidate the findings of altered blood proteins relevant for progression to psychotic disorders, using data from longitudinal studies of the general population in addition to clinical high-risk (CHR) individuals transitioning to psychotic disorder. These are compared to markers identified from first-episode psychosis and schizophrenia as well as other psychosis spectrum disorders. We propose the novel hypothesis that altered complement and coagulation plasma levels enhance their pathways’ activating capacities, while low levels observed in key regulatory components contribute to excessive activation observed in patients. This hypothesis will require future testing through a range of experimental paradigms, and if upheld, complement and coagulation pathways or specific proteins could be useful diagnostic or prognostic tools and targets for early intervention and preventive strategies.

scholarly journals The effect of amyloid deposition on longitudinal resting-state functional connectivity in cognitively normal older adults

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Chemin Lin ◽  
Maria Ly ◽  
Helmet T. Karim ◽  
Wenjing Wei ◽  
Beth E. Snitz ◽  
...  
Keyword(s):  
Neural Networks ◽  
Older Adults ◽  
Cognitive Function ◽  
Functional Connectivity ◽  
Resting State ◽  
Clinical Symptoms ◽  
Rate Of Change ◽  
Resting State Functional Connectivity ◽  
Cognitive Changes ◽  
Cognitively Normal

Abstract Background Pathological processes contributing to Alzheimer’s disease begin decades prior to the onset of clinical symptoms. There is significant variation in cognitive changes in the presence of pathology, functional connectivity may be a marker of compensation to amyloid; however, this is not well understood. Methods We recruited 64 cognitively normal older adults who underwent neuropsychological testing and biannual magnetic resonance imaging (MRI), amyloid imaging with Pittsburgh compound B (PiB)-PET, and glucose metabolism (FDG)-PET imaging for up to 6 years. Resting-state MRI was used to estimate connectivity of seven canonical neural networks using template-based rotation. Using voxel-wise paired t-tests, we identified neural networks that displayed significant changes in connectivity across time. We investigated associations among amyloid and longitudinal changes in connectivity and cognitive function by domains. Results Left middle frontal gyrus connectivity within the memory encoding network increased over time, but the rate of change was lower with greater amyloid. This was no longer significant in an analysis where we limited the sample to only those with two time points. We found limited decline in cognitive domains overall. Greater functional connectivity was associated with better attention/processing speed and executive function (independent of time) in those with lower amyloid but was associated with worse function with greater amyloid. Conclusions Increased functional connectivity serves to preserve cognitive function in normal aging and may fail in the presence of pathology consistent with compensatory models.

scholarly journals Clinical subtypes that predict conversion to psychosis: A canonical correlation analysis study from the ShangHai At Risk for Psychosis program

2019 ◽  
Vol 54 (5) ◽  
pp. 482-495 ◽  
Author(s):  
TianHong Zhang ◽  
XiaoChen Tang ◽  
HuiJun Li ◽  
Kristen A Woodberry ◽  
Emily R Kline ◽  
...  
Keyword(s):  
At Risk ◽  
Cluster Analysis ◽  
High Risk ◽  
Correlation Analysis ◽  
Canonical Correlation Analysis ◽  
Canonical Correlation ◽  
Clinical Symptoms ◽  
Structured Interview ◽  
Two Dimensions ◽  
Clinical High Risk

Objective: Since only 30% or fewer of individuals at clinical high risk convert to psychosis within 2 years, efforts are underway to refine risk identification strategies to increase their predictive power. The clinical high risk is a heterogeneous syndrome presenting with highly variable clinical symptoms and cognitive dysfunctions. This study investigated whether subtypes defined by baseline clinical and cognitive features improve the prediction of psychosis. Method: Four hundred clinical high-risk subjects from the ongoing ShangHai At Risk for Psychosis program were enrolled in a prospective cohort study. Canonical correlation analysis was applied to 289 clinical high-risk subjects with completed Structured Interview for Prodromal Syndromes and cognitive battery tests at baseline, and at least 1-year follow-up. Canonical variates were generated by canonical correlation analysis and then used for hierarchical cluster analysis to produce subtypes. Kaplan–Meier survival curves were constructed from the three subtypes to test their utility further in predicting psychosis. Results: Canonical correlation analysis determined two linear combinations: (1) negative symptom and functional deterioration-related cognitive features, and (2) Positive symptoms and emotional disorganization-related cognitive features. Cluster analysis revealed three subtypes defined by distinct and relatively homogeneous patterns along two dimensions, comprising 14.2% (subtype 1, n = 41), 37.4% (subtype 2, n = 108) and 48.4% (subtype 3, n = 140) of the sample, and each with distinctive features of clinical and cognitive performance. Those with subtype 1, which is characterized by extensive negative symptoms and cognitive deficits, appear to have the highest risk for psychosis. The conversion risk for subtypes 1–3 are 39.0%, 11.1% and 18.6%, respectively. Conclusion: Our results define important subtypes within clinical high-risk syndromes that highlight clinical symptoms and cognitive features that transcend current diagnostic boundaries. The three different subtypes reflect significant differences in clinical and cognitive characteristics as well as in the risk of conversion to psychosis.

scholarly journals Sex Difference in Language Processing in Patients With Malignant Brain Tumors

Neurosurgery ◽  
2019 ◽  
Vol 66 (Supplement_1) ◽  
Author(s):  
Shun Yao ◽  
Einat Liebenthal ◽  
Parikshit Juvekar ◽  
Adomas Bunevicius ◽  
Matthew Vera ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Brain Tumors ◽  
Language Processing ◽  
Resting State ◽  
Precentral Gyrus ◽  
Language Function ◽  
Brain Areas ◽  
Brain Organization ◽  
Malignant Brain Tumors ◽  
Parietal Lobule

Abstract INTRODUCTION Numerous differences between males and females in brain organization have been described including in the development, performance, and lateralization of language function. However, there is very limited knowledge of whether language processing differs across sex in patients with brain lesions. In particular, malignant brain tumors (MBT) demonstrate significant sex differences in incidence and long-term survival. Given the importance of brain organization and planning surgical treatment for patients with brain tumors, we investigated the effect of sex on the organization of language in a cohort of patients with MBT. METHODS In the current study, we carried out a retrospective analysis in 47 patients with MBT (22 females, 25 males), retrieving their clinical characteristics and task-based and resting-state functional magnetic resonance image (fMRI) data from our clinical database. General Linear Model (GLM) and region-of-interest (ROI) based resting-state functional connectivity (RSFC) analyses were applied to explore the effect of sex on language tasks associated activations and functional connectivity. RESULTS Across the Sentence Completion task and Antonym Generation task, female patients showed greater activation volumes in the left inferior frontal gyrus, right precuneus, and left superior parietal lobule, while male patients showed larger clusters of activation of the left supplemental motor area (SMA), left inferior parietal lobule (IPL), left precuneus, bilateral precentral gyrus, and right supramarginal gyrus (SMG). Furthermore, the left SMA was a highly sex-specific brain area during the language performance, and it showed stronger resting-state correlations with brain areas within the intrinsic language network in females, while it showed stronger resting-state connections with brain areas involving the visuomotor/higher level cognitive functions in males. CONCLUSION These findings enhance our understanding of the role of sex in language organization in patients with MBT, helping neurosurgeons assess surgical risk and plan surgery in patients with MBT to best preserve language function.

scholarly journals Resting-state functional connectivity of emotion regulation networks in euthymic and non-euthymic bipolar disorder patients

2016 ◽  
Vol 34 ◽  
pp. 56-63 ◽  
Author(s):  
G. Rey ◽  
C Piguet ◽  
A Benders ◽  
S Favre ◽  
SB Eickhoff ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Functional Connectivity ◽  
Resting State ◽  
Clinical Symptoms ◽  
Mood State ◽  
A Priori ◽  
Emotion Processing ◽  
Population Sample ◽  
Small Population ◽  
Resting State Functional Connectivity

AbstractBackgroundPrevious functional magnetic resonance imaging studies in bipolar disorder (BD) have evidenced changes in functional connectivity (FC) in brain areas associated with emotion processing, but how these changes vary with mood state and specific clinical symptoms is not fully understood.MethodsWe investigated resting-state FC between a priori regions of interest (ROIs) from the default-mode network and key structures for emotion processing and regulation in 27 BD patients and 27 matched healthy controls. We further compared connectivity patterns in subgroups of 15 euthymic and 12 non-euthymic patients and tested for correlations of the connectivity strength with measures of mood, anxiety, and rumination tendency. No correction for multiple comparisons was applied given the small population sample and pre-defined target ROIs.ResultsOverall, regardless of mood state, BD patients exhibited increased FC of the left amygdala with left sgACC and PCC, relative to controls. In addition, non-euthymic BD patients showed distinctive decrease in FC between right amygdala and sgACC, whereas euthymic patients showed lower FC between PCC and sgACC. Euthymic patients also displayed increased FC between sgACC and right VLPFC. The sgACC–PCC and sgACC–left amygdala connections were modulated by rumination tendency in non-euthymic patients, whereas the sgACC-VLPFC connection was modulated by both the current mood and tendency to ruminate.ConclusionsOur results suggest that sgACC-amygdala coupling is critically affected during mood episodes, and that FC of sgACC play a pivotal role in mood normalization through its interactions with the VLPFC and PCC. However, these preliminary findings require replication with larger samples of patients.

Timing dysfunction and cerebellar resting state functional connectivity abnormalities in youth at clinical high-risk for psychosis

2020 ◽  
pp. 1-10 ◽  
Author(s):  
K. Juston Osborne ◽  
Katherine S. F. Damme ◽  
Tina Gupta ◽  
Derek J. Dean ◽  
Jessica A. Bernard ◽  
...  
Keyword(s):  
High Risk ◽  
Resting State ◽  
Negative Symptoms ◽  
Brain Regions ◽  
Internal Clock ◽  
Clinical High Risk ◽  
Resting State Functional Connectivity ◽  
Schizophrenia Spectrum ◽  
Temporal Bisection Task ◽  
Resting State Connectivity

Abstract Background Consistent with pathophysiological models of psychosis, temporal disturbances in schizophrenia spectrum populations may reflect abnormal cortical (e.g. prefrontal cortex) and subcortical (e.g. striatum) cerebellar connectivity. However, few studies have examined associations between cerebellar connectivity and timing dysfunction in psychosis populations, and none have been conducted in youth at clinical high-risk (CHR) for psychosis. Thus, it is currently unknown if impairments in temporal processes are present in CHR youth or how they may be associated with cerebellar connectivity and worsening of symptoms. Methods A total of 108 (56 CHR/52 controls) youth were administered an auditory temporal bisection task along with a resting state imaging scan to examine cerebellar resting state connectivity. Positive and negative symptoms at baseline and 12 months later were also quantified. Results Controlling for alcohol and cannabis use, CHR youth exhibited poorer temporal accuracy compared to controls, and temporal accuracy deficits were associated with abnormal connectivity between the bilateral anterior cerebellum and a right caudate/nucleus accumbens striatal cluster. Poor temporal accuracy accounted for 11% of the variance in worsening of negative symptoms over 12 months. Conclusions Behavioral findings suggest CHR youth perceive durations of auditory tones as shortened compared to objective time, which may indicate a slower internal clock. Poorer temporal accuracy in CHR youth was associated with abnormalities in brain regions involved in an important cerebellar network implicated in prominent pathophysiological models of psychosis. Lastly, temporal accuracy was associated with worsening of negative symptoms across 12 months, suggesting temporal dysfunction may be sensitive to illness progression.

scholarly journals Reduced higher-dimensional resting state fMRI dynamism in clinical high-risk individuals for schizophrenia identified by meta-state analysis

2018 ◽  
Vol 201 ◽  
pp. 217-223 ◽  
Author(s):  
Eva Mennigen ◽  
Robyn L. Miller ◽  
Barnaly Rashid ◽  
Susanna L. Fryer ◽  
Rachel L. Loewy ◽  
...  
Keyword(s):  
High Risk ◽  
Resting State ◽  
Resting State Fmri ◽  
Clinical High Risk ◽  
Higher Dimensional ◽  
State Analysis

scholarly journals Baseline Cortical Thickness Reductions in Clinical High Risk for Psychosis: Brain Regions Associated with Conversion to Psychosis Versus Non-Conversion as Assessed at One-Year Follow-Up in the Shanghai-At-Risk-for-Psychosis (SHARP) Study

2020 ◽  
Author(s):  
Elisabetta C Del Re ◽  
William S Stone ◽  
Sylvain Bouix ◽  
Johanna Seitz ◽  
Victor Zeng ◽  
...  
Keyword(s):  
High Risk ◽  
Language Processing ◽  
Cortical Thickness ◽  
Brain Regions ◽  
Group Differences ◽  
Clinical High Risk ◽  
Pars Opercularis ◽  
One Year ◽  
First Time

Abstract Objective To assess cortical thickness (CT) and surface area (SA) of frontal, temporal, and parietal brain regions in a large clinical high risk for psychosis (CHR) sample, and to identify cortical brain abnormalities in CHR who convert to psychosis and in the whole CHR sample, compared with the healthy controls (HC). Methods Magnetic resonance imaging, clinical, and cognitive data were acquired at baseline in 92 HC, 130 non-converters, and 22 converters (conversion assessed at 1-year follow-up). CT and SA at baseline were calculated for frontal, temporal, and parietal subregions. Correlations between regions showing group differences and clinical scores and age were also obtained. Results CT but not SA was significantly reduced in CHR compared with HC. Two patterns of findings emerged: (1) In converters, CT was significantly reduced relative to non-converters and controls in the banks of superior temporal sulcus, Heschl’s gyrus, and pars triangularis and (2) CT in the inferior parietal and supramarginal gyrus, and at trend level in the pars opercularis, fusiform, and middle temporal gyri was significantly reduced in all high-risk individuals compared with HC. Additionally, reduced CT correlated significantly with older age in HC and in non-converters but not in converters. Conclusions These results show for the first time that fronto-temporo-parietal abnormalities characterized all CHR, that is, both converters and non-converters, relative to HC, while CT abnormalities in converters relative to CHR-NC and HC were found in core auditory and language processing regions.

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