Cortico-cerebellar functional connectivity and sequencing of movements in schizophrenia

<p>Abstract</p> <p>Background</p> <p>Abnormal execution of several movements in a sequence is a frequent finding in schizophrenia. Successful performance of such motor acts requires correct integration of cortico-subcortical processes, particularly those related to cerebellar functions. Abnormal connectivity between cortical and cerebellar regions with resulting cognitive dysmetria has been proposed as the core dysfunction behind many signs and symptoms of schizophrenia. The aim of the present study was to assess if these proposed abnormalities in connectivity are a unifying feature of schizophrenia, or, rather, reflect a specific symptom domain of a heterogeneous disease. We predicted that abnormal functional connectivity between the motor cortex and cerebellum would be linked with abnormal performance of movement sequencing.</p> <p>Methods</p> <p>We examined 24 schizophrenia patients (SCH) and 24 age-, sex-, and handedness-matched healthy controls (HC) using fMRI during a modified finger-tapping task. The ability to perform movement sequencing was tested using the Neurological Evaluation Scale (NES). The subjects were categorized into two groups, with (SQ+) and without (SQ-) movement sequencing abnormalities, according to the NES-SQ score. The effects of diagnosis and movement sequencing abnormalities on the functional connectivity parameters between the motor cortex and cerebellum (MC-CRBL) and the supplementary motor cortex and cerebellum (SMA-CRBL) activated during the motor task were analyzed.</p> <p>Results</p> <p>We found no effect of diagnosis on the functional connectivity measures. There was, however, a significant effect on the SQ group: SQ + patients showed a lower level of MC-CRBL connectivity than SQ- patients and healthy controls. Moreover, the level of MC-CRBL and SMA-CRBL negatively correlated with the magnitude of NES-SQ abnormalities, but with no other NES domain.</p> <p>Conclusions</p> <p>Abnormal cortico-cerebellar functional connectivity during the execution of a motor task is linked with movement sequencing abnormalities in schizophrenia, but not with the diagnosis of schizophrenia per se. It seems that specific patterns of inter-regional connectivity are linked with corresponding signs and symptoms of clinically heterogeneous conditions such as schizophrenia.</p

Sparse regression for large data sets with outliers

The linear regression model remains an important workhorse for data scientists. However, many data sets contain many more predictors than observations. Besides, outliers, or anomalies, frequently occur. This paper proposes an algorithm for regression analysis that addresses these features typical for big data sets, which we call “sparse shooting S”. The resulting regression coefficients are sparse, meaning that many of them are set to zero, hereby selecting the most relevant predictors. A distinct feature of the method is its robustness with respect to outliers in the cells of the data matrix. The excellent performance of this robust variable selection and prediction method is shown in a simulation study. A real data application on car fuel consumption demonstrates its usefulness

Elevated levels of human endogenous retrovirus-W transcripts in blood cells from patients with first episode schizophrenia.

We previously reported on the differential presence of transcripts related to the human endogenous retrovirus (HERV)-W family in cerebrospinal fluid and plasma from patients with first-episode schizophrenia compared with control individuals. Whether this is a consequence of qualitative or quantitative differences in transcription of genomic regions harboring HERV-W elements is not known. The purpose of the present study was therefore to characterize the transcribed HERV-W elements in mononuclear cells obtained from 30 patients first hospitalized for schizophrenia-related psychosis and from 26 healthy control individuals. We observed elevated total levels of HERV-W gag (2.1-fold, P &lt; 0.01) but not env transcripts in the cells of patients compared with controls. By using the melting temperatures of the amplicons as a proxy marker for sequence identity, no absolute qualitative differences was detected between the two groups. Mapping of the detected transcripts identified several intronic and intergenic HERV-W elements transcribed in the cells, including elements previously considered transcriptionally silent. Element-specific assays revealed elevated levels of intronic transcripts containing HERV-W gag sequence from the putative gene PTD015 on chromosome 11q13.5 (1.6-fold, P &lt; 0.05) in the patients compared with the controls. Thus, studies aiming to further understanding of complex human disease such as schizophrenia may need to be extended beyond the strictly protein-coding fraction of the transcriptome

Elevated levels of human endogenous retrovirus-W transcripts in blood cells from patients with first episode schizophrenia.

We previously reported on the differential presence of transcripts related to the human endogenous retrovirus (HERV)-W family in cerebrospinal fluid and plasma from patients with first-episode schizophrenia compared with control individuals. Whether this is a consequence of qualitative or quantitative differences in transcription of genomic regions harboring HERV-W elements is not known. The purpose of the present study was therefore to characterize the transcribed HERV-W elements in mononuclear cells obtained from 30 patients first hospitalized for schizophrenia-related psychosis and from 26 healthy control individuals. We observed elevated total levels of HERV-W gag (2.1-fold, P < 0.01) but not env transcripts in the cells of patients compared with controls. By using the melting temperatures of the amplicons as a proxy marker for sequence identity, no absolute qualitative differences was detected between the two groups. Mapping of the detected transcripts identified several intronic and intergenic HERV-W elements transcribed in the cells, including elements previously considered transcriptionally silent. Element-specific assays revealed elevated levels of intronic transcripts containing HERV-W gag sequence from the putative gene PTD015 on chromosome 11q13.5 (1.6-fold, P < 0.05) in the patients compared with the controls. Thus, studies aiming to further understanding of complex human disease such as schizophrenia may need to be extended beyond the strictly protein-coding fraction of the transcriptome