Developing antisense oligonucleotides for a mutation-induced, ultra-rare neurological disorder using patient-derived cellular models.

Mutations in the gene are the cause of an ultra-rare neurological disorder characterized by intellectual disability, impaired speech, motor delay, and hypotonia evolving to spasticity, central sleep apnea, and premature death (SPG49 or HSAN9; OMIM: 615031). Little is known about the biological function of TECPR2, and there are currently no available disease-modifying therapies for this disease. Here we describe implementation of an antisense oligonucleotide (ASO) exon-skipping strategy targeting c.

Functional MRI reveals evidence of a self-positivity bias in the medial prefrontal cortex during the comprehension of social vignettes.

A large literature in social neuroscience has associated the medial prefrontal cortex (mPFC) with the processing of self-related information. However, only recently have social neuroscience studies begun to consider the large behavioral literature showing a strong self-positivity bias, and these studies have mostly focused on its correlates during self-related judgments and decision-making. We carried out a functional MRI (fMRI) study to ask whether the mPFC would show effects of the self-positivity bias in a paradigm that probed participants' self-concept without any requirement of explicit self-judgment.

Neural evidence for Bayesian trial-by-trial adaptation on the N400 during semantic priming.

When semantic information is activated by a context prior to new bottom-up input (i.e. when a word is predicted), semantic processing of that incoming word is typically facilitated, attenuating the amplitude of the N400 event related potential (ERP) - a direct neural measure of semantic processing.

Multimodal neuroimaging evidence for looser lexico-semantic networks in schizophrenia:Evidence from masked indirect semantic priming.

It has been hypothesized that schizophrenia is characterized by overly broad automatic activity within lexico-semantic networks. We used two complementary neuroimaging techniques, Magnetoencephalography (MEG) and functional Magnetic Resonance Imaging (fMRI), in combination with a highly automatic indirect semantic priming paradigm, to spatiotemporally localize this abnormality in the brain. Eighteen people with schizophrenia and 20 demographically-matched control participants viewed target words ("bell") preceded by directly related ("church"), indirectly related ("priest"), or unrelated ("hammer") prime words in MEG and fMRI sessions.

Integrated assessment of visual perception abnormalities in psychotic disorders and relationship with clinical characteristics.

Background: The visual system is recognized as an important site of pathology and dysfunction in schizophrenia. In this study, we evaluated different visual perceptual functions in patients with psychotic disorders using a potentially clinically applicable task battery and assessed their relationship with symptom severity in patients, and with schizotypal features in healthy participants.

Methods: Five different areas of visual functioning were evaluated in patients with schizophrenia and schizoaffective disorder (n = 28) and healthy control subjects (n = 31) using a battery that included visuospatial working memory (VSWM), velocity discrimination (VD), contour integration, visual context processing, and backward masking tasks.

Spared bottom-up but impaired top-down interactive effects during naturalistic language processing in schizophrenia: evidence from the visual-world paradigm.

Background: People with schizophrenia process language in unusual ways, but the causes of these abnormalities are unclear. In particular, it has proven difficult to empirically disentangle explanations based on impairments in the top-down processing of higher level information from those based on the bottom-up processing of lower level information.

Methods: To distinguish these accounts, we used visual-world eye tracking, a paradigm that measures spoken language processing during real-world interactions.

Priming production: Neural evidence for enhanced automatic semantic activity preceding language production in schizophrenia.

Introduction: Lexico-semantic disturbances are considered central to schizophrenia. Clinically, their clearest manifestation is in language production. However, most studies probing their underlying mechanisms have used comprehension or categorization tasks.

Vivid: How valence and arousal influence word processing under different task demands.

In this study, we used event-related potentials to examine how different dimensions of emotion-valence and arousal-influence different stages of word processing under different task demands. In two experiments, two groups of participants viewed the same single emotional and neutral words while carrying out different tasks. In both experiments, valence (pleasant, unpleasant, and neutral) was fully crossed with arousal (high and low).

Friendly drug-dealers and terrifying puppies: affective primacy can attenuate the N400 effect in emotional discourse contexts.

Words that are semantically congruous with their preceding discourse context are easier to process than words that are semantically incongruous with their context. This facilitation of semantic processing is reflected by an attenuation of the N400 event-related potential (ERP). We asked whether this was true of emotional words in emotional contexts where discourse congruity was conferred through emotional valence.