Modulation of habenular and nucleus accumbens functional connectivity by ketamine in major depression.

Introduction: Major depressive disorder (MDD) is associated with dysfunctional reward processing, which involves functional circuitry of the habenula (Hb) and nucleus accumbens (NAc). Since ketamine elicits rapid antidepressant and antianhedonic effects in MDD, this study sought to investigate how serial ketamine infusion (SKI) treatment modulates static and dynamic functional connectivity (FC) in Hb and NAc functional networks.

Methods: MDD participants (n = 58, mean age = 40.

Ketamine treatment modulates habenular and nucleus accumbens static and dynamic functional connectivity in major depression.

Dysfunctional reward processing in major depressive disorder (MDD) involves functional circuitry of the habenula (Hb) and nucleus accumbens (NAc). Ketamine elicits rapid antidepressant and alleviates anhedonia in MDD. To clarify how ketamine perturbs reward circuitry in MDD, we examined how serial ketamine infusions (SKI) modulate static and dynamic functional connectivity (FC) in Hb and NAc networks.

White matter microstructural perturbations after total sleep deprivation in depression.

Background: Total sleep deprivation (TSD) transiently reverses depressive symptoms in a majority of patients with depression. How TSD modulates diffusion tensor imaging (DTI) measures of white matter (WM) microstructure, which may be linked with TSD's rapid antidepressant effects, remains uncharacterized.

Methods: Patients with depression ( = 48, mean age = 33, 26 women) completed diffusion-weighted imaging and Hamilton Depression Rating (HDRS) and rumination scales before and after >24 h of TSD.

Advances in Nucleotide Repeat Expansion Diseases: Transcription Gets in Phase.

Unstable DNA repeat expansions and insertions have been found to cause more than 50 neurodevelopmental, neurodegenerative, and neuromuscular disorders. One of the main hallmarks of repeat expansion diseases is the formation of abnormal RNA or protein aggregates in the neuronal cells of affected individuals. Recent evidence indicates that alterations of the dynamic or material properties of biomolecular condensates assembled by liquid/liquid phase separation are critical for the formation of these aggregates.

Molecular Mechanisms in Pentanucleotide Repeat Diseases.

The number of neurodegenerative diseases resulting from repeat expansion has increased extraordinarily in recent years. In several of these pathologies, the repeat can be transcribed in RNA from both DNA strands producing, at least, one toxic RNA repeat that causes neurodegeneration by a complex mechanism. Recently, seven diseases have been found caused by a novel intronic pentanucleotide repeat in distinct genes encoding proteins highly expressed in the cerebellum.

Modulation of the functional connectome in major depressive disorder by ketamine therapy.

Background: Subanesthetic ketamine infusion therapy can produce fast-acting antidepressant effects in patients with major depression. How single and repeated ketamine treatment modulates the whole-brain functional connectome to affect clinical outcomes remains uncharacterized.

Methods: Data-driven whole brain functional connectivity (FC) analysis was used to identify the functional connections modified by ketamine treatment in patients with major depressive disorder (MDD).

Antisense Transcription across Nucleotide Repeat Expansions in Neurodegenerative and Neuromuscular Diseases: Progress and Mysteries.

Unstable repeat expansions and insertions cause more than 30 neurodegenerative and neuromuscular diseases. Remarkably, bidirectional transcription of repeat expansions has been identified in at least 14 of these diseases. More remarkably, a growing number of studies has been showing that both sense and antisense repeat RNAs are able to dysregulate important cellular pathways, contributing together to the observed clinical phenotype.

Modulation of inhibitory control networks relate to clinical response following ketamine therapy in major depression.

Subanesthetic ketamine is found to induce fast-acting and pronounced antidepressant effects, even in treatment resistant depression (TRD). However, it remains unclear how ketamine modulates neural function at the brain systems-level to regulate emotion and behavior. Here, we examined treatment-related changes in the inhibitory control network after single and repeated ketamine therapy in TRD.

Mutational mechanism for DAB1 (ATTTC) insertion in SCA37: ATTTT repeat lengthening and nucleotide substitution.

Dynamic mutations by microsatellite instability are the molecular basis of a growing number of neuromuscular and neurodegenerative diseases. Repetitive stretches in the human genome may drive pathogenicity, either by expansion above a given threshold, or by insertion of abnormal tracts in nonpathogenic polymorphic repetitive regions, as is the case in spinocerebellar ataxia type 37 (SCA37). We have recently established that this neurodegenerative disease is caused by an (ATTTC) insertion within an (ATTTT) in a noncoding region of DAB1.

A repeat-primed PCR assay for pentanucleotide repeat alleles in spinocerebellar ataxia type 37.

Spinocerebellar ataxia 37 (SCA37) is caused by an (ATTTC) insertion in a polymorphic ATTTT repeat in the non-coding region of DAB1. The non-pathogenic alleles have a configuration [(ATTTT)], whereas pathogenic alleles have a complex structure of [(ATTTT)(ATTTC)(ATTTT)]. Molecular diagnosis of SCA37 is laborious because about 7% of the pentanucleotide repeat alleles in DAB1 are larger than 30 units and, thus, fail to amplify with standard PCR conditions, resulting in apparently homoallelism or in complete lack of PCR amplification in several cases.

In-vivo quantitative structural imaging of the human midbrain and the superior colliculus at 9.4T.

We explored anatomical details of the superior colliculus (SC) by in vivo magnetic resonance imaging (MRI) at 9.4T. The high signal-to-noise ratio allowed the acquisition of high resolution, multi-modal images with voxel sizes ranging between 176 × 132 × 600 μm and (800)μm.

A Pentanucleotide ATTTC Repeat Insertion in the Non-coding Region of DAB1, Mapping to SCA37, Causes Spinocerebellar Ataxia.

Advances in human genetics in recent years have largely been driven by next-generation sequencing (NGS); however, the discovery of disease-related gene mutations has been biased toward the exome because the large and very repetitive regions that characterize the non-coding genome remain difficult to reach by that technology. For autosomal-dominant spinocerebellar ataxias (SCAs), 28 genes have been identified, but only five SCAs originate from non-coding mutations. Over half of SCA-affected families, however, remain without a genetic diagnosis.

Contraction of fully expanded FMR1 alleles to the normal range: predisposing haplotype or rare events?

Fragile X syndrome (FXS), the most common cause of inherited intellectual disability, is due to the expansion over 200 CGGs and methylation of this polymorphic region, in the 5'-UTR (untranslated region) of FMR1 (Xq27.3). We have identified four FXS mosaic males: M1-(CGG)/(CGG); M2-(CGG)/(CGG); M3-(CGG)/(CGG); and M4-(CGG)/(CGG)/(CGG).

Depth-dependence of visual signals in the human superior colliculus at 9.4 T.

The superior colliculus (SC) is a layered structure located in the midbrain. We exploited the improved spatial resolution and BOLD signal strength available at 9.4 T to investigate the depth profile of visual BOLD responses in the human SC based on distortion-corrected EPI data with a 1 mm isotropic resolution.

Unstable repeat expansions in neurodegenerative diseases: nucleocytoplasmic transport emerges on the scene.

An astonishing number of neurological diseases result from expansion of unstable repetitive sequences causing alterations in key neuronal processes. Some are progressive late-onset conditions related to aging, such as the spinocerebellar ataxias. In several of these pathologies, the expanded repeat is transcribed, producing an expanded RNA repeat that causes neurodegeneration by a complex mechanism, comprising 3 main pathways.