Enhancing reward learning in the absence of an effect on reward
This scientific commentary refers to ‘Impulse control disorder in Parkinson’s disease is associated with abnormal frontal value signalling’ by Tichelaaret al. (https://doi.org/10.1093/brain/awad162). (Source: Brain)
Source: Brain - July 20, 2023 Category: Neurology Source Type: research
Same, same … but different!
This scientific commentary refers to ‘Severe cholinergic terminal loss in newly diagnosed dementia with Lewy bodies’ by Okkelset al. (https://doi.org/10.1093/brain/awad192). (Source: Brain)
Source: Brain - July 15, 2023 Category: Neurology Source Type: research
Addressing the gaps between socioeconomic disparities and biological models of dementia
(Source: Brain)
Source: Brain - July 12, 2023 Category: Neurology Source Type: research
Transactive response DNA-binding protein 43 is enriched at the centrosome in human cells
AbstractThe centrosome, as the main microtubule organizing centre, plays key roles in cell polarity, genome stability and ciliogenesis. The recent identification of ribosomes, RNA-binding proteins and transcripts at the centrosome suggests local protein synthesis. In this context, we hypothesized that TDP-43, a highly conserved RNA binding protein involved in the pathophysiology of amyotrophic lateral sclerosis and frontotemporal lobar degeneration, could be enriched at this organelle. Using dedicated high magnification sub-diffraction microscopy on human cells, we discovered a novel localization of TDP-43 at the centrosom...
Source: Brain - July 6, 2023 Category: Neurology Source Type: research
Corticostriatal beta oscillation changes associated with cognitive function in Parkinson ’s disease
The objective of our study is to evaluate whether changes in beta oscillations in the caudate and DLPFC contribute to cognitive impairment in Parkinson’s disease patients. To investigate this, we used local field potential recordings during deep brain stimulation surgery in 15 patients with Parkinson’s disease. Local field potentials were recorded from DLPFC and caudate at rest and during a working memory task. We examined changes in beta oscillatory power during the working memory task as well as t he relationship of beta oscillatory activity to preoperative cognitive status, as determined from neuropsychological test...
Source: Brain - June 16, 2023 Category: Neurology Source Type: research
Severe cholinergic terminal loss in newly diagnosed dementia with Lewy bodies
In conclusion, this study provides robust evidence for severe cholinergic terminal loss in newly diagnosed dementia with Lewy bodies, which correlates with structural imaging measures of cholinergic basal forebrain degeneration. In patients without dementia, our findings suggest that loss of cholinergic terminal function occurs ‘before’ neuronal cell degeneration. Moreover, the study supports that degeneration of the cholinergic system is important for brain metabolism and may be linked with degeneration in other transmitter systems. Our findings have implications for understanding how cholinergic system pathology cont...
Source: Brain - June 5, 2023 Category: Neurology Source Type: research
The functional role of the precuneus
AbstractRecent advancements in computational approaches and neuroimaging techniques have refined our understanding of the precuneus. While previously believed to be largely a visual processing region, the importance of the precuneus in complex cognitive functions has been previously less familiar due to a lack of focal lesions in this deeply seated region, but also a poor understanding of its true underlying anatomy. Fortunately, recent studies have revealed significant information on the structural and functional connectivity of this region, and this data has provided a more detailed mechanistic understanding of the impor...
Source: Brain - May 31, 2023 Category: Neurology Source Type: research
Rare variants in ANO1, encoding a calcium-activated chloride channel, predispose to moyamoya disease
AbstractMoyamoya disease, a cerebrovascular disease leading to strokes in children and young adults, is characterized by progressive occlusion of the distal internal carotid arteries and the formation of collateral vessels. Altered genes play a prominent role in the aetiology of moyamoya disease, but a causative gene is not identified in the majority of cases.Exome sequencing data from 151 individuals from 84 unsolved families were analysed to identify further genes for moyamoya disease, then candidate genes assessed in additional cases (150 probands). Two families had the same rare variant inANO1, which encodes a calcium-...
Source: Brain - May 30, 2023 Category: Neurology Source Type: research
Molecular basis of FAAH-OUT-associated human pain insensitivity
AbstractChronic pain affects millions of people worldwide and new treatments are needed urgently. One way to identify novel analgesic strategies is to understand the biological dysfunctions that lead to human inherited pain insensitivity disorders. Here we report how the recently discovered brain and dorsal root ganglia-expressedFAAH-OUT long non-coding RNA (lncRNA) gene, which was found from studying a pain-insensitive patient with reduced anxiety and fast wound healing, regulates the adjacent key endocannabinoid system geneFAAH, which encodes the anandamide-degrading fatty acid amide hydrolase enzyme.We demonstrate that ...
Source: Brain - May 24, 2023 Category: Neurology Source Type: research
Cerebrospinal fluid transcripts may predict shunt surgery responses in normal pressure hydrocephalus
We describe a machine learning algorithm trained on these gene expression profiles to predict shunt surgery response with high accuracy. The transcriptomic signatures we identified may have important implications for improving NPH diagnosis and treatment and for understanding disease aetiology. (Source: Brain)
Source: Brain - May 19, 2023 Category: Neurology Source Type: research
Disease, disorder, condition or enigma? Epilepsy and its modern history re-examined
(Source: Brain)
Source: Brain - May 19, 2023 Category: Neurology Source Type: research
Impulse control disorder in Parkinson ’s disease is associated with abnormal frontal value signalling
AbstractDopaminergic medication is well established to boost reward- versus punishment-based learning in Parkinson ’s disease. However, there is tremendous variability in dopaminergic medication effects across different individuals, with some patients exhibiting much greater cognitive sensitivity to medication than others. We aimed to unravel the mechanisms underlying this individual variability in a large het erogeneous sample of early-stage patients with Parkinson’s disease as a function of comorbid neuropsychiatric symptomatology, in particular impulse control disorders and depression.One hundred and ninety-nine pat...
Source: Brain - May 16, 2023 Category: Neurology Source Type: research
Advances in understanding the function of alpha-synuclein: implications for Parkinson ’s disease
AbstractThe critical role of alpha-synuclein in Parkinson ’s disease represents a pivotal discovery. Some progress has been made over recent years in identifying disease-modifying therapies for Parkinson’s disease that target alpha-synuclein. However, these treatments have not yet shown clear efficacy in slowing the progression of this disease. Several explanations exist for this issue. The pathogenesis of Parkinson’s disease is complex and not yet fully clarified and the heterogeneity of the disease, with diverse genetic susceptibility and risk factors and different clinical courses, adds further complexity. Thus, a...
Source: Brain - May 15, 2023 Category: Neurology Source Type: research
TGF β4 alleviates the phenotype of Charcot–Marie–Tooth disease type 1A
AbstractThe duplication of the peripheral myelin protein 22 (PMP22) gene causes a demyelinating type of neuropathy, commonly known as Charcot –Marie–Tooth disease type 1A (CMT1A). Development of effective drugs for CMT1A still remains as an unmet medical need.In the present study, we assessed the role of the transforming growth factor beta 4 (TGFβ4)/Nodal axis in the pathogenesis of CMT1A.First, we identified PMP22 overexpression-ind uced Nodal expression in Schwann cells, which might be one of the downstream effectors in CMT1A. Administration of Nodal protein at the developmental stage of peripheral nerves induced th...
Source: Brain - May 5, 2023 Category: Neurology Source Type: research
Cortical microstructural gradients capture memory network reorganization in temporal lobe epilepsy
AbstractTemporal lobe epilepsy (TLE), one of the most common pharmaco-resistant epilepsies, is associated with pathology of paralimbic brain regions, particularly in the mesiotemporal lobe. Cognitive dysfunction in TLE is frequent, and particularly affects episodic memory. Crucially, these difficulties challenge the quality of life of patients, sometimes more than seizures, underscoring the need to assess neural processes of cognitive dysfunction in TLE to improve patient management.Our work harnessed a novel conceptual and analytical approach to assess spatial gradients of microstructural differentiation between cortical ...
Source: Brain - April 21, 2023 Category: Neurology Source Type: research
