We sought to determine if Parkinson's disease (PD) with mild cognitive impairment (MCI) is associated with a greater SERIAL-ORDER (mental manipulation) than ANY-ORDER (auditory span, storage) deficit in working memory (WM). We investigated WM combining neuropsychological measures with the study of brain functional connectivity. A cohort of 160 patients with idiopathic PD, classified as PD-MCI (n = 87) or PD with normal cognition (PD-NC; n = 73), and 70 matched healthy controls were studied. Verbal WM was assessed with the Backward Digit Span Task (BDT; Lamar et al., 2007, Neuropsychologia, 45, 245), measuring SERIAL-ORDER and ANY-ORDER recall. Resting-state MRI data were collected for 15 PD-MCI, 15 PD-NC and 30 controls. Hypothesis-driven seed-based functional connectivity of the dorsolateral prefrontal cortex (DLPFC) was compared between the three groups and correlated with BDT performance. We found the main effect of the test (impairment in SERIAL ORDER > ANY ORDER) and group ((NC = PD-NC) > PD-MCI) in BDT performance that was even more pronounced in SERIAL ORDER when controlling for ANY ORDER variability but not vice versa. Furthermore, PD-MCI compared to other groups were characterized by the functional disconnection between the bilateral DLPFC and the cerebellum. In functional correlations, DLPFC connectivity was positively related to both SERIAL- and ANY-ORDER performance. In conclusion, PD-MCI patients evidenced greater SERIAL-ORDER (manipulation and cognitive control) than ANY-ORDER (storage) working memory impairment than PD-NC and controls with a disrupted DLPFC resting-state connectivity that was also related to the verbal WM performance.

• Klíčová slova
• Backward Digit Span Task, Parkinson’s disease, SERIAL ORDER, mild cognitive impairment, working memory,
• MeSH
• kognice MeSH
• kognitivní dysfunkce * diagnostické zobrazování   etiologie   MeSH
• krátkodobá paměť MeSH
• lidé MeSH
• neuropsychologické testy MeSH
• neurozobrazování MeSH
• Parkinsonova nemoc * komplikace   diagnostické zobrazování   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Direct electrical stimulation of the human brain can elicit sensory and motor perceptions as well as recall of memories. Stimulating higher order association areas of the lateral temporal cortex in particular was reported to activate visual and auditory memory representations of past experiences (Penfield and Perot, 1963). We hypothesized that this effect could be used to modulate memory processing. Recent attempts at memory enhancement in the human brain have been focused on the hippocampus and other mesial temporal lobe structures, with a few reports of memory improvement in small studies of individual brain regions. Here, we investigated the effect of stimulation in four brain regions known to support declarative memory: hippocampus, parahippocampal neocortex, prefrontal cortex and temporal cortex. Intracranial electrode recordings with stimulation were used to assess verbal memory performance in a group of 22 patients (nine males). We show enhanced performance with electrical stimulation in the lateral temporal cortex (paired t-test, P = 0.0067), but not in the other brain regions tested. This selective enhancement was observed both on the group level, and for two of the four individual subjects stimulated in the temporal cortex. This study shows that electrical stimulation in specific brain areas can enhance verbal memory performance in humans.awx373media15704855796001.

• MeSH
• časové faktory MeSH
• dospělí MeSH
• epilepsie komplikace   MeSH
• hluboká mozková stimulace metody   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mapování mozku MeSH
• mladý dospělý MeSH
• poruchy paměti etiologie   terapie   MeSH
• spánkový lalok fyziologie   MeSH
• verbální učení fyziologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• audiovizuální média MeSH
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH

Copper is an important trace element that is required for essential enzymes. However, due to its redox activity, copper can also lead to the generation of toxic reactive oxygen species. Therefore, cellular uptake, storage as well as export of copper have to be tightly regulated in order to guarantee sufficient copper supply for the synthesis of copper-containing enzymes but also to prevent copper-induced oxidative stress. In brain, copper is of importance for normal development. In addition, both copper deficiency as well as excess of copper can seriously affect brain functions. Therefore, this organ possesses ample mechanisms to regulate its copper metabolism. In brain, astrocytes are considered as important regulators of copper homeostasis. Impairments of homeostatic mechanisms in brain copper metabolism have been associated with neurodegeneration in human disorders such as Menkes disease, Wilson's disease and Alzheimer's disease. This review article will summarize the biological functions of copper in the brain and will describe the current knowledge on the mechanisms involved in copper transport, storage and export of brain cells. The role of copper in diseases that have been connected with disturbances in brain copper homeostasis will also be discussed.

• Klíčová slova
• Astrocytes, Brain, Copper, Neurodegeneration, Transport,
• MeSH
• astrocyty fyziologie   MeSH
• homeostáza MeSH
• lidé MeSH
• měď metabolismus   MeSH
• mozek fyziologie   patofyziologie   MeSH
• neurodegenerativní nemoci patofyziologie   MeSH
• neurony fyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• měď MeSH

INTRODUCTION: Severe traumatic brain injury belongs to diagnoses with unfavourable outcome. Almost half of patients die due to this diagnose and many survivals remain severely disabled. MATERIAL AND METHODS: In our follow-up file we evaluated 52 patients treated at neurosurgical department due to this diagnosis. The survivals were subsequently examined in order to determine the severity of their objective neurological and cognitive problems. RESULTS: Mortality rate in our group reached 56 %. The overall results show cognitive disorders (memory disorders, prolonged latency and concentration disorders). Out of 92 % of surviving patients, it was neurological impairment that was most frequently (65 %) involved. CONCLUSION: Both cognitive disorders and neurological impairments are responsible for complicated resocialising including working ability which is very low after severe traumatic brain injury--in our group 26 %. Major obstacle can be seen in the psychological component of their over-all impaired quality of life (Tab. 5, Ref. 6).

• MeSH
• dospělí MeSH
• Glasgowská stupnice následků MeSH
• kognitivní poruchy etiologie   MeSH
• kvalita života MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• nemoci nervového systému etiologie   MeSH
• obnova funkce MeSH
• poranění mozku komplikace   terapie   MeSH
• senioři MeSH
• zaměstnanost * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Although the cerebellum contributes to higher-order cognitive and emotional functions relevant to posttraumatic stress disorder (PTSD), prior research on cerebellar volume in PTSD is scant, particularly when considering subregions that differentially map on to motor, cognitive, and affective functions. In a sample of 4215 adults (PTSD n = 1642; Control n = 2573) across 40 sites from the ENIGMA-PGC PTSD working group, we employed a new state-of-the-art deep-learning based approach for automatic cerebellar parcellation to obtain volumetric estimates for the total cerebellum and 28 subregions. Linear mixed effects models controlling for age, gender, intracranial volume, and site were used to compare cerebellum volumes in PTSD compared to healthy controls (88% trauma-exposed). PTSD was associated with significant grey and white matter reductions of the cerebellum. Compared to controls, people with PTSD demonstrated smaller total cerebellum volume, as well as reduced volume in subregions primarily within the posterior lobe (lobule VIIB, crus II), vermis (VI, VIII), flocculonodular lobe (lobule X), and corpus medullare (all p-FDR < 0.05). Effects of PTSD on volume were consistent, and generally more robust, when examining symptom severity rather than diagnostic status. These findings implicate regionally specific cerebellar volumetric differences in the pathophysiology of PTSD. The cerebellum appears to play an important role in higher-order cognitive and emotional processes, far beyond its historical association with vestibulomotor function. Further examination of the cerebellum in trauma-related psychopathology will help to clarify how cerebellar structure and function may disrupt cognitive and affective processes at the center of translational models for PTSD.

• MeSH
• bílá hmota patologie   diagnostické zobrazování   MeSH
• deep learning MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie * metody   MeSH
• mozeček * patologie   diagnostické zobrazování   MeSH
• posttraumatická stresová porucha * patologie   patofyziologie   diagnostické zobrazování   MeSH
• šedá hmota patologie   MeSH
• velikost orgánu MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH

ADHD is a common chronic neurodevelopmental disorder and is characterized by persistent inattention, hyperactivity, impulsivity and are often accompanied by learning and memory impairment. Great evidence has shown that learning and memory impairment of ADHD plays an important role in its executive function deficits, which seriously affects the development of academic, cognitive and daily social skills and will cause a serious burden on families and society. With the increasing attention paid to learning and memory impairment in ADHD, relevant research is gradually increasing. In this article, we will present the current research results of learning and memory impairment in ADHD from the following aspects. Firstly, the animal models of ADHD, which display the core symptoms of ADHD as well as with learning and memory impairment. Secondly, the molecular mechanism of has explored, including some neurotransmitters, receptors, RNAs, etc. Thirdly, the susceptibility gene of ADHD related to the learning and impairment in order to have a more comprehensive understanding of the pathogenesis. Key words: Learning and memory, ADHD, Review.

• MeSH
• hyperkinetická porucha * psychologie   genetika   MeSH
• lidé MeSH
• modely nemocí na zvířatech MeSH
• paměť MeSH
• poruchy paměti * psychologie   etiologie   MeSH
• poruchy učení psychologie   etiologie   MeSH
• učení MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Inherited monoamine neurotransmitter disorders (iMNDs) are rare disorders with clinical manifestations ranging from mild infantile hypotonia, movement disorders to early infantile severe encephalopathy. Neuroimaging has been reported as non-specific. We systematically analyzed brain MRIs in order to characterize and better understand neuroimaging changes and to re-evaluate the diagnostic role of brain MRI in iMNDs. 81 MRIs of 70 patients (0.1-52.9 years, 39 patients with tetrahydrobiopterin deficiencies, 31 with primary disorders of monoamine metabolism) were retrospectively analyzed and clinical records reviewed. 33/70 patients had MRI changes, most commonly atrophy (n = 24). Eight patients, six with dihydropteridine reductase deficiency (DHPR), had a common pattern of bilateral parieto-occipital and to a lesser extent frontal and/or cerebellar changes in arterial watershed zones. Two patients imaged after acute severe encephalopathy had signs of profound hypoxic-ischemic injury and a combination of deep gray matter and watershed injury (aromatic l-amino acid decarboxylase (AADCD), tyrosine hydroxylase deficiency (THD)). Four patients had myelination delay (AADCD; THD); two had changes characteristic of post-infantile onset neuronal disease (AADCD, monoamine oxidase A deficiency), and nine T2-hyperintensity of central tegmental tracts. iMNDs are associated with MRI patterns consistent with chronic effects of a neuronal disorder and signs of repetitive injury to cerebral and cerebellar watershed areas, in particular in DHPRD. These will be helpful in the (neuroradiological) differential diagnosis of children with unknown disorders and monitoring of iMNDs. We hypothesize that deficiency of catecholamines and/or tetrahydrobiopterin increase the incidence of and the CNS susceptibility to vascular dysfunction.

• Klíčová slova
• MRI, inherited neurotransmitter disorders, monoamines, tetrahydrobiopterin deficiency, watershed injury,
• MeSH
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie * MeSH
• mapování mozku metody   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mozek diagnostické zobrazování   patologie   MeSH
• předškolní dítě MeSH
• retrospektivní studie MeSH
• vrozené poruchy metabolismu aminokyselin diagnostické zobrazování   patologie   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: Bipolar disorder (BD) is a common and highly heritable disorder of mood. Genome-wide association studies (GWAS) have identified several independent susceptibility loci. In order to extract more biological information from GWAS data, multi-locus approaches represent powerful tools since they utilize knowledge about biological processes to integrate functional sets of genes at strongly to moderately associated loci. METHODS: We conducted gene set enrichment analyses (GSEA) using 2.3 million single-nucleotide polymorphisms, 397 Reactome pathways and 24,025 patients with BD and controls. RNA expression of implicated individual genes and gene sets were examined in post-mortem brains across lifespan. RESULTS: Two pathways showed a significant enrichment after correction for multiple comparisons in the GSEA: GRB2 events in ERBB2 signaling, for which 6 of 21 genes were BD associated (PFDR = 0.0377), and NCAM signaling for neurite out-growth, for which 11 out of 62 genes were BD associated (PFDR = 0.0451). Most pathway genes showed peaks of RNA co-expression during fetal development and infancy and mapped to neocortical areas and parts of the limbic system. LIMITATIONS: Pathway associations were technically reproduced by two methods, although they were not formally replicated in independent samples. Gene expression was explored in controls but not in patients. CONCLUSIONS: Pathway analysis in large GWAS data of BD and follow-up of gene expression patterns in healthy brains provide support for an involvement of neurodevelopmental processes in the etiology of this neuropsychiatric disease. Future studies are required to further evaluate the relevance of the implicated genes on pathway functioning and clinical aspects of BD.

• Klíčová slova
• Bipolar disorder, GRB2 events in ERBB2 signaling, NCAM signaling for neurite out-growth, Neurodevelopmental disorder, Pathway analysis,
• MeSH
• adaptorový protein Grb2 genetika   metabolismus   MeSH
• algoritmy MeSH
• bipolární porucha genetika   metabolismus   patofyziologie   MeSH
• celogenomová asociační studie MeSH
• exprese genu MeSH
• fenotyp MeSH
• genetická predispozice k nemoci MeSH
• geny erbB-2 fyziologie   MeSH
• jednonukleotidový polymorfismus MeSH
• lidé MeSH
• mozek růst a vývoj   metabolismus   MeSH
• receptor erbB-2 metabolismus   MeSH
• RNA metabolismus   MeSH
• signální transdukce * MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• adaptorový protein Grb2 MeSH
• GRB2 protein, human MeSH Prohlížeč
• receptor erbB-2 MeSH
• RNA MeSH

INTRODUCTION: Deep brain stimulation (DBS) of the internal globus pallidus (GPi) is a well-established, effective treatment for dystonia. Substantial variability of therapeutic success has been the one of the drivers of an ongoing debate about proper stimulation site and settings, with several indications of the notional sweet spot pointing to the lower GPi or even subpallidal area. METHODS: The presented patient-blinded, random-order study with cross-sectional verification against healthy controls enrolled 17 GPi DBS idiopathic, cervical or generalised dystonia patients to compare the effect of the stimulation in the upper and lower GPi area, with the focus on sensorimotor network connectivity and local activity measured using functional magnetic resonance. RESULTS: Stimulation brought both these parameters to levels closer to the state detected in healthy controls. This effect was much more pronounced during the stimulation in the lower GPi area or beneath it than in slightly higher positions, with stimulation-related changes detected by both metrics of interest in the sensorimotor cortex, striatum, thalamus and cerebellum. CONCLUSIONS: All in all, this study not only replicated the results of previous studies on GPi DBS as a modality restoring sensorimotor network connectivity and local activity in dystonia towards the levels in healthy population, but also showed that lower GPi area or even subpallidal structures, be it white matter or even small, but essential nodes in the zona incerta as nucleus basalis of Meynert, are important regions to consider when programming DBS in dystonia patients.

• Klíčová slova
• Deep brain stimulation, Dystonia, Internal globus pallidus, Resting-state functional magnetic resonance imaging,
• MeSH
• dospělí MeSH
• dystonické poruchy * terapie   diagnostické zobrazování   patofyziologie   MeSH
• dystonie * terapie   diagnostické zobrazování   patofyziologie   MeSH
• globus pallidus * diagnostické zobrazování   patofyziologie   MeSH
• hluboká mozková stimulace * metody   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie metody   MeSH
• průřezové studie MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Glymphatic system is an emerging pathway of removing metabolic waste products and toxic solutes from the brain tissue. It is made of a network of perivascular spaces, filled in cerebrospinal and interstitial fluid, encompassing penetrating and pial vessels and communicating with the subarachnoid space. It is separated from vessels by the blood brain barrier and from brain tissue by the endfeet of the astrocytes rich in aquaporin 4, a membrane protein which controls the water flow along the perivascular space. Animal models and magnetic resonance (MR) studies allowed to characterize the glymphatic system function and determine how its impairment could lead to numerous neurological disorders (e.g. Alzheimer's disease, stroke, sleep disturbances, migraine, idiopathic normal pressure hydrocephalus). This review aims to summarize the role of the glymphatic system in the pathophysiology of migraine in order to provide new ways of approaching to this disease and to its therapy.

• Klíčová slova
• CGRP, Cerebrospinal fluid, Cortical spreading depression, DTI-ALPS, Glymphatic system, Headache, Migraine, Neurological disorders, Perivascular space,
• MeSH
• bolesti hlavy metabolismus   MeSH
• glymfatický systém * diagnostické zobrazování   metabolismus   MeSH
• hematoencefalická bariéra metabolismus   MeSH
• migréna * diagnostické zobrazování   metabolismus   MeSH
• mozek diagnostické zobrazování   metabolismus   MeSH
• nemoci nervového systému * metabolismus   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH