Strategic white matter hyperintensity locations associated with post-stroke cognitive impairment: A multicenter study in 1568 stroke patients.

Background: Post-stroke cognitive impairment (PSCI) occurs in up to 50% of stroke survivors. Presence of pre-existing vascular brain injury, in particular the extent of white matter hyperintensities (WMH), is associated with worse cognitive outcome after stroke, but the role of WMH location in this association is unclear.

Aims: We determined if WMH in strategic white matter tracts explain cognitive performance after stroke.

Cerebellar-Induced Aphasia After Stroke: Evidence for the "Linguistic Cerebellum".

The cerebellum is traditionally known to subserve motor functions. However, for several decades, the concept of the "cerebellar cognitive affective syndrome" has evolved. Studies in healthy participants and patients have confirmed the cerebellar role in language.

The CODECS study: COgnitive DEficits in Cerebellar Stroke.

Part of the extra-pyramidal system, the cerebellum is more and more recognized by its non-motor functions known as the cerebellar cognitive affective syndrome. Several studies have identified disturbances specifically in executive and attentional functions after focal cerebellar lesions. However, most studies were performed in small and heterogeneous patient groups.

White Matter Hyperintensity Volume and Poststroke Cognition: An Individual Patient Data Pooled Analysis of 9 Ischemic Stroke Cohort Studies.

Background: White matter hyperintensities (WMH) are associated with cognitive dysfunction after ischemic stroke. Yet, uncertainty remains about affected domains, the role of other preexisting brain injury, and infarct types in the relation between WMH burden and poststroke cognition. We aimed to disentangle these factors in a large sample of patients with ischemic stroke from different cohorts.

Network impact score is an independent predictor of post-stroke cognitive impairment: A multicenter cohort study in 2341 patients with acute ischemic stroke.

Background: Post-stroke cognitive impairment (PSCI) is a common consequence of stroke. Accurate prediction of PSCI risk is challenging. The recently developed network impact score, which integrates information on infarct location and size with brain network topology, may improve PSCI risk prediction.

Strategic infarct locations for post-stroke cognitive impairment: a pooled analysis of individual patient data from 12 acute ischaemic stroke cohorts.

Background: Post-stroke cognitive impairment (PSCI) occurs in approximately half of people in the first year after stroke. Infarct location is a potential determinant of PSCI, but a comprehensive map of strategic infarct locations predictive of PSCI is unavailable. We aimed to identify infarct locations most strongly predictive of PSCI after acute ischaemic stroke and use this information to develop a prediction model.

The Meta VCI Map consortium for meta-analyses on strategic lesion locations for vascular cognitive impairment using lesion-symptom mapping: Design and multicenter pilot study.

Introduction: The Meta VCI Map consortium performs meta-analyses on strategic lesion locations for vascular cognitive impairment using lesion-symptom mapping. Integration of data from different cohorts will increase sample sizes, to improve brain lesion coverage and support comprehensive lesion-symptom mapping studies.

Methods: Cohorts with available imaging on white matter hyperintensities or infarcts and cognitive testing were invited.

Modulation of Murine Olivary Connexin 36 Gap Junctions by PKA and CaMKII.

The inferior olive (IO) is a nucleus located in the brainstem and it is part of the olivo-cerebellar loop. This circuit plays a fundamental role in generation and acquisition of coherent motor patterns and it relies on synchronous activation of groups of Purkinje cells (PC) in the cerebellar cortex. IO neurons integrate their intrinsic oscillatory activity with excitatory inputs coming from the somatosensory system and inhibitory feedback coming from the cerebellar nuclei.

Positive remodeling at 3 year follow up is associated with plaque-free coronary wall segment at baseline: a serial IVUS study.

Aims: At present it is unknown what limits the arterial remodeling process during atherosclerotic plaque formation. In healthy arteries remodeling is regulated by the shear stress induced response by the endothelium. As endothelium at the plaque site is assumed to be dysfunctional, we tested the hypothesis that plaque free wall (PFW) determines vascular remodeling during atherosclerotic plaque build-up.

Olivary subthreshold oscillations and burst activity revisited.

The inferior olive (IO) forms one of the major gateways for information that travels to the cerebellar cortex. Olivary neurons process sensory and motor signals that are subsequently relayed to Purkinje cells. The intrinsic subthreshold membrane potential oscillations of the olivary neurons are thought to be important for gating this flow of information.

The effectiveness of graded activity in patients with non-specific low-back pain: a systematic review.

Background: Non-specific low-back pain (LBP) is considered a major health and economic problem in Western society. Nowadays a common used intervention on non-specific LBP is graded activity (GA). Graded Activity developed by Lindström et al.

Anti-malaria drug mefloquine induces motor learning deficits in humans.

Mefloquine (a marketed anti-malaria drug) prophylaxis has a high risk of causing adverse events. Interestingly, animal studies have shown that mefloquine imposes a major deficit in motor learning skills by affecting the connexin 36 gap junctions of the inferior olive. We were therefore interested in assessing whether mefloquine might induce similar effects in humans.

Role of olivary electrical coupling in cerebellar motor learning.

The level of electrotonic coupling in the inferior olive is extremely high, but its functional role in cerebellar motor control remains elusive. Here, we subjected mice that lack olivary coupling to paradigms that require learning-dependent timing. Cx36-deficient mice showed impaired timing of both locomotion and eye-blink responses that were conditioned to a tone.

In vivo mouse inferior olive neurons exhibit heterogeneous subthreshold oscillations and spiking patterns.

In vitro whole-cell recordings of the inferior olive have demonstrated that its neurons are electrotonically coupled and have a tendency to oscillate. However, it remains to be shown to what extent subthreshold oscillations do indeed occur in the inferior olive in vivo and whether its spatiotemporal firing pattern may be dynamically generated by including or excluding different types of oscillatory neurons. Here, we did whole-cell recordings of olivary neurons in vivo to investigate the relation between their subthreshold activities and their spiking behavior in an intact brain.

Altered olivocerebellar activity patterns in the connexin36 knockout mouse.

The inferior olive (IO) has among the highest densities of neuronal gap junctions in the nervous system. These gap junctions are proposed to be the underlying mechanism for generating synchronous Purkinje cell complex spike (CS) activity. Gap junctions between neurons are formed mostly by connexin36 proteins.

Contribution of CYLN2 and GTF2IRD1 to neurological and cognitive symptoms in Williams Syndrome.

Williams Syndrome (WS, [MIM 194050]) is a disorder caused by a hemizygous deletion of 25-30 genes on chromosome 7q11.23. Several of these genes including those encoding cytoplasmic linker protein-115 (CYLN2) and general transcription factors (GTF2I and GTF2IRD1) are expressed in the brain and may contribute to the distinct neurological and cognitive deficits in WS patients.

Spatiotemporal distribution of Connexin45 in the olivocerebellar system.

The olivocerebellar system is involved in the transmission of information to maintain sensory motor coordination. Gap junctions have been described in various types of neurons in this system, including the neurons in the inferior olive that provide the climbing fibers to Purkinje cells. While it is well established that Connexin36 is necessary for the formation of these neuronal gap junctions, it is not clear whether these electrical synapses can develop without Connexin45.

GATA3 haploinsufficiency causes a rapid deterioration of distortion product otoacoustic emissions (DPOAEs) in mice.

Human HDR (hypoparathyroidism, deafness and renal dysplasia)-syndrome is caused by haploinsufficiency of zinc-finger transcription factor GATA3. The hearing loss due to GATA3 haploinsufficiency has been shown to be peripheral in origin, but it is unclear to what extent potential aberrations in the outer hair cells (OHCs) contribute to this disorder. To further elucidate the pathophysiological mechanism underlying the hearing defect in HDR-syndrome, we investigated the OHCs in heterozygous Gata3-knockout mice at both the functional and morphological level.

Mucuna pruriens in Parkinson's disease: a double blind clinical and pharmacological study.

Background: The seed powder of the leguminous plant, Mucuna pruriens has long been used in traditional Ayurvedic Indian medicine for diseases including parkinsonism. We have assessed the clinical effects and levodopa (L-dopa) pharmacokinetics following two different doses of mucuna preparation and compared them with standard L-dopa/carbidopa (LD/CD).

Methods: Eight Parkinson's disease patients with a short duration L-dopa response and on period dyskinesias completed a randomised, controlled, double blind crossover trial.

Expression pattern of lacZ reporter gene representing connexin36 in transgenic mice.

Targeted deletion of the connexin36 (Cx36) gene in the mouse genome leads to visual transmission defects, weakened synchrony of rhythmic inhibitory potentials in the neocortex, and disruption of gamma-frequency network oscillations. We have generated transgenic mice in which a reporter protein consisting of the exon1 coded N-terminal part of Cx36 fused to beta-galactosidase (N36-beta-gal) is expressed instead of Cx36. Here, we have used these mice for a detailed analysis of the reporter gene expression.

Deformation of network connectivity in the inferior olive of connexin 36-deficient mice is compensated by morphological and electrophysiological changes at the single neuron level.

Compensatory mechanisms after genetic manipulations have been documented extensively for the nervous system. In many cases, these mechanisms involve genetic regulation at the transcription or expression level of existing isoforms. We report a novel mechanism by which single neurons compensate for changes in network connectivity by retuning their intrinsic electrical properties.

Analysis of Cx36 knockout does not support tenet that olivary gap junctions are required for complex spike synchronization and normal motor performance.

Electrotonic coupling by gap junctions between neurons in the inferior olive has been claimed to underly complex spike (CS) synchrony of Purkinje cells in the cerebellar cortex and thereby to play a role in the coordination of movements. Here, we investigated the motor performance of mice that lack connexin36 (Cx36), which appears necessary for functional olivary gap junctions. Cx36 null-mutants are not ataxic, they show a normal performance on the accelerating rotorod, and they have a regular walking pattern.

Increased urinary excretion of pyridinium cross-links in cancer patients.

Pyridinoline (PYD) and deoxypyridinoline (DPD), two collagen-based cross-links found in bone, were measured by high-performance liquid chromatography in urine samples from 65 control subjects and 97 patients with either untreated or progressive cancer. Patients with cancer had significantly (P < 0.001) higher urine concentrations of PYD and DPD than did control subjects.