Cerebellum and apraxia

Classical tenits posit that the role of the cerebellum is limited to pure sensorimotor control. However, evidence from clinical and imaging studies shows that the cerebellum is crucially involved in nonmotor cognitive and affective functions. Schmahmann and Sherman (1998) [1] introduced the cerebellar cognitive affective syndrome (CCAS), characterised by executive, visuo-spatial, affective and linguistic impairments caused by cerebellar pathology. Apraxia, as a planning, organisation and execution disorder of a skilled motor action (not caused by motor, sensory or intellectual impairment) [2], may be regarded to form part of the executive cluster of CCAS. Indeed, several anatomoclinical studies have confirmed involvement of the cerebellum in at least some types of apraxia, which adds to the nonmotor role of the cerebellum. According to Hugo Liepmann [3], apraxia is thought to evolve from a disruption of the creation, activation or retrieval of movement formulae. These formulae represent the idea of a movement as a visual or acoustic image and are stored in the left parietal lobe. The left prefrontal area subsequently associates these formulae with an inherently stored innervatory pattern to transfer the information to the left primary motor areas. The corpus callosum transfers this information to the right motor cortex if the movement is to be executed by the left limb [3]. Based on some recent clinical evidence we hypothesize that the cerebellum forms an intrinsic part of this connectionist model of Liepmann

Cerebellar Activation During Simple and Complex Bimanual Coordination:an Activation Likelihood Estimation (ALE) Meta-analysis

Bimanual coordination is an important part of everyday life and recruits a large neural network, including the cerebellum. The specific role of the cerebellum in bimanual coordination has not yet been studied in depth, although several studies indicate a differential role of the anterior and posterior cerebellum depending on the complexity of the coordination. An activation likelihood estimation (ALE) meta-analysis was used combining the data of several functional MRI studies involving bimanual coordination tasks with varying complexities to unravel the involvement of the different areas of the cerebellum in simple and complex bimanual coordination. This study confirms the general bimanual network as found by Puttemans et al. (Puttemans et al. in J Neurosci 25:4270-4278, 2005) and highlights the differences between preferred in-phase (simultaneous movements of homologous muscle groups) and anti-phase movement conditions (alternating movements of homologous muscle groups), and more complex, non-preferred bimanual movements (e.g., out-of-phase movements). Our results show a differential role for the anterior and posterior vermis in bimanual coordination, with a role for the anterior vermis in anti-phase and complex bimanual coordination, and an exclusive role for the posterior vermis in complex bimanual movements. In addition, the way complexity was manipulated also seems to play a role in the involvement of the anterior and posterior vermis. We hypothesize that the anterior vermis is involved in sequential/spatial control, while the posterior vermis is involved in temporal control of (bimanual) coordination, though other factors such as (visual) feedback and continuity of the movement also seem to have an impact. More studies are needed to unravel the specific role of the cerebellar vermis in bimanual coordination

Clinicians' views of using cortical auditory evoked potentials (CAEP) in the permanent childhood hearing impairment patient pathway

Objective: To obtain clinicians' views on the use of cortical auditory evoked potentials (CAEP) in the clinical pathway. Design: A questionnaire aimed at clinicians who use the HEARLab system with the Aided Cortical Assessment (ACA) Module. Results compared for Australians (where HEARLab produced) to other countries. Sample: The questionnaire was completed by 49 clinicians; 33 from Australia and 13 clinicians outside of Australia and 3 clinicians, destination unknown. Results: The findings of this research demonstrated that clinicians using CAEPs found them valuable for clinical practice. CAEPs were used to verify or modify hearing aid fittings and were used for counselling parents to reinforce the need for hearing aids. With the use of speech token as the stimulus clinicians had more relevant information to increase confidence in decision-making on paediatric hearing management. Conclusions: The main benefit from the use of CAEPs (using speech token stimuli) was for infant hearing aid fitting programmes, to facilitate earlier decisions relating to hearing aid fitting, for fine-tuning the aids and as an additional measure for cochlear implant referrals

Cerebellar induced differential polyglot aphasia: a neurolinguistic and fMRI study

Research has shown that linguistic functions in the bilingual brain are subserved by similar neural circuits as in monolinguals, but with extra-activity associated with cognitive and attentional control. Although a role for the right cerebellum in multilingual language processing has recently been acknowledged, a potential role of the left cerebellum remains largely unexplored. This paper reports the clinical and fMRI findings in a strongly right-handed (late) multilingual patient who developed differential polyglot aphasia, ataxic dysarthria and a selective decrease in executive function due to an ischemic stroke in the left cerebellum. fMRI revealed that lexical-semantic retrieval in the unaffected L1 was predominantly associated with activations in the left cortical areas (left prefrontal area and left postcentral gyrus), while naming in two affected non-native languages recruited a significantly larger bilateral functional network, including the cerebellum. It is hypothesized that the left cerebellar insult resulted in decreased right prefrontal hemisphere functioning due to a loss of cerebellar impulses through the cerebello-cerebral pathways

Mutant JAK3 phosphoproteomic profiling predicts synergism between JAK3 inhibitors and MEK/BCL2 inhibitors for the treatment of T-cell acute lymphoblastic leukemia

Mutations in the interleukin-7 receptor (IL7R) or the Janus kinase 3 (JAK3) kinase occur frequently in T-cell acute lymphoblastic leukemia (T-ALL) and both are able to drive cellular transformation and the development of T-ALL in mouse models. However, the signal transduction pathways downstream of JAK3 mutations remain poorly characterized. Here we describe the phosphoproteome downstream of the JAK3(L857Q)/(M511I) activating mutations in transformed Ba/F3 lymphocyte cells. Signaling pathways regulated by JAK3 mutants were assessed following acute inhibition of JAK1/JAK3 using the JAK kinase inhibitors ruxolitinib or tofacitinib. Comprehensive network interrogation using the phosphoproteomic signatures identified significant changes in pathways regulating cell cycle, translation initiation, mitogen-activated protein kinase and phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/AKT signaling, RNA metabolism, as well as epigenetic and apoptotic processes. Key regulatory proteins within pathways that showed altered phosphorylation following JAK inhibition were targeted using selumetinib and trametinib (MEK), buparlisib (PI3K) and ABT-199 (BCL2), and found to be synergistic in combination with JAK kinase inhibitors in primary T-ALL samples harboring JAK3 mutations. These data provide the first detailed molecular characterization of the downstream signaling pathways regulated by JAK3 mutations and provide further understanding into the oncogenic processes regulated by constitutive kinase activation aiding in the development of improved combinatorial treatment regimens

Mutant JAK3 phosphoproteomic profiling predicts synergism between JAK3 inhibitors and MEK/BCL2 inhibitors for the treatment of T-cell acute lymphoblastic leukemia (vol 32, pg 788, 2018)

Following the publication of this article the authors noted that data describing precisely where phosphorylation sites in proteins modulated following JAK1 or JAK3 inhibition in mutant T-ALL samples was not clearly annotated. Therefore an additional sheet has been added to Supplementary Table 2

Metal Cation Pre Intercalated Ti3C2Tx MXene as Ultra High Areal Capacitance Electrodes for Aqueous Supercapacitors

Two dimensional transition metal carbides and nitrides MXenes have demonstrated great potential as electrode materials for electrochemical energy storage systems. This is especially true for delaminated Ti3C2Tx, which already shows outstanding gravimetric and volumetric capacitance, with areal capacitance limited by thickness only a few microns . However, the performance of multilayer Ti3C2Tx has been more modest. Here, we report on using metal cation viz., Na , K , and Mg2 pre intercalated multilayer Ti3C2Tx as electrodes for aqueous supercapacitors. These electrodes are scalable and amenable to roll to roll manufacturing, with adjustable areal loadings of 5.2 to 20.1 mg cm2. K Ti3C2Tx exhibited the highest capacitances at different scan rates. A gravimetric capacitance comparable to that of delaminated MXene of up to 300 F g was achieved for multilayer K Ti3C2Tx but with an outstanding ultra high areal capacitance of up to 5.7 F cm2, which is 10 fold higher than the 0.5 F cm2 of delaminated MXene and exceeds the 4.0 F cm2 of microengineered MXene electrode

Time-dependent Stochastic Modeling of Solar Active Region Energy

A time-dependent model for the energy of a flaring solar active region is presented based on a stochastic jump-transition model (Wheatland and Glukhov 1998; Wheatland 2008; Wheatland 2009). The magnetic free energy of the model active region varies in time due to a prescribed (deterministic) rate of energy input and prescribed (random) flare jumps downwards in energy. The model has been shown to reproduce observed flare statistics, for specific time-independent choices for the energy input and flare transition rates. However, many solar active regions exhibit time variation in flare productivity, as exemplified by NOAA active region AR 11029 (Wheatland 2010). In this case a time-dependent model is needed. Time variation is incorporated for two cases: 1. a step change in the rates of flare jumps; and 2. a step change in the rate of energy supply to the system. Analytic arguments are presented describing the qualitative behavior of the system in the two cases. In each case the system adjusts by shifting to a new stationary state over a relaxation time which is estimated analytically. The new model retains flare-like event statistics. In each case the frequency-energy distribution is a power law for flare energies less than a time-dependent rollover set by the largest energy the system is likely to attain at a given time. For Case 1, the model exhibits a double exponential waiting-time distribution, corresponding to flaring at a constant mean rate during two intervals (before and after the step change), if the average energy of the system is large. For Case 2 the waiting-time distribution is a simple exponential, again provided the average energy of the system is large. Monte Carlo simulations of Case~1 are presented which confirm the analytic estimates. The simulation results provide a qualitative model for observed flare statistics in active region AR 11029.Comment: 25 pages, 9 figure

Constraint-induced Aphasia Therapy versus Intensive Semantic Treatment in Fluent Aphasia

Objective: To compare the effectiveness of two intensive therapy methods: Constraint- 4 Induced Aphasia Therapy (CIAT) and semantic therapy (BOX). Method: Nine patients with chronic fluent aphasia participated in a therapy programme 6 to establish behavioral treatment outcomes. Participants were randomly assigned to one of two groups (CIAT or BOX). Results: Intensive therapy significantly improved verbal communication. However, BOX 9 treatment showed a more pronounced improvement on two communication measures, namely on a standardized assessment for verbal communication, the Amsterdam Nijmegen Everyday Language Test (Blomert, Koster, & Kean, 1995) and on a subjective rating scale, the Communicative Effectiveness Index (Lomas et al., 1989). All 13 participants significantly improved on one (or more) subtests of the Aachen Aphasia Test (Graetz et al., 1992), an impairment-focused assessment. There was a treatment-specific effect. Therapy with BOX had a significant effect on language comprehension and on semantics, while of CIAT affected language production and phonology. Conclusion: The findings indicate that in patients with fluent aphasia (1) intensive treatment has a significant effect on language and verbal communication, (2) intensive therapy results in selective treatment effects and (3) an intensive semantic treatment shows a more striking mean improvement on verbal communication in comparison to communication-based CIAT-treatment