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Dirk Plas Group

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Andrew Grindberg
Andrew Grindberg

Adynamia



Dynamic aphasia has been documented in association with various focal brain lesions involving the dominant frontal lobe and its connections (Blank et al., 2002; Braun, Guillemin, Hosey, & Varga, 2001; Robinson, 2013; Wagner et al., 2001) as well as neurodegenerative syndromes implicating this circuitry, notably PSP (Bak, Hodges, & Thomas, 2008; ; Esmonde et al., 1996; Litvan et al., 1996; Robinson, 2013; Robinson et al., 2015; Warren et al., 2003). Propositional speech production is mediated by a distributed neural network including left superior and inferior frontal gyri, frontal operculum, and posterior superior temporal cortex (Blank et al., 2002; Braun et al., 2001; Wagner et al., 2001). Disruption of these fronto-subcortical networks and, more particularly, dopaminergic projection pathways is clearly a candidate substrate for development of verbal adynamia across parkinsonian disorders (Robinson, 2013). However, disentangling the role of motor, executive, and primary linguistic impairments in the context of parkinsonism is challenging. Moreover, the neuroanatomical basis of neurolinguistic and related cognitive impairments in the parkinsonian spectrum and the potentially modulatory effects of dopaminergic therapy remain incompletely defined.




adynamia



Performance on verbal generation tasks was compared between participant groups using a linear regression model, covarying for potentially confounding (nuisance) factors of gender and linguistic control task performance (lexical retrieval, Graded Naming Test score; sentence assembly, expressive grammar score). Verbal generation is likely a priori to be closely aligned to other cognitive control and generative processes: for the purposes of the present analysis, we incorporated WASI Matrices score (a standard measure of general nonverbal cognitive flexibility) as an additional nuisance covariate in the regression model. We did not attempt to adjust for design fluency (a measure of nonverbal pattern generation) in the same regression model but rather assessed correlation between verbal and nonverbal generation measures separately, as these measures might a priori be more closely and specifically associated (so covariation might therefore parcel out the effect of interest). All verbal adynamia battery data were non-normally distributed; accordingly, nonparametric, bias-corrected, and accelerated, bootstrap confidence intervals were calculated from 2,000 replications. In order to assess performance on the fluency tasks, scores were first converted into standardized z-scores based on mean (standard deviation) data from the healthy control group as a reference; paired t-tests were used to compare performance on different fluency tests in each participant group and two sample t-tests were used for comparison between groups. In order to assess the effect of dopaminergic medication on verbal adynamia battery performance in the PDD group, ON and OFF state data (for stimulus sets A and B) were compared using Wilcoxon signed-rank tests.


The VBM evidence in the combined patient cohort here suggests a plausible, common neuroanatomical substrate for verbal adynamia in these parkinsonian syndromes, after taking into account the effects of general executive or linguistic compromise (as indexed by WASI Matrices and Graded Naming Test performance). The present evidence implicates core inferior frontal and posterior superior temporal components of the dominant hemisphere language network: similar cortical regions have been linked to propositional speech output in the healthy brain (Wagner et al., 2001) and have been previously shown to be damaged in PDD, CBS, and PSP (Boxer et al., 2006). More specifically, this dominant hemisphere fronto-striatal network (and within this network, left inferior frontal cortex) has been linked to the pathogenesis of dynamic aphasia in detailed case studies of patients with neurodegenerative and focal brain pathologies (Costello & Warrington., 1989; Esmonde et al., 1996; Robinson, 2013; Robinson et al., 2006, 2015; Rohrer et al., 2010). Our study was not equipped to resolve the several candidate mechanisms that have been proposed to underpin dynamic aphasia; however, inferior frontal cortex is likely to be involved in discourse and fluent thought sequencing, as well as verbal response selection, all of which are potentially vulnerable in parkinsonian disorders (Boxer et al., 2006). Our patient cohort showed deficits both on design fluency and verbal generation tasks, as would be anticipated with a domain-general generative impairment (Robinson et al., 2015); however, these verbal and nonverbal deficits were uncorrelated over the cohort while only verbal performance showed dopaminergic modulation, which at least raises the possibility of dissociable processes.


Dominantly inherited sodium channel disorder with onset in early childhood, (abating in adult life), manifesting recurrent brief attacks of proximal muscle weakness, flaccidity, myotonia and occasionally cardia rhythm disturbances. [aka * familial periodic paralysis type 2; hyperkalemic familial periodic paralysis; adynamia episodica hereditaria; paramyotonia congenita, hyperkalemic periodic paralysis]


American trypanosomiasis (Chagas' disease) is an endemic parasitic disease afflicting more than 20 million persons in Latin America. Two drugs are currently being used for treatment of the acute phase of Chagas' disease: 4-[(5-nitrofurfurylidene)amino-3-methylthiomorpholine-1,1-di oxide] (Nifurtimox; Nfx) and (N-benzl-2-nitro-1-imidazole acetamide) (Benznidazole; Bz). Nfx and Bz have serious undesirable effects, which have been reported during their clinical use, including anorexia and weight loss, nausea and vomiting, nervous excitation, insomnia, psyche depressions, convulsions, vertigo, headache, sleepiness, myalgias, arthralgias, loss of balance, disorientation, forgetfulness, paresthesias, adynamia, acoustic phenomena, peripheral neuropathies, gastralgia, mucosal edema, hepatic intolerance, skin manifestations, and intolerance to drinking alcohol. Effects in the central and peripheral nervous system of Nfx were also reproduced in animals. Signs of testicular and ovarian injury were reported for both Nfx and Bz, the effects of Bz being in general less intense than those of Nfx. Both drugs evidenced mutagenicity. In light of the present knowledge about the toxicity of Nfx and Bz, further studies on the mutagenic, teratogenic, carcinogenic, and reproductive effects of both drugs are recommended. Lack of information is particularly serious for Bz. Studies on Nfx and Bz biotransformation, activation to reactive metabolites, and potential mechanisms for their toxic effects were analyzed. Risk-benefit considerations of the use of Nfx and Bz were made and an analysis of the need for research on Chagas' disease chemotherapy was also performed. 041b061a72


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Members

  • Dirk Erik Plas
  • Fedor Hunchback
    Fedor Hunchback
  • Jacob Turner
    Jacob Turner
  • Andrew Grindberg
    Andrew Grindberg
  • Waylon Green
    Waylon Green
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