Neuroimaging and Recovery of Language in Aphasia

The use of functional neuroimaging techniques has advanced what is known about the neural mechanisms used to support language processing in aphasia resulting from brain damage. This paper highlights recent findings derived from neuroimaging studies focused on neuroplasticity of language networks, the role of the left and right hemispheres in this process, and studies examining how treatment affects the neurobiology of recovery. We point out variability across studies as well as factors related to this variability, and we emphasize challenges that remain for research

Argument structure effects in action verb naming in static and dynamic conditions

Argument structure, as in the participant roles entailed within the lexical representation of verbs, affects verb processing. Recent neuroimaging studies show that when verbs are heard or read, the posterior temporoparietal region shows increased activation for verbs with greater versus lesser argument structure complexity, usually bilaterally. In addition, patients with agrammatic aphasia show verb production deficits, graded based on argument structure complexity. In the present study, we used fMRI to examine the neural correlates of verb production in overt action naming conditions. In addition, we tested the differential effects of naming when verbs were presented dynamically in video segments versus statically in line drawings. Results showed increased neuronal activity associated with production of transitive as compared to intransitive verbs not only in posterior regions, but also in left inferior frontal cortex. We also found significantly greater activation for transitive versus intransitive action naming for videos compared to pictures in the right inferior and superior parietal cortices, areas associated with object manipulation. These findings indicate that verbs with greater argument structure density engender graded activation of both anterior and posterior portions of the language network and support verb naming deficit patterns reported in lesion studies. In addition, the similar findings derived under video and static picture naming conditions provide validity for using videos in neuroimaging studies, which are more naturalistic and perhaps ecologically valid than using static pictures to investigate action naming

Screen-based identification and validation of four new ion channels as regulators of renal ciliogenesis

©2015. To investigate the contribution of ion channels to ciliogenesis, we carried out a small interfering RNA (siRNA)-based reverse genetics screen of all ion channels in the mouse genome in murine inner medullary collecting duct kidney cells. This screen revealed four candidate ion channel genes: Kcnq1, Kcnj10, Kcnf1 and Clcn4. We show that these four ion channels localize to renal tubules, specifically to the base of primary cilia. We report that human KCNQ1 Long QT syndrome disease alleles regulate renal ciliogenesis; KCNQ1-p. R518X, -p.A178T and -p.K362R could not rescue ciliogenesis after Kcnq1-siRNA-mediated depletion in contrast to wild-type KCNQ1 and benign KCNQ1-p.R518Q, suggesting that the ion channel function of KCNQ1 regulates ciliogenesis. In contrast, we demonstrate that the ion channel function ofKCNJ10 is independent of its effect on ciliogenesis. Our data suggest that these four ion channels regulate renal ciliogenesis through the periciliary diffusion barrier or the ciliary pocket, with potential implication as genetic contributors to ciliopathy pathophysiology. The new functional roles of a subset of ion channels provide new insights into the disease pathogenesis of channelopathies, which might suggest future therapeutic approaches

Do patients with schizophrenia exhibit aberrant salience?

BACKGROUND: It has been suggested that some psychotic symptoms reflect ‘aberrant salience’, related to dysfunctional reward learning. To test this hypothesis we investigated whether patients with schizophrenia showed impaired learning of task-relevant stimulusreinforcement associations in the presence of distracting task-irrelevant cues. METHODS: We tested 20 medicated patients with schizophrenia and 17 controls on a reaction time game, the Salience Attribution Test. In this game, participants made a speeded response to earn money in the presence of conditioned stimuli (CSs). Each CS comprised two visual dimensions, colour and form. Probability of reinforcement varied over one of these dimensions (task-relevant), but not the other (task-irrelevant). Measures of adaptive and aberrant motivational salience were calculated on the basis of latency and subjective reinforcement probability rating differences over the task-relevant and task-irrelevant dimensions respectively. RESULTS: Participants rated reinforcement significantly more likely and responded significantly faster on high-probability reinforced relative to lowprobability reinforced trials, representing adaptive motivational salience. Patients exhibited reduced adaptive salience relative to controls, but the two groups did not differ in terms of aberrant salience. Patients with delusions exhibited significantly greater aberrant salience than those without delusions, and aberrant salience also correlated with negative symptoms. In the controls, aberrant salience correlated significantly with ‘introvertive anhedonia’ schizotypy. CONCLUSIONS: These data support the hypothesis that aberrant salience is related to the presence of delusions in medicated patients with schizophrenia, but are also suggestive of a link with negative symptoms. The relationship between aberrant salience and psychotic symptoms warrants further investigation in unmedicated patients

Neural plasticity and treatment-induced recovery of sentence processing in agrammatism

This study examined patterns of neural activation associated with treatment-induced improvement of complex sentence production (and comprehension) in six individuals with stroke-induced agrammatic aphasia, taking into account possible alterations in blood flow often associated with stroke, including delayed time-to-peak of the hemodynamic response function (HRF) and hypoperfused tissue. Aphasic participants performed an auditory verification fMRI task, processing object cleft, subject cleft, and simple active sentences, prior to and following a course of Treatment of Underlying Forms (TUR; Thompson et al., 2003), a linguistically based approach for treating aphasic sentence deficits, which targeted objective relative clause constructions. The patients also were scanned in a long-trials task to examine HRFs, to account for any local deviations resulting from stroke, and perfusion images were obtained to evaluate regions of hypoperfused tissue. Region-of-interest (ROI) analyses were conducted (bilaterally), modeling participant-specific local HRFs in left hemisphere areas activated by 12 healthy age-matched volunteers performing the same task, including the middle and inferior frontal gyri, precentral gyrus, middle and superior temporal gyri, and insula, and additional regions associated with complex syntactic processing, including the posterior perisylvian and superior parietal cortices. Results showed that, despite individual variation in activation differences from pre- to post-treatment scans in the aphasic participants, main-effects analyses revealed a general shift from left superior temporal activation to more posterior temporoparietal areas, bilaterally. Time-to-peak of these responses correlated negatively with blood flow, as measured with perfusion imaging

Neural plasticity and treatment-induced recovery of sentence processing and production in agrammatism

Six agrammatic speakers were trained on production and processing of object-relative sentence structures, resulting in generalization to less complex sentence structures. The acquired structure-building process reflected by this generalization was shown to be supported by changes in neuronal activation patterns underlying syntactic task execution, as measured with pre and post training functional MRIs. The most prominent neuronal activity upregulation was seen in posterior temporoparietal cortical areas, outside of the core network activated in a group of healthy control subjects during complex syntactic processing

Network modulation during complex syntactic processing

Complex sentence processing is supported by a left-lateralized network including inferior frontal cortex and posterior superior temporal cortex. This study investigates the pattern of connectivity and information flow within this network. We used fMRI BOLD data derived from 12 healthy participants reported in and earlier study (Thompson, C. K., Den Ouden, D. B., Bonakdarpour, B., Garibaldi, K. & Parrish, T. B. (2010b). Neural plasticity and treatment-induced recovery of sentence processing in agrammatism. Neuropsychologia, 48(11), 3211-3227) to identify activation peaks associated with object-cleft over syntactically less complex subject-cleft processing. Directed Partial Correlation Analysis was conducted on time series extracted from participant-specific activation peaks and showed evidence of functional connectivity between four regions, linearly between premotor cortex, inferior frontal gyrus, posterior superior temporal sulcus and anterior middle temporal gyrus. This pattern served as the basis for Dynamic Causal Modeling of networks with a driving input to posterior superior temporal cortex, which likely supports thematic role assignment, and networks with a driving input to inferior frontal cortex, a core region associated with syntactic computation. The optimal model was determined through both frequentist and Bayesian model selection and turned out to reflect a network with a primary drive from inferior frontal cortex and modulation of the connection between inferior frontal and posterior superior temporal cortex by complex sentence processing. The winning model also showed a substantive role for a feedback mechanism from posterior superior temporal cortex back to inferior frontal cortex. We suggest that complex syntactic processing is driven by word-order analysis, supported by inferior frontal cortex, in an interactive relation with posterior superior temporal cortex, which supports verb argument structure processing