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1.  Individualized treatment with transcranial direct current stimulation in patients with chronic non-fluent aphasia due to stroke 
While evidence suggests that transcranial direct current stimulation (tDCS) may facilitate language recovery in chronic post-stroke aphasia, individual variability in patient response to different patterns of stimulation remains largely unexplored. We sought to characterize this variability among chronic aphasic individuals, and to explore whether repeated stimulation with an individualized optimal montage could lead to persistent reduction of aphasia severity. In a two-phase study, we first stimulated patients with four active montages (left hemispheric anode or cathode; right hemispheric anode or cathode) and one sham montage (Phase 1). We examined changes in picture naming ability to address (1) variability in response to different montages among our patients, and (2) whether individual patients responded optimally to at least one montage. During Phase 2, subjects who responded in Phase 1 were randomized to receive either real-tDCS or to receive sham stimulation (10 days); patients who were randomized to receive sham stimulation first were then crossed over to receive real-tDCS (10 days). In both phases, 2 mA tDCS was administered for 20 min per real-tDCS sessions and patients performed a picture naming task during stimulation. Patients' language ability was re-tested after 2-weeks and 2-months following real and sham tDCS in Phase 2. In Phase 1, despite considerable individual variability, the greatest average improvement was observed after left-cathodal stimulation. Seven out of 12 subjects responded optimally to at least one montage as demonstrated by transient improvement in picture-naming. In Phase 2, aphasia severity improved at 2-weeks and 2-months following real-tDCS but not sham. Despite individual variability with respect to optimal tDCS approach, certain montages result in consistent transient improvement in persons with chronic post-stroke aphasia. This preliminary study supports the notion that individualized tDCS treatment may enhance aphasia recovery in a persistent manner.
PMCID: PMC4404833  PMID: 25954178
tDCS; aphasia; stroke; language disorders; neurorehabilitation
2.  Voxel-based lesion-parameter mapping: Identifying the neural correlates of a computational model of word production 
Cognition  2013;128(3):380-396.
The dual-route interactive two-step model explains the variation in the error patterns of aphasic speakers in picture naming, and word and nonword repetition tasks. The model has three parameters that can vary across individuals: the efficiency of the connections between semantic and lexical representations (s-weight), between lexical and phonological representations (p-weight), and between representations of auditory input and phonological representations (nl-weight). We determined these parameter values in 103 participants with chronic aphasia from left hemisphere stroke whose lesion locations had been determined. Then, using voxel-based lesion-parameter mapping, we mapped the parameters onto the brain, thus determining the neural correlates of the model’s mechanisms. The maps and the behavioral findings supported the model’s central claim that word repetition is affected by both the p and nl parameters. We propose that these two parameters constitute the model’s analogue of the “dorsal stream” component of neurocognitive models of language processing.
PMCID: PMC3709005  PMID: 23765000
Aphasia; Language production; Computational models; Voxel-based Lesion Parameter Mapping
3.  The dorsal stream contribution to phonological retrieval in object naming 
Brain  2012;135(12):3799-3814.
Meaningful speech, as exemplified in object naming, calls on knowledge of the mappings between word meanings and phonological forms. Phonological errors in naming (e.g. GHOST named as ‘goath’) are commonly seen in persisting post-stroke aphasia and are thought to signal impairment in retrieval of phonological form information. We performed a voxel-based lesion-symptom mapping analysis of 1718 phonological naming errors collected from 106 individuals with diverse profiles of aphasia. Voxels in which lesion status correlated with phonological error rates localized to dorsal stream areas, in keeping with classical and contemporary brain-language models. Within the dorsal stream, the critical voxels were concentrated in premotor cortex, pre- and postcentral gyri and supramarginal gyrus with minimal extension into auditory-related posterior temporal and temporo-parietal cortices. This challenges the popular notion that error-free phonological retrieval requires guidance from sensory traces stored in posterior auditory regions and points instead to sensory-motor processes located further anterior in the dorsal stream. In a separate analysis, we compared the lesion maps for phonological and semantic errors and determined that there was no spatial overlap, demonstrating that the brain segregates phonological and semantic retrieval operations in word production.
PMCID: PMC3525060  PMID: 23171662
aphasia; dual-stream; voxel-based lesion-symptom mapping; naming; phonological errors; semantic errors
4.  The right hemisphere is not unitary in its role in aphasia recovery 
Neurologists and aphasiologists have debated for over a century whether right hemisphere recruitment facilitates or impedes recovery from aphasia. Here we present a well-characterized patient with sequential left and right hemisphere strokes whose case substantially informs this debate. A 72-year-old woman with chronic nonfluent aphasia was enrolled in a trial of transcranial magnetic stimulation (TMS). She underwent 10 daily sessions of inhibitory TMS to the right pars triangularis. Brain activity was measured during picture naming using fMRI prior to TMS exposure and before and after TMS on the first day of treatment. Language and cognition were tested behaviorally three times prior to treatment, and at 2 and 6 months afterwards. Inhibitory TMS to the right pars triangularis induced immediate improvement in naming, which was sustained 2 months later. FMRI confirmed a local reduction in activity at the TMS target, without expected increased activity in corresponding left hemisphere areas. Three months after TMS, the patient suffered a right hemisphere ischemic stroke, resulting in worsening of aphasia without other clinical deficits. Behavioral testing 3 months later confirmed that language function was impacted more than other cognitive domains. The paradoxical effects of inhibitory TMS and the stroke to the right hemisphere demonstrate that even within a single patient, involvement of some right hemisphere areas may support recovery, while others interfere. The behavioral evidence confirms that compensatory reorganization occurred within the right hemisphere after the original stroke. No support is found for interhemispheric inhibition, the theoretical framework on which most therapeutic brain stimulation protocols for aphasia are based.
PMCID: PMC3221765  PMID: 21794852
aphasia; transcranial magnetic stimulation; plasticity; neuromodulation; interhemispheric inhibition
5.  Finding the Right Words: Transcranial Magnetic Stimulation Improves Discourse Productivity in Non-fluent Aphasia After Stroke 
Aphasiology  2012;26(9):1153-1168.
Loss of fluency is a significant source of functional impairment in many individuals with aphasia. Repetitive transcranial magnetic stimulation (rTMS) administered to the right inferior frontal gyrus (IFG) has been shown to facilitate naming in persons with chronic left hemisphere stroke and non-fluent aphasia. However, changes in fluency in aphasic subjects receiving rTMS have not been adequately explored.
To determine whether rTMS improves fluency in individuals with chronic nonfluent aphasia, and to identify aspects of fluency that are modulated in persons who respond to rTMS.
Methods & Procedures
Ten individuals with left hemisphere MCA strokes and mild to moderate non-fluent aphasia participated in the study. Before treatment, subjects were asked to describe the Cookie Theft picture in three separate sessions. During treatment, all subjects received 1200 pulses of 1 Hz rTMS daily in 10 sessions over two weeks at a site that had previously been shown to improve naming. Subjects repeated the Cookie Theft description two months after treatment. Five subjects initially received sham stimulation instead of real TMS. Two months after sham treatment, these individuals received real rTMS. Performance both at baseline and after stimulation was coded using Quantitative Production Analysis (Saffran, Berndt & Schwartz, 1989) and Correct Information Unit (Nicholas & Brookshire, 1993) analysis.
Outcomes & Results
Across all subjects (n=10), real rTMS treatment resulted in a significant increase in multiple measures of discourse productivity compared to baseline performance. There was no significant increase in measures of sentence productivity or grammatical accuracy. There was no significant increase from baseline in the sham condition (n=5) on any study measures.
Stimulation of the right IFG in patients with chronic non-fluent aphasia facilitates discourse production. We posit that this effect may be attributable to improved lexical-semantic access.
PMCID: PMC3532848  PMID: 23280015
Language; aphasia; TMS; pars triangularis; fluency; neurorehabilitation
6.  Support for Anterior Temporal Involvement in Semantic Error Production in Aphasia: New Evidence from VLSM 
Brain and language  2010;117(3):110-122.
Semantic errors in aphasia (e.g., naming a horse as “dog”) frequently arise from faulty mapping of concepts onto lexical items. A recent study by our group used voxel-based lesion-symptom mapping (VLSM) methods with 64 patients with chronic aphasia to identify voxels that carry an association with semantic errors. The strongest associations were found in the left anterior temporal lobe (L-ATL), in the mid- to anterior MTG region. The absence of findings in Wernicke’s area was surprising, as were indications that ATL voxels made an essential contribution to the post-semantic stage of lexical access. In this follow-up study, we sought to validate these results by re-defining semantic errors in a manner that was less theory dependent and more consistent with prior lesion studies. As this change also increased the robustness of the dependent variable, it made it possible to perform additional statistical analyses that further refined the interpretation. The results strengthen the evidence for a causal relationship between ATL damage and lexically-based semantic errors in naming and lend confidence to the conclusion that chronic lesions in Wernicke’s area are not causally implicated in semantic error production.
PMCID: PMC3037437  PMID: 20961612
aphasia; voxel-based lesion-symptom mapping; naming; semantic; errors
7.  Stimulating Conversation: Enhancement of Elicited Propositional Speech in a Patient with Chronic Nonfluent Aphasia Following Transcranial Magnetic Stimulation 
Brain and language  2010;113(1):45-50.
Although evidence suggests that patients with left hemisphere strokes and nonfluent aphasia who receive 1 Hz repetitive transcranial magnetic stimulation (rTMS) over the intact right inferior frontal gyrus experience persistent benefits in naming, it remains unclear whether the effects of rTMS in these patients generalize to other language abilities. We report a subject with chronic nonfluent aphasia who showed stable deficits of elicited propositional speech over the course of five years, and received 1200 pulses of 1 Hz rTMS daily for 10 days at a site identified as being optimally responsive to rTMS in this patient. Consistent with prior studies there was improvement in object naming, with a statistically significant improvement in action naming. Improvement was also demonstrated in picture description at 2, 6, and 10 months after rTMS with respect to the number of narrative words and nouns, sentence length, and use of closed class words. Compared to his baseline performance, the patient showed significant improvement on the Western Aphasia Battery subscale for spontaneous speech. These findings suggest that manipulation of the intact contralesional cortex in patients with nonfluent aphasia may result in language benefits that generalize beyond naming to include other aspects of language production.
PMCID: PMC2909623  PMID: 20159655
Interhemispheric interactions; language; TMS; inferior frontal gyrus; discourse; propositional speech
8.  Anterior temporal involvement in semantic word retrieval: voxel-based lesion-symptom mapping evidence from aphasia 
Brain  2009;132(12):3411-3427.
Analysis of error types provides useful information about the stages and processes involved in normal and aphasic word production. In picture naming, semantic errors (horse for goat) generally result from something having gone awry in lexical access such that the right concept was mapped to the wrong word. This study used the new lesion analysis technique known as voxel-based lesion-symptom mapping to investigate the locus of lesions that give rise to semantic naming errors. Semantic errors were obtained from 64 individuals with post-stroke aphasia, who also underwent high-resolution structural brain scans. Whole brain voxel-based lesion-symptom mapping was carried out to determine where lesion status predicted semantic error rate. The strongest associations were found in the left anterior to mid middle temporal gyrus. This area also showed strong and significant effects in further analyses that statistically controlled for deficits in pre-lexical, conceptualization processes that might have contributed to semantic error production. This study is the first to demonstrate a specific and necessary role for the left anterior temporal lobe in mapping concepts to words in production. We hypothesize that this role consists in the conveyance of fine-grained semantic distinctions to the lexical system. Our results line up with evidence from semantic dementia, the convergence zone framework and meta-analyses of neuroimaging studies on word production. At the same time, they cast doubt on the classical linkage of semantic error production to lesions in and around Wernicke's area.
PMCID: PMC2792374  PMID: 19942676
aphasia; voxel-based lesion-symptom mapping; naming; semantic; errors

Results 1-8 (8)