Borna Bonakdarpour

Hemodynamic response function in patients with stroke-induced aphasia: implications for fMRI data analysis.

Functional MRI is based on changes in cerebral microvasculature triggered by increased neuronal oxidative metabolism. This change in blood flow follows a pattern known as the hemodynamic response function (HRF), which typically peaks 4-6 s following stimulus delivery. However, in the presence of cerebrovascular disease the HRF may not follow this normal pattern, due to either the temporal signal to noise (tSNR) ratio or delays in the HRF, which may result in misinterpretation or underestimation of fMRI signal. The present study examined the HRF and SNR in five individuals with aphasia resulting from stroke and four unimpaired participants using a lexical decision task and a long trial event-related design. T1-weighted images were acquired using an MP-RAGE sequence and BOLD T2*-weighted images were acquired using Echo Planar Imaging to measure time to peak (TTP) in the HRF. Data were analyzed using Brain Voyager in four anatomic regions known to be involved in language processing: Brocas area and the posterior perisylvian network (PPN) (including Wernickes area, the angular and supramarginal gyri) and right hemisphere homologues of these regions. The occipital area also was examined as a control region. Analyses showed that the TTP in three out of five patients in the left perisylvian area was increased significantly as compared to normal individuals and the left primary visual cortex in the same patients. In two other patients no significant delays were detected. We also found that the SNR for BOLD signal detection may by insufficient in damaged areas. These findings indicate that obtaining physiologic (TTP) and quality assurance (tSNR) information is essential for studying activation patterns in brain-damaged patients in order to avoid errors in interpretation of the data. An example of one such misinterpretation and the need for alternative data analysis strategies is discussed.

Neural correlates of verb argument structure processing

Neuroimaging and lesion studies suggest that processing of word classes, such as verbs and nouns, is associated with distinct neural mechanisms. Such studies also suggest that subcategories within these broad word class categories are differentially processed in the brain. Within the class of verbs, argument structure provides one linguistic dimension that distinguishes among verb exemplars, with some requiring more complex argument structure entries than others. This study examined the neural instantiation of verbs by argument structure complexity: one-, two-, and three-argument verbs. Stimuli of each type, along with nouns and pseudowords, were presented for lexical decision using an event-related functional magnetic resonance imaging design. Results for 14 young normal participants indicated largely overlapping activation maps for verbs and nouns, with no areas of significant activation for verbs compared to nouns, or vice versa. Pseudowords also engaged neural tissue overlapping with that for both word classes, with more widespread activation noted in visual, motor, and peri-sylvian regions. Examination of verbs by argument structure revealed activation of the supramarginal and angular gyri, limited to the left hemisphere only when verbs with two obligatory arguments were compared to verbs with a single argument. However, bilateral activation was noted when both two- and three-argument verbs were compared to one-argument verbs. These findings suggest that posterior peri-sylvian regions are engaged for processing argument structure information associated with verbs, with increasing neural tissue in the inferior parietal region associated with increasing argument structure complexity. These findings are consistent with processing accounts, which suggest that these regions are crucial for semantic integration.

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 (TUF; Thompson et al., 2003), a linguistically based approach for treating aphasic sentence deficits, which targeted object 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.

Positive Effects of Language Treatment for the Logopenic Variant of Primary Progressive Aphasia

Despite considerable recent progress in understanding the underlying neurobiology of primary progressive aphasia (PPA) syndromes, relatively little attention has been directed toward the examination of behavioral interventions that may lessen the pervasive communication problems associated with PPA. In this study, we report on an individual with a behavioral profile and cortical atrophy pattern consistent with the logopenic variant of PPA. At roughly two-and-a-half years post onset, his marked lexical retrieval impairment prompted administration of a semantically based intervention to improve word retrieval. The treatment was designed to improve self-directed efforts to engage the participant’s relatively preserved semantic system in order to facilitate word retrieval. His positive response to an intensive (2-week) dose of behavioral treatment was associated with improved lexical retrieval of items within trained categories, and generalized improvement for naming of untrained items that lasted over a 6-month follow-up interval. These findings support the potential value of intensive training to achieve self-directed strategic compensation for lexical retrieval difficulties in logopenic PPA. Additional insight was gained regarding the neural regions that supported improved performance by the administration of a functional magnetic resonance imaging protocol before and after treatment. In the context of a picture-naming task, post-treatment fMRI showed increased activation of left dorsolateral prefrontal regions that have been implicated in functional imaging studies of generative naming in healthy individuals. The increased activation in these frontal regions that were not significantly atrophic in our patient (as determined by voxel-based morphometry) is consistent with the notion that neural plasticity can support compensation for specific language loss, even in the context of progressive neuronal degeneration.

Asymmetric connectivity between the anterior temporal lobe and the language network

The anterior temporal lobe (ATL) sits at the confluence of auditory, visual, olfactory, transmodal, and limbic processing hierarchies. In keeping with this anatomical heterogeneity, the ATL has been implicated in numerous functional domains, including language, semantic memory, social cognition, and facial identification. One question that has attracted considerable discussion is whether the ATL contains a mosaic of differentially specialized areas or whether it provides a domain-independent amodal hub. In the current study, based on task-free fMRI in right-handed neurologically intact participants, we found that the left lateral ATL is interconnected with hubs of the temporosylvian language network, including the inferior frontal gyrus and middle temporal gyrus of the ipsilateral hemisphere and, to a lesser extent, with homotopic areas of the contralateral hemisphere. In contrast, the right lateral ATL had much weaker functional connectivity with these regions in either hemisphere. Together with evidence that has been gathered in lesion-mapping and event-related neuroimaging studies, this asymmetry of functional connectivity supports the inclusion of the left ATL within the language network, a relationship that had been overlooked by classic aphasiology. The asymmetric domain selectivity for language of the left ATL, together with the absence of such an affiliation in the right ATL, is inconsistent with a strict definition of domain-independent amodal functionality in this region of the brain.

Melodic intonation therapy in Persian aphasic patients

Background : Melodic intonation therapy (MIT) is a well-known method of aphasia rehabilitation using prosodically based melodic phrases. The literature includes MIT adapted to many languages and efficiently applied to certain groups of non-fluent aphasic patients. However, there has been no report on the efficacy of the method for Persian-speaking patients. Aims : The objective of this study was primarily to investigate the effects of 15 sessions of MIT treatment (adapted to the Persian language) in selected patients with non-fluent aphasia; primarily on expository speech (phrase length and number of correct content units) and oral expression skills (repetition, responsive naming, and confrontational naming), and secondarily, on auditory comprehension abilities (word discrimination, commands). Methods and Procedures : Participants in the study included seven right-handed Persian-speaking patients afflicted with chronic (>14 months post-onset) non-fluent aphasia. Based on the rules of Persian prosody, MIT was adapted to the Persian language. Using a pre, post treatment design, each outcome measure was tested twice before and twice after MIT treatment. Changes in the variables not treated were also measured as baselines controlling treatment effects. Outcomes and Results : Using the Wilcoxon signed-rank test, improvements in the selected variables were shown to be statistically significant after the treatment phase and not during the treatment-free phases. Non-target variables remained unchanged after the treatment and throughout the non-treatment phases. Conclusions : Our study showed that MIT can be adapted for Persian aphasic patients and administered with measurable positive results after 15 sessions of treatment. MIT improved primarily spontaneous speech production, and as minor effects, selected oral expression and auditory comprehension subtests. Therefore MIT might be considered as a method for the rehabilitation of selected non-fluent Persian aphasic patients. More long-term follow-up studies with randomised controlled clinical trials are needed for stronger conclusions.

Neural correlates of covert and overt production of tense and agreement morphology: Evidence from fMRI.

Most neuroimaging studies examining verb morphology have focused on verb tense, with fewer examining agreement morphology, and no previous fMRI studies have investigated distinctions between past and present tense inflection. However, models of language representation and processing suggest differences in where these inflections are instantiated in the phrase structure as well as differences in the linguistic functions they serve, suggesting unique neural networks for these forms. In addition, results of available neuroimaging studies of grammatical morphology vary considerably due to methodological differences. Some studies have used overt production tasks, whereas others have used covert tasks. In the present study we examined brain activation associated with past tense and present tense/agreement morphology under overt and covert production conditions in 13 healthy adults using an event-related functional magnetic resonance imaging (fMRI) design. Production of verbs inflected for past tense (V + -ed) and present tense/agreement (V -s) was elicited using temporal adverbs (i.e. Yesterday, Nowadays). Results showed that in healthy adults inflecting both past tense and agreement morphology (compared to a verb stem production condition) recruited not only left inferior frontal structures, but also motor and premotor cortices, and posterior parietal regions. Activation also was observed in the basal ganglia, thalamus, and the cingulate gyrus. Past tense and present tense/agreement recruited partially overlapping tissue in these regions, with distinctions observed for the two forms in frontal and parietal brain areas. We also found that activation varied with task demands, with more extensive frontal activation noted in the overt compared to the covert verb inflection task. These results are consistent with the hypothesis that the neural signatures for verb inflection differ from that for verb stems alone and involve a distributed frontal and parietal network of brain regions. Further, the neural tissue recruited for instantiation of past tense versus present tense/agreement morphology is distinct, supporting linguistic theories that differentiate the two forms.

Semantic Interference during Object Naming in Agrammatic and Logopenic Primary Progressive Aphasia (PPA)

This study examined the time course of object naming in 21 individuals with primary progressive aphasia (PPA) (8 agrammatic (PPA-G); 13 logopenic (PPA-L)) and healthy age-matched speakers (n=17) using a semantic interference paradigm with related and unrelated interfering stimuli presented at stimulus onset asynchronies (SOAs) of -1000, -500, -100 and 0 ms. Results showed semantic interference (SI) (i.e. significantly slower RTs in related compared to unrelated conditions) for all groups at -500, -100 and 0 ms, indicating timely spreading activation to semantic competitors. However, both PPA groups showed a greater magnitude of SI than normal across SOAs. The PPA-L group and six PPA-G participants also evinced SI at -1000 ms, suggesting an abnormal time course of semantic interference resolution, and concomitant left hemisphere cortical atrophy in brain regions associated with semantic processing. These subtle semantic mapping impairments in non-semantic variants of PPA may contribute to the anomia of these patients.

Functional category production in agrammatism: Treatment and generalization effects

Department of Neurology, Northwestern University, USAAccepted 6 July 2006IntroductionThe complexity account of treatment efficacy (CATE; Thompson,Shapiro, Kiran, & Sobecks, 2003) predicts that training complex languagestructures in agrammatism will result in generalize to less complex struc-tures, but only when they share similar derivations. For instance, trainingcomplex sentences derived by ‘wh’ movement, such as object clefts (e.g., Itwas the coach who the skater chased) results in generalization to less com-plex ‘wh’ movement structures such as object-extracted wh questions (Whodid the skater chase?), but not to ‘NP’ movement structures (e.g. passivevoice: The coach was chased by the skater). To date, CATE has been testedwith noncanonical sentence structures, which are particularly difficult foragrammatic speakers. In this paper, we examined the generalization pat-terns that result from training functional morphology in basic canonicalsentences. Specifically, we examined patterns of acquisition and general-ization of:(1) Complementizers: They wonder if the cat is following the mouse.(2) Past tense inflections: Yesterday the cat followed the mouse.(3) Presentagreement inflections: Nowadaysthe cat follows the mouse.While all three morphemes are considered functional category mem-bers, complementizers and tense/agreement are not equivalent with respectto their structural position in the syntactic tree. Complementizers are ele-ments generated in the complementizer phrase (CP); while tense and agree-ment inflections are both elements licensed by the inflection phrase (IP).Therefore, based on CATE, we predicted generalization between tense(2) and agreement (3), but NOT between complementizers (1) and tense(2) or between complementizers (1) and agreement (3), since they arelicensed by distinct functional projections.In contrast to CATE,the Tree pruninghypothesis (TPH; FriedmannG Thompson, 2005), and spontaneouslanguage patterns. Participants were between 36–68 years old, and hadbetween 12–20 years of education.Design and analysisA single subject multiple baseline design across behaviors and partici-pants was used. Pre- and post-testing measures included the Westernaphasia battery (WAB; Kertesz, 1982), the Verb Inflection Test (VIT;Bastiaanse & Thompson, 2005), and two neuroimaging (fMRI) tasksdesigned to examine neural patterns associated with production and com-prehension of the target morphemes. Baseline probes were also adminis-tered to assess production of all target morpheme using picture stimuli(line drawings).During each treatment session participants were asked to produce 15sentences containing the target morpheme. Three types of sentences weretrained: those with complementizers (1), past tense (2), and present tense(3). Training included: (a) thematic role training, (b) placement of writtensentence constituent cards in their surface structure position, (c) readingtarget sentences, (d) reassembly of scrambled written sentence constituentcards, and (d) re-reading sentences. Prior to each session probes, identicalto baseline, were administered to evaluate learning and generalizationpatterns.doi:10.1016/j.bandl.2006.06.049

Variability in blood oxygen level dependent (BOLD) signal in patients with stroke-induced and primary progressive aphasia

Although fMRI is increasingly used to assess language-related brain activation in patients with aphasia, few studies have examined the hemodynamic response function (HRF) in perilesional, and contralesional areas of the brain. In addition, the relationship between HRF abnormalities and other variables such as lesion size and severity of aphasia has not been explored. The objective of this study was to investigate changes in HRF signal during language-related neural activation in patients with stroke-induced aphasia (SA). We also examined the status of the HRF in patients with aphasia due to nonvascular etiology, namely, primary progressive aphasia (PPA). Five right handed SA patients, three PPA patients, and five healthy individuals participated in the study. Structural damage was quantified with T1-weighted MR images. Functional MR imaging was performed with long trial event-related design and an overt naming task to measure BOLD signal time to peak (TTP) and percent signal change (ΔS). In SA patients, the average HRF TTP was significantly delayed in the left hemisphere regions involved in naming compared to healthy participants and PPA patients. However, ΔS was not different in SA patients compared to the other two groups. Delay in HRF TTP in the left hemisphere naming network of SA patients was correlated with lesion size and showed a negative correlation with global language function. There were no significant differences in the HRF TTP and ΔS in the right hemisphere homologues of the naming network or in the left and the right occipital control regions across the three groups. In PPA patients, HRF had a normal pattern. Our results indicate that abnormal task-related HRF is primarily found in the left hemisphere language network of SA patients and raise the possibility that abnormal physiology superimposed on structural damage may contribute to the clinical deficit. Follow-up investigations in a larger sample of age-matched healthy individuals, SA, and PPA patients will be needed to further confirm and extend our findings.