Listening to narrative speech after aphasic stroke: The role of the left anterior temporal lobe

The dorsal bank of the primate superior temporal sulcus (STS) is a polysensory area with rich connections to unimodal sensory association cortices. These include auditory projections that process complex acoustic information, including conspecific vocalizations. We investigated whether an extensive left posterior temporal (Wernicke’s area) lesion, which included destruction of early auditory cortex, may contribute to impaired spoken narrative comprehension as a consequence of reduced function in the anterior STS, a region not included within the boundary of infarction. Listening to narratives in normal subjects activated the posterior--anterior extent of the left STS, as far forward as the temporal pole. The presence of a Wernicke’s area lesion was associated with both impaired sentence comprehension and a reduced physiological response to heard narratives in the intact anterior left STS when compared to aphasic patients without temporal lobe damage and normal controls. Thus, in addition to the loss of language function in left posterior temporal cortex as the direct result of infarction, posterior ablation that includes primary and early association auditory cortex impairs language function in the intact anterior left temporal lobe. The implication is that clinical studies of language on stroke patients have underestimated the role of left anterior temporal cortex in comprehension of narrative speech

The left superior temporal gyrus is a shared substrate for auditory short-term memory and speech comprehension: evidence from 210 patients with stroke

Competing theories of short-term memory function make specific predictions about the functional anatomy of auditory short-term memory and its role in language comprehension. We analysed high-resolution structural magnetic resonance images from 210 stroke patients and employed a novel voxel based analysis to test the relationship between auditory short-term memory and speech comprehension. Using digit span as an index of auditory short-term memory capacity we found that the structural integrity of a posterior region of the superior temporal gyrus and sulcus predicted auditory short-term memory capacity, even when performance on a range of other measures was factored out. We show that the integrity of this region also predicts the ability to comprehend spoken sentences. Our results therefore support cognitive models that posit a shared substrate between auditory short-term memory capacity and speech comprehension ability. The method applied here will be particularly useful for modelling structure–function relationships within other complex cognitive domains

How does iReadMore therapy change the reading network of patients with central alexia?

Central alexia (CA) is an acquired reading disorder co-occurring with a generalised language deficit (aphasia). The roles of perilesional and ipsilesional tissue in recovery from post-stroke aphasia are unclear. We investigated the impact of reading training (using iReadMore, a therapy app) on the connections within and between the right and left hemisphere of the reading network of patients with CA. In patients with pure alexia, iReadMore increased feedback from left inferior frontal region (IFG) to the left occipital (OCC) region. We aimed to identify if iReadMore therapy was effective through a similar mechanism in CA patients.Participants with chronic post-stroke CA (n=23) completed 35 hours of iReadMore training over four weeks. Reading accuracy for trained and untrained words was assessed before and after therapy. The neural response to reading trained and untrained words in the left and right OCC, ventral occipitotemporal (vOT) and IFG was examined using event-related magnetoencephalography.The training-related modulation in effective connectivity between regions was modelled at the group level with Dynamic Causal Modelling.iReadMore training improved participants' reading accuracy by an average of 8.4% (range: -2.77 to 31.66) while accuracy for untrained words was stable. Training increased regional sensitivity in bilateral frontal and occipital regions, and strengthened feedforward connections within the left hemisphere. Our data suggests that iReadMore training in these patients modulates lower-order visual representations, as opposed to higher-order, more abstract ones, in order to improve word reading accuracy.SIGNIFICANCE STATEMENTThis is the first study to conduct a network-level analyses of therapy effects in participants with post-stroke central alexia. When patients trained with iReadMore (a multimodal, behavioural, mass practice, computer-based therapy), reading accuracy improved by an average 8.4% on trained items. A network analysis of the magnetoencephalography data associated with this improvement revealed an increase in regional sensitivity in bilateral frontal and occipital regions and strengthening of feedforward connections within the left hemisphere. This indicates that in CA patients iReadMore engages lower-order, intact resources within the left hemisphere (posterior to their lesion locations) to improve word reading. This provides a foundation for future research to investigate reading network modulation in different CA subtypes, or for sentence level therapy

Predicting Online Behavioural Responses to Transcranial Direct Current Stimulation in Stroke Patients with Anomia

Anomia, or difficulty naming common objects, is the most common, acquired impairment of language. Effective therapeutic interventions for anomia typically involve massed practice at high doses. This requires significant investment from patients and therapists. Aphasia researchers have increasingly looked to neurostimulation to accelerate these treatment effects, but the evidence behind this intervention is sparse and inconsistent. Here, we hypothesised that group-level neurostimulation effects might belie a more systematic structure at the individual level. We sought to test the hypothesis by attempting to predict the immediate (online), individual-level behavioural effects of anodal and sham neurostimulation in 36 chronic patients with anomia, performing naming and size judgement tasks. Using clinical, (pre-stimulation) behavioural and MRI data, as well as Partial Least Squares regression, we attempted to predict neurostimulation effects on accuracies and reaction times of both tasks. Model performance was assessed via cross-validation. Predictive performances were compared to that of a null model, which predicted the mean neurostimulation effects for all patients. Models derived from pre-stimulation data consistently outperformed the null model when predicting neurostimulation effects on both tasks’ performance. Notably, we could predict behavioural declines just as well as improvements. In conclusion, inter-patient variation in online responses to neurostimulation is, to some extent, systematic and predictable. Since declines in performance were just as predictable as improvements, the behavioural effects of neurostimulation in patients with anomia are unlikely to be driven by placebo effects. However, the online effect of the intervention appears to be as likely to interfere with task performance as to improve it

Predicting online behavioural responses to transcranial direct current stimulation in stroke patients with anomia

Anomia, or difficulty naming common objects, is the most common, acquired impairment of language. Effective therapeutic interventions for anomia typically involve massed practice at high doses. This requires significant investment from patients and therapists. Aphasia researchers have increasingly looked to neurostimulation to accelerate these treatment effects, but the evidence behind this intervention is sparse and inconsistent. Here, we hypothesised that group-level neurostimulation effects might belie a more systematic structure at the individual level. We sought to test the hypothesis by attempting to predict the immediate (online), individual-level behavioural effects of anodal and sham neurostimulation in 36 chronic patients with anomia, performing naming and size judgement tasks. Using clinical, (pre-stimulation) behavioural and MRI data, as well as Partial Least Squares regression, we attempted to predict neurostimulation effects on accuracies and reaction times of both tasks. Model performance was assessed via cross-validation. Predictive performances were compared to that of a null model, which predicted the mean neurostimulation effects for all patients. Models derived from pre-stimulation data consistently outperformed the null model when predicting neurostimulation effects on both tasks’ performance. Notably, we could predict behavioural declines just as well as improvements. In conclusion, inter-patient variation in online responses to neurostimulation is, to some extent, systematic and predictable. Since declines in performance were just as predictable as improvements, the behavioural effects of neurostimulation in patients with anomia are unlikely to be driven by placebo effects. However, the online effect of the intervention appears to be as likely to interfere with task performance as to improve it

Less is more: neural mechanisms underlying anomia treatment in chronic aphasic patients.

Previous research with aphasic patients has shown that picture naming can be facilitated by concurrent phonemic cueing [e.g.initial phoneme(s) of the word that the patient is trying to retrieve], both as an immediate word retrieval technique, and when practiced repeatedly over time as a long-term anomia treatment. Here, to investigate the neural mechanisms supporting word retrieval, we adopted—for the first time—a functional magnetic resonance imaging task using the same naming procedure as it occurs during the anomia treatment process. Before and directly after a 6-week anomia treatment programme, 18 chronic aphasic stroke patients completed our functional magnetic resonance imaging protocol—a picture naming task aided by three different types of phonemic cues (whole words, initial phonemes, final phonemes) and a noise-control condition. Patients completed a naming task based on the training materials, and a more general comprehensive battery of language tests both before and after the anomia treatment, to determine the effectiveness and specificity of the therapy. Our results demonstrate that the anomia treatment was effective and specific to speech production, significantly improving both patients’ naming accuracy and reaction time immediately post-treatment (unstandardized effect size: 29% and 17%, respectively; Cohen’s d: 3.45 and 1.83). Longer term gains in naming were maintained 3 months later. Functional imaging results showed that both immediate and long-term facilitation of naming involved a largely overlapping bilateral frontal network including the right anterior insula, inferior frontal and dorsal anterior cingulate cortices, and the left premotor cortex. These areas were associated with a neural priming effect (i.e. reduced blood oxygen level-dependent signal) during both immediate (phonemically-cued versus control-cue conditions), and long-term facilitation of naming (i.e. treated versus untreated items). Of note is that different brain regions were sensitive to different phonemic cue types. Processing of whole word cues was associated with increased activity in the right angular gyrus; whereas partial word cues (initial and final phonemes) recruited the left supplementary motor area, and right anterior insula, inferior frontal cortex, and basal ganglia. The recruitment of multiple and bilateral areas may help explain why phonemic cueing is such a successful behavioural facilitation tool for anomia treatment. Our results have important implications for optimizing current anomia treatment approaches, developing new treatments, and improving speech outcome for aphasic patient

Damage to Broca’s area does not contribute to long-term speech production outcome after stroke

Broca’s area in the posterior half of the left inferior frontal gyrus has long been thought to be critical for speech production. The current view is that long-term speech production outcome in patients with Broca’s area damage is best explained by the combination of damage to Broca’s area and neighbouring regions including the underlying white matter, which was also damaged in Paul Broca’s two historic cases. Here, we dissociate the effect of damage to Broca’s area from the effect of damage to surrounding areas by studying long-term speech production outcome in 134 stroke survivors with relatively circumscribed left frontal lobe lesions that spared posterior speech production areas in lateral inferior parietal and superior temporal association cortices. Collectively, these patients had varying degrees of damage to one or more of nine atlas-based grey or white matter regions: Brodmann areas 44 and 45 (together known as Broca’s area), ventral premotor cortex, primary motor cortex, insula, putamen, the anterior segment of the arcuate fasciculus, uncinate fasciculus and frontal aslant tract. Spoken picture description scores from the ComprehensiveAphasia Test were used as the outcome measure. Multiple regression analyses allowed us to tease apart the contribution of other variables influencing speech production abilities such as total lesion volume and time post-stroke. We found that, in our sample of patients with left frontal damage, long-term speech production impairments (lasting beyond 3 months post-stroke) were solely predictedby the degree of damage to white matter, directly above the insula, in the vicinity of the anterior part of the arcuate fasciculus, with no contribution from the degree of damage to Broca’s area (as confirmed with Bayesian statistics). The effect of white matter damage cannot be explained by a disconnection of Broca’s area, because speech production scores were worse after damage to the anterior arcuate fasciculus with relative sparing of Broca’s area than after damage to Broca’s area with relative sparing of the anterior arcuate fasciculus. Our findings provide evidence for three novel conclusions: (i) Broca’s area damage does not contribute to long-term speech production outcome after left frontal lobe strokes; (ii) persistent speech production impairments after damage to the anterior arcuate fasciculus cannot be explained by a disconnection of Broca’s area; and (iii) the prior association between persistent speech production impairments and Broca’s area damage can be explained by co-occurring white matter damage, above the insula, in the vicinity of the anterior part of the arcuate fasciculus

How distributed processing produces false negatives in voxel-based lesion-deficit analyses

In this study, we hypothesized that if the same deficit can be caused by damage to one or another part of a distributed neural system, then voxel-based analyses might miss critical lesion sites because preservation of each site will not be consistently associated with preserved function. The first part of our investigation used voxelbased multiple regression analyses of data from 359 right-handed stroke survivors to identify brain regions where lesion load is associated with picture naming abilities after factoring out variance related to object recognition, semantics and speech articulation so as to focus on deficits arising at the word retrieval level. A highly significant lesion-deficit relationship was identified in left temporal and frontal/premotor regions. Post-hoc analyses showed that damage to either of these sites caused the deficit of interest in less than half the affected patients (76/162 = 47%). After excluding all patients with damage to one or both of the identified regions, our second analysis revealed a new region, in the anterior part of the left putamen, which had not been previously detected because many patients had the deficit of interest after temporal or frontal damage that preserved the left putamen. The results illustrate how (i) false negative results arise when the same deficit can be caused by different lesion sites; (ii) some of the missed effects can be unveiled by adopting an iterative approach that systematically excludes patients with lesions to the areas identified in previous analyses, (iii) statistically significant voxel-based lesion-deficit mappings can be driven by a subset of patients; (iv) focal lesions to the identified regions are needed to determine whether the deficit of interest is the consequence of focal damage or much more extensive damage that includes the identified region; and, finally, (v) univariate voxel-based lesiondeficit mappings cannot, in isolation, be used to predict outcome in other patients

Anterior temporal lobe connectivity correlates with functional outcome after aphasic stroke

Focal brain lesions are assumed to produce language deficits by two basic mechanisms: local cortical dysfunction at the lesion site, and remote cortical dysfunction due to disruption of the transfer and integration of information between connected brain regions. However, functional imaging studies investigating language outcome after aphasic stroke have tended to focus only on the role of local cortical function. In this positron emission tomography functional imaging study, we explored relationships between language comprehension performance after aphasic stroke and the functional connectivity of a key speech-processing region in left anterolateral superior temporal cortex. We compared the organization of left anterolateral superior temporal cortex functional connections during narrative speech comprehension in normal subjects with left anterolateral superior temporal cortex connectivity in a group of chronic aphasic stroke patients. We then evaluated the language deficits associated with altered left anterolateral superior temporal cortex connectivity in aphasic stroke. During normal narrative speech comprehension, left anterolateral superior temporal cortex displayed positive functional connections with left anterior basal temporal cortex, left inferior frontal gyrus and homotopic cortex in right anterolateral superior temporal cortex. As a group, aphasic patients demonstrated a selective disruption of the normal functional connection between left and right anterolateral superior temporal cortices. We observed that deficits in auditory single word and sentence comprehension correlated both with the degree of disruption of left-right anterolateral superior temporal cortical connectivity and with local activation in the anterolateral superior temporal cortex. Subgroup analysis revealed that aphasic patients with preserved positive intertemporal connectivity displayed better receptive language function; these patients also showed greater than normal left inferior frontal gyrus activity, suggesting a possible ‘top-down’ compensatory mechanism. These results demonstrate that functional connectivity between anterolateral superior temporal cortex and right anterior superior temporal cortex is a marker of receptive language outcome after aphasic stroke, and illustrate that language system organization after focal brain lesions may be marked by complex signatures of altered local and pathway-level function