Lesion-symptom Mapping of Acceptability Judgments in Chronic Poststroke Aphasia Reveals the Neurobiological Underpinnings of Receptive Syntax.

Disagreements persist regarding the neural basis of syntactic processing, which has been linked both to inferior frontal and posterior temporal regions of the brain. One focal point of the debate concerns the role of inferior frontal areas in receptive syntactic ability, which is mostly assessed using sentence comprehension involving complex syntactic structures, a task that is potentially confounded with working memory. Syntactic acceptability judgments may provide a better measure of receptive syntax by reducing the need to use high working memory load and complex sentences and by enabling assessment of various types of syntactic violations. We therefore tested the perception of grammatical violations by people with poststroke aphasia (n = 25), along with matched controls (n = 16), using English sentences involving errors in word order, agreement, or subcategorization. Lesion data were also collected. Control participants performed near ceiling in accuracy with higher discriminability of agreement and subcategorization violations than word order; aphasia participants were less able to discriminate violations, but, on average, paralleled control participants discriminability of types of violations. Lesion-symptom mapping showed a correlation between discriminability and posterior temporal regions, but not inferior frontal regions. We argue that these results diverge from models holding that frontal areas are amodal core regions in syntactic structure building and favor models that posit a core hierarchical system in posterior temporal regions.

Bridging the Gap: Association between Objective and Subjective Outcomes of Communication Performance in People with Parkinson's Disease Evaluated for Deep Brain Stimulation.

Background: Decrements in verbal fluency following deep brain stimulation (DBS) in people with Parkinson's disease (PwP) are common. As such, verbal fluency tasks are used in assessing DBS candidacy and target selection. However, the correspondence between testing performance and the patient's perception of communication abilities is not well-established. Methods: The Communication Participation Item Bank (CPIB) was administered to 85 PwP during pre-DBS neuropsychological evaluations. Central tendencies for CPIB responses and correlations between CPIB total scores, clinical and demographic factors, and language-based tasks were examined. Results: Most PwP indicated some degree of communication interference on the CPIB. Worse scores on semantic fluency and greater motor impairment were associated with more communication interference. Conclusions: Our findings suggest an incomplete correspondence between commonly used language-based tests and patient-reported outcomes of communication abilities. The need for a functional communication instrument that reflects the different aspects of communication abilities in functional contexts is emphasized.

Grammatical Parallelism in Aphasia: A Lesion-Symptom Mapping Study.

Sentence structure, or syntax, is potentially a uniquely creative aspect of the human mind. Neuropsychological experiments in the 1970s suggested parallel syntactic production and comprehension deficits in agrammatic Broca's aphasia, thought to result from damage to syntactic mechanisms in Broca's area in the left frontal lobe. This hypothesis was sometimes termed overarching agrammatism, converging with developments in linguistic theory concerning central syntactic mechanisms supporting language production and comprehension. However, the evidence supporting an association among receptive syntactic deficits, expressive agrammatism, and damage to frontal cortex is equivocal. In addition, the relationship among a distinct grammatical production deficit in aphasia, paragrammatism, and receptive syntax has not been assessed. We used lesion-symptom mapping in three partially overlapping groups of left-hemisphere stroke patients to investigate these issues: grammatical production deficits in a primary group of 53 subjects and syntactic comprehension in larger sample sizes (N = 130, 218) that overlapped with the primary group. Paragrammatic production deficits were significantly associated with multiple analyses of syntactic comprehension, particularly when incorporating lesion volume as a covariate, but agrammatic production deficits were not. The lesion correlates of impaired performance of syntactic comprehension were significantly associated with damage to temporal lobe regions, which were also implicated in paragrammatism, but not with the inferior and middle frontal regions implicated in expressive agrammatism. Our results provide strong evidence against the overarching agrammatism hypothesis. By contrast, our results suggest the possibility of an alternative grammatical parallelism hypothesis rooted in paragrammatism and a central syntactic system in the posterior temporal lobe.

Predictive Coding and Internal Error Correction in Speech Production.

Speech production involves the careful orchestration of sophisticated systems, yet overt speech errors rarely occur under naturalistic conditions. The present functional magnetic resonance imaging study sought neural evidence for internal error detection and correction by leveraging a tongue twister paradigm that induces the potential for speech errors while excluding any overt errors from analysis. Previous work using the same paradigm in the context of silently articulated and imagined speech production tasks has demonstrated forward predictive signals in auditory cortex during speech and presented suggestive evidence of internal error correction in left posterior middle temporal gyrus (pMTG) on the basis that this area tended toward showing a stronger response when potential speech errors are biased toward nonwords compared to words (Okada et al., 2018). The present study built on this prior work by attempting to replicate the forward prediction and lexicality effects in nearly twice as many participants but introduced novel stimuli designed to further tax internal error correction and detection mechanisms by biasing speech errors toward taboo words. The forward prediction effect was replicated. While no evidence was found for a significant difference in brain response as a function of lexical status of the potential speech error, biasing potential errors toward taboo words elicited significantly greater response in left pMTG than biasing errors toward (neutral) words. Other brain areas showed preferential response for taboo words as well but responded below baseline and were less likely to reflect language processing as indicated by a decoding analysis, implicating left pMTG in internal error correction.

Comparing the brain-behaviour relationship in acute and chronic stroke aphasia.

In stroke aphasia, lesion volume is typically associated with aphasia severity. Although this relationship is likely present throughout recovery, different factors may affect lesion volume and behaviour early into recovery (acute) and in the later stages of recovery (chronic). Therefore, studies typically separate patients into two groups (acute/chronic), and this is often accompanied with arguments for and against using data from acute stroke patients over chronic. However, no comprehensive studies have provided strong evidence of whether the lesion-behaviour relationship early in recovery is comparable to later in the recovery trajectory. To that end, we investigated two aims: (i) whether lesion data from acute and chronic patients yield similar results in region-based lesion-symptom mapping analyses and (ii) if models based on one timepoint accurately predict the other. Lesions and aphasia severity scores from acute (N = 63) and chronic (N = 109) stroke survivors with aphasia were entered into separate univariate region-based lesion-symptom mapping analyses. A support vector regression model was trained on lesion data from either the acute or chronic data set to give an estimate of aphasia severity. Four model-based analyses were conducted: trained on acute/chronic using leave-one-out, tested on left-out behaviour or trained on acute/chronic to predict the other timepoint. Region-based lesion-symptom mapping analyses identified similar but not identical regions in both timepoints. All four models revealed positive correlations between actual and predicted Western Aphasia Battery-Revised aphasia-quotient scores. Lesion-to-behaviour predictions were almost equivalent when comparing within versus across stroke stage, despite differing lesion size/locations and distributions of aphasia severity between stroke timepoints. This suggests that research investigating the brain-behaviour relationship including subsets of patients from only one timepoint may also be applicable at other timepoints, although it is important to note that these comparable findings may only be seen using broad measures such as aphasia severity, rather than those aimed at identifying more specific deficits. Subtle differences found between timepoints may also be useful in understanding the nature of lesion volume and aphasia severity over time. Stronger correlations found when predicting acute behaviour (e.g. predicting acute: r = 0.6888, P < 0.001, predicting chronic r = 0.5014, P < 0.001) suggest that the acute lesion/perfusion patterns more accurately capture the critical changes in underlying vascular territories. Differences in critical brain regions between timepoints may shed light on recovery patterns. Future studies could focus on a longitudinal design to compare acute and chronic patients in a more controlled manner.

Beyond Broca: neural architecture and evolution of a dual motor speech coordination system.

Classical neural architecture models of speech production propose a single system centred on Broca's area coordinating all the vocal articulators from lips to larynx. Modern evidence has challenged both the idea that Broca's area is involved in motor speech coordination and that there is only one coordination network. Drawing on a wide range of evidence, here we propose a dual speech coordination model in which laryngeal control of pitch-related aspects of prosody and song are coordinated by a hierarchically organized dorsolateral system while supralaryngeal articulation at the phonetic/syllabic level is coordinated by a more ventral system posterior to Broca's area. We argue further that these two speech production subsystems have distinguishable evolutionary histories and discuss the implications for models of language evolution.

Predicting Outcomes of Language Rehabilitation: Prognostic Factors for Immediate and Long-Term Outcomes After Aphasia Therapy.

BACKGROUND: Aphasia therapy is an effective approach to improve language function in chronic aphasia. However, it remains unclear what prognostic factors facilitate therapy response at the individual level. Here, we utilized data from the POLAR (Predicting Outcomes of Language Rehabilitation in Aphasia) trial to (a) determine therapy-induced change in confrontation naming and long-term maintenance of naming gains and (b) examine the extent to which aphasia severity, age, education, time postonset, and cognitive reserve predict naming gains at 1 week, 1 month, and 6 months posttherapy. METHOD: A total of 107 participants with chronic (≥ 12 months poststroke) aphasia underwent extensive case history, cognitive-linguistic testing, and a neuroimaging workup prior to receiving 6 weeks of impairment-based language therapy. Therapy-induced change in naming performance (measured as raw change on the 175-item Philadelphia Naming Test [PNT]) was assessed 1 week after therapy and at follow-up time points 1 month and 6 months after therapy completion. Change in naming performance over time was evaluated using paired t tests, and linear mixed-effects models were constructed to examine the association between prognostic factors and therapy outcomes. RESULTS: Naming performance was improved by 5.9 PNT items (Cohen's d = 0.56, p < .001) 1 week after therapy and by 6.4 (d = 0.66, p < .001) and 7.5 (d = 0.65, p < .001) PNT items at 1 month and 6 months after therapy completion, respectively. Aphasia severity emerged as the strongest predictor of naming improvement recovery across time points; mild (ß = 5.85-9.02) and moderate (ß = 9.65-11.54) impairment predicted better recovery than severe (ß = 1.31-3.37) and very severe (ß = 0.20-0.32) aphasia. Age was an emergent prognostic factor for recovery 1 month (ß = -0.14) and 6 months (ß = -0.20) after therapy, and time postonset (ß = -0.05) was associated with retention of naming gains at 6 months posttherapy. CONCLUSIONS: These results suggest that therapy-induced naming improvement is predictable based on several easily measurable prognostic factors. Broadly speaking, these results suggest that prognostication procedures in aphasia therapy can be improved and indicate that personalization of therapy is a realistic goal in the near future. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.22141829.

Forward entrainment: Psychophysics, neural correlates, and function.

We define forward entrainment as that part of behavioral or neural entrainment that outlasts the entraining stimulus. In this review, we examine conditions under which one may optimally observe forward entrainment. In Part 1, we review and evaluate studies that have observed forward entrainment using a variety of psychophysical methods (detection, discrimination, and reaction times), different target stimuli (tones, noise, and gaps), different entraining sequences (sinusoidal, rectangular, or sawtooth waveforms), a variety of physiological measures (MEG, EEG, ECoG, CSD), in different modalities (auditory and visual), across modalities (audiovisual and auditory-motor), and in different species. In Part 2, we describe those experimental conditions that place constraints on the magnitude of forward entrainment, including an evaluation of the effects of signal uncertainty and attention, temporal envelope complexity, signal-to-noise ratio (SNR), rhythmic rate, prior experience, and intersubject variability. In Part 3 we theorize on potential mechanisms and propose that forward entrainment may instantiate a dynamic auditory afterimage that lasts a fraction of a second to minimize prediction error in signal processing.

Informational Masking in Aging and Brain-lesioned Individuals.

Auditory stream segregation and informational masking were investigated in brain-lesioned individuals, age-matched controls with no neurological disease, and young college-age students. A psychophysical paradigm known as rhythmic masking release (RMR) was used to examine the ability of participants to identify a change in the rhythmic sequence of 20-ms Gaussian noise bursts presented through headphones and filtered through generalized head-related transfer functions to produce the percept of an externalized auditory image (i.e., a 3D virtual reality sound). The target rhythm was temporally interleaved with a masker sequence comprising similar noise bursts in a manner that resulted in a uniform sequence with no information remaining about the target rhythm when the target and masker were presented from the same location (an impossible task). Spatially separating the target and masker sequences allowed participants to determine if there was a change in the target rhythm midway during its presentation. RMR thresholds were defined as the minimum spatial separation between target and masker sequences that resulted in 70.7% correct-performance level in a single-interval 2-alternative forced-choice adaptive tracking procedure. The main findings were (1) significantly higher RMR thresholds for individuals with brain lesions (especially those with damage to parietal areas) and (2) a left-right spatial asymmetry in performance for lesion (but not control) participants. These findings contribute to a better understanding of spatiotemporal relations in informational masking and the neural bases of auditory scene analysis.

Detection of dynamic changes in interaural delay by older adults (L).

The ability of older adults (48 to 72) with relatively intact low-frequency hearing to detect the motion of an acoustic source was investigated using dynamically varying interaural delays. Thresholds were measured using a single-interval two-alternative forced-choice task in which listeners determined if the sound source was moving or stationary. Motion thresholds were significantly larger than stationary localization thresholds. No correlation was observed between age and motion-detection ability for the age range tested. An interesting finding was that there were similar thresholds for older and younger adults. Results suggest reliance on dominant low-frequency binaural timing cues unaffected by high-frequency hearing loss in older adults.

The Severity-Calibrated Aphasia Naming Test.

PURPOSE: We present a 20-item naming test, the Severity-Calibrated Aphasia Naming Test (SCANT), that can serve as a proxy measure for an aphasia severity scale that is derived from a thorough test battery of connected speech production, single-word production, speech repetition, and auditory verbal comprehension. METHOD: We use lasso regression and cross-validation to identify an optimal subset from a set of 174 pictures to be named for prediction of aphasia severity, based on data from 200 participants with left-hemisphere stroke who were quasirandomly selected to represent the full impairment scale. Data from 20 healthy controls (i.e., participant caretakers/spouses) were also analyzed. We examine interrater reliability, test-retest reliability, sensitivity and specificity to the presence of aphasia, sensitivity to therapy gains, and external validity (i.e., correlation with aphasia severity measures) for the SCANT. RESULTS: The SCANT has extremely high interrater reliability, and it is sensitive and specific to the presence of aphasia. We demonstrate the superiority of predictions based on the SCANT over those based on the full set of naming items. We estimate a 15% reduction in power when using the SCANT score versus the full test battery's aphasia severity score as an outcome measure; for example, to maintain the same power to detect a significant group average change in aphasia severity, a study with 25 participants using the full test battery to measure treatment effectiveness would require 30 participants if the SCANT were to be used as the testing instrument instead. CONCLUSION: We provide a linear model to convert SCANT scores to aphasia severity scores, and we identify a change score cutoff of four SCANT items to obtain a high degree of confidence based on test-retest SCANT data and the modeled relation between SCANT and aphasia severity scores. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.21476871.

Confirming an antiphasic bicyclic pattern of forward entrainment in signal detection: A reanalysis of Sun et al. (2021).

Forward entrainment refers to that part of the entrainment process that persists after termination of an entraining stimulus. Hickok et al. (2015) reported forward entrainment in signal detection that lasted for two post-stimulus cycles. In a recent paper, Sun et al. (2021) reported new data which suggested an absence of entrainment effects (Eur. J. Neurosci, 1-18, doi.org/10.1111/ejn.15367). Here we show that when Sun et al.'s data are analysed using unbiased detection-theoretic measures, a clear antiphasic bicyclic pattern of entrainment is observed. We further show that the measure of entrainment strength used by Sun et al., the normalized Fourier transform of performance curves, is not only erroneously calculated but is also unreliable in estimating entrainment strength due to signal-processing artifacts.

Predictors beyond the lesion: Health and demographic factors associated with aphasia severity.

BACKGROUND: Lesion-related factors are associated with severity of language impairment in persons with aphasia. The extent to which demographic and health factors predict language impairment beyond traditional cortical measures remains unknown. Identifying and understanding the contributions of factors to predictive models of severity constitutes critical knowledge for clinicians interested in charting the likely course of aphasia in their patients and designing effective treatment approaches in light of those predictions. METHODS: Utilizing neuroimaging and language testing from our cohort of 224 individuals in the chronic stage of recovery from a left-hemisphere stroke in a cross-sectional study, we first conducted a lesion symptom mapping (LSM) analysis to identify regions associated with aphasia severity scores. After controlling for lesion volume and damage to pre-identified areas, three models were created to predict severity scores: 1) Demographic Model (N = 147); 2) Health Model (N = 106); and 3) Overall Model (N = 106). Finally, all identified factors were entered into a Final Model to predict raw severity scores. RESULTS: Two areas were associated with aphasia severity-left posterior insula and left arcuate fasciculus. The results from the Demographic Model revealed non-linguistic cognitive ability, age at stroke, and time post-stroke as significant predictors of severity (P = .005; P = .02; P = .001, respectively), and results from the Health Model suggested the extent of leukoaraiosis is associated with severity (P = .0004). The Overall Model showed a relationship between aphasia severity and cognitive ability (P = .01), time post-stroke (P = .002), and leukoaraiosis (P = .01). In the Final Model, which aimed to predict raw severity scores, demographic, health, and lesion factors explained 55% of the variance in severity, with health and demographic factors uniquely explaining nearly half of performance variance. CONCLUSIONS: Results from this study add to the literature suggesting patient-specific variables can shed light on individual differences in severity beyond lesion factors. Additionally, our results emphasize the importance of non-linguistic cognitive ability and brain health in aphasia recovery.

A critical analysis of Lin et al.'s (2021) failure to observe forward entrainment in pitch discrimination.

Forward entrainment refers to that part of the entrainment process that outlasts the entraining stimulus. Several studies have demonstrated psychophysical forward entrainment in a pitch-discrimination task. In a recent paper, Lin et al. (2021) challenged these findings by demonstrating that a sequence of 4 entraining pure tones does not affect the ability to determine whether a frequency modulated pulse, presented after termination of the entraining sequence, has swept up or down in frequency. They concluded that rhythmic sequences do not facilitate pitch discrimination. Here, we describe several methodological and stimulus design flaws in Lin et al.'s study that may explain their failure to observe forward entrainment in pitch discrimination.

Inadequate pitch-difference sensitivity prevents half of all listeners from discriminating major vs minor tone sequences.

Substantial evidence suggests that sensitivity to the difference between the major vs minor musical scales may be bimodally distributed. Much of this evidence comes from experiments using the "3-task." On each trial in the 3-task, the listener hears a rapid, random sequence of tones containing equal numbers of notes of either a G major or G minor triad and strives (with feedback) to judge which type of "tone-scramble" it was. This study asks whether the bimodal distribution in 3-task performance is due to variation (across listeners) in sensitivity to differences in pitch. On each trial in a "pitch-difference task," the listener hears two tones and judges whether the second tone is higher or lower than the first. When the first tone is roved (rather than fixed throughout the task), performance varies dramatically across listeners with median threshold approximately equal to a quarter-tone. Strikingly, nearly all listeners with thresholds higher than a quarter-tone performed near chance in the 3-task. Across listeners with thresholds below a quarter-tone, 3-task performance was uniformly distributed from chance to ceiling; thus, the large, lower mode of the distribution in 3-task performance is produced mainly by listeners with roved pitch-difference thresholds greater than a quarter-tone.

The Wernicke conundrum revisited: evidence from connectome-based lesion-symptom mapping.

Wernicke's area has been assumed since the 1800s to be the primary region supporting word and sentence comprehension. However, in 2015 and 2019, Mesulam and colleagues raised what they termed the 'Wernicke conundrum', noting widespread variability in the anatomical definition of this area and presenting data from primary progressive aphasia that challenged this classical assumption. To resolve the conundrum, they posited a 'double disconnection' hypothesis: that word and sentence comprehension deficits in stroke-based aphasia result from disconnection of anterior temporal and inferior frontal regions from other parts of the brain due to white matter damage, rather than dysfunction of Wernicke's area itself. To test this hypothesis, we performed lesion-deficit correlations, including connectome-based lesion-symptom mapping, in four large, partially overlapping groups of English-speaking chronic left hemisphere stroke survivors. After removing variance due to object recognition and associative semantic processing, the same middle and posterior temporal lobe regions were implicated in both word comprehension deficits and complex non-canonical sentence comprehension deficits. Connectome lesion-symptom mapping revealed similar temporal-occipital white matter disconnections for impaired word and non-canonical sentence comprehension, including the temporal pole. We found an additional significant temporal-parietal disconnection for non-canonical sentence comprehension deficits, which may indicate a role for phonological working memory in processing complex syntax, but no significant frontal disconnections. Moreover, damage to these middle-posterior temporal lobe regions was associated with both word and non-canonical sentence comprehension deficits even when accounting for variance due to the strongest anterior temporal and inferior frontal white matter disconnections, respectively. Our results largely agree with the classical notion that Wernicke's area, defined here as middle superior temporal gyrus and middle-posterior superior temporal sulcus, supports both word and sentence comprehension, suggest a supporting role for temporal pole in both word and sentence comprehension, and speak against the hypothesis that comprehension deficits in Wernicke's aphasia result from double disconnection.

The Neuroanatomy of Speech Processing: A Large-scale Lesion Study.

The neural basis of language has been studied for centuries, yet the networks critically involved in simply identifying or understanding a spoken word remain elusive. Several functional-anatomical models of critical neural substrates of receptive speech have been proposed, including (1) auditory-related regions in the left mid-posterior superior temporal lobe, (2) motor-related regions in the left frontal lobe (in normal and/or noisy conditions), (3) the left anterior superior temporal lobe, or (4) bilateral mid-posterior superior temporal areas. One difficulty in comparing these models is that they often focus on different aspects of the sound-to-meaning pathway and are supported by different types of stimuli and tasks. Two auditory tasks that are typically used in separate studies-syllable discrimination and word comprehension-often yield different conclusions. We assessed syllable discrimination (words and nonwords) and word comprehension (clear speech and with a noise masker) in 158 individuals with focal brain damage: left (n = 113) or right (n = 19) hemisphere stroke, left (n = 18) or right (n = 8) anterior temporal lobectomy, and 26 neurologically intact controls. Discrimination and comprehension tasks are doubly dissociable both behaviorally and neurologically. In support of a bilateral model, clear speech comprehension was near ceiling in 95% of left stroke cases and right temporal damage impaired syllable discrimination. Lesion-symptom mapping analyses for the syllable discrimination and noisy word comprehension tasks each implicated most of the left superior temporal gyrus. Comprehension but not discrimination tasks also implicated the left posterior middle temporal gyrus, whereas discrimination but not comprehension tasks also implicated more dorsal sensorimotor regions in posterior perisylvian cortex.

Neural correlates of impaired vocal feedback control in post-stroke aphasia.

We used left-hemisphere stroke as a model to examine how damage to sensorimotor brain networks impairs vocal auditory feedback processing and control. Individuals with post-stroke aphasia and matched neurotypical control subjects vocalized speech vowel sounds and listened to the playback of their self-produced vocalizations under normal (NAF) and pitch-shifted altered auditory feedback (AAF) while their brain activity was recorded using electroencephalography (EEG) signals. Event-related potentials (ERPs) were utilized as a neural index to probe the effect of vocal production on auditory feedback processing with high temporal resolution, while lesion data in the stroke group was used to determine how brain abnormality accounted for the impairment of such mechanisms. Results revealed that ERP activity was aberrantly modulated during vocalization vs. listening in aphasia, and this effect was accompanied by the reduced magnitude of compensatory vocal responses to pitch-shift alterations in the auditory feedback compared with control subjects. Lesion-mapping revealed that the aberrant pattern of ERP modulation in response to NAF was accounted for by damage to sensorimotor networks within the left-hemisphere inferior frontal, precentral, inferior parietal, and superior temporal cortices. For responses to AAF, neural deficits were predicted by damage to a distinguishable network within the inferior frontal and parietal cortices. These findings define the left-hemisphere sensorimotor networks implicated in auditory feedback processing, error detection, and vocal motor control. Our results provide translational synergy to inform the theoretical models of sensorimotor integration while having clinical applications for diagnosis and treatment of communication disabilities in individuals with stroke and other neurological conditions.