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.

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.

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.

Functional differentiation in the language network revealed by lesion-symptom mapping.

Theories of language organization in the brain commonly posit that different regions underlie distinct linguistic mechanisms. However, such theories have been criticized on the grounds that many neuroimaging studies of language processing find similar effects across regions. Moreover, condition by region interaction effects, which provide the strongest evidence of functional differentiation between regions, have rarely been offered in support of these theories. Here we address this by using lesion-symptom mapping in three large, partially-overlapping groups of aphasia patients with left hemisphere brain damage due to stroke (N = 121, N = 92, N = 218). We identified multiple measure by region interaction effects, associating damage to the posterior middle temporal gyrus with syntactic comprehension deficits, damage to posterior inferior frontal gyrus with expressive agrammatism, and damage to inferior angular gyrus with semantic category word fluency deficits. Our results are inconsistent with recent hypotheses that regions of the language network are undifferentiated with respect to high-level linguistic processing.

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.

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.

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.

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.

Isolating the white matter circuitry of the dorsal language stream: Connectome-Symptom Mapping in stroke induced aphasia.

The application of ℓ1-regularized machine learning models to high-dimensional connectomes offers a promising methodology to assess clinical-anatomical correlations in humans. Here, we integrate the connectome-based lesion-symptom mapping framework with sparse partial least squares regression (sPLS-R) to isolate elements of the connectome associated with speech repetition deficits. By mapping over 2,500 connections of the structural connectome in a cohort of 71 stroke-induced cases of aphasia presenting with varying left-hemisphere lesions and repetition impairment, sPLS-R was trained on 50 subjects to algorithmically identify connectomic features on the basis of their predictive value. The highest ranking features were subsequently used to generate a parsimonious predictive model for speech repetition whose predictions were evaluated on a held-out set of 21 subjects. A set of 10 short- and long-range parieto-temporal connections were identified, collectively delineating the broader circuitry of the dorsal white matter network of the language system. The strongest contributing feature was a short-range connection in the supramarginal gyrus, approximating the cortical localization of area Spt, with parallel long-range pathways interconnecting posterior nodes in supramarginal and superior temporal cortex with anterior nodes in both ventral and-notably-in dorsal premotor cortex, respectively. The collective disruption of these pathways indexed repetition performance in the held-out set of participants, suggesting that these impairments might be characterized as a parietotemporal disconnection syndrome impacting cortical area Spt and its associated white matter circuits of the frontal lobe as opposed to being purely a disconnection of the arcuate fasciculus.

Connections and selections: Comparing multivariate predictions and parameter associations from latent variable models of picture naming.

Connectionist simulation models and processing tree mathematical models of picture naming have complementary advantages and disadvantages. These model types were compared in terms of their predictions of independent language measures and their associations between model components and measures that should be related according to their theoretical interpretations. The models were tasked with predicting independent picture naming data, neuropsychological test scores of semantic association and speech production, grammatical categories of formal errors, and lexical properties of target items. In all cases, the processing tree model parameters provided better predictions and stronger associations between parameters and independent language measures than the connectionist simulation model. Given the enhanced generalizability of latent variable measurements afforded by the processing tree model, evidence regarding mechanistic and representational features of the speech production system are re-evaluated. Several areas are indicated as being potentially viable targets for elaboration of the mechanistic descriptions of picture naming errors.

A double dissociation between plural and possessive "s": Evidence from the Morphosyntactic Generation test.

People with aphasia demonstrate impaired production of bound inflectional morphemes, such as noun plurals and possession. They often show greater difficulty in marking possession versus plurality. Using a new tool for eliciting language, the Morphosyntactic Generation test, we assessed people with primary progressive aphasia and those in the acute and chronic phase following left hemisphere stroke. Clinical profiles were associated with different strengths and weaknesses in language production. Performance of the plural was stronger than possessive in group analyses. However, some individuals demonstrated the inverse pattern of performance. These participants provide counter-evidence to the theory that difficulty with marking possessives is purely the result of their greater cognitive-linguistic complexity and support a functional double dissociation between possessives and plurals. The deficits resulted from morphosyntactic impairment. Future work is needed to understand why plural and possessive markers were differently sensitive to neurological disorders of language.

The Cortical Organization of Syntax.

Syntax, the structure of sentences, enables humans to express an infinite range of meanings through finite means. The neurobiology of syntax has been intensely studied but with little consensus. Two main candidate regions have been identified: the posterior inferior frontal gyrus (pIFG) and the posterior middle temporal gyrus (pMTG). Integrating research in linguistics, psycholinguistics, and neuroscience, we propose a neuroanatomical framework for syntax that attributes distinct syntactic computations to these regions in a unified model. The key theoretical advances are adopting a modern lexicalized view of syntax in which the lexicon and syntactic rules are intertwined, and recognizing a computational asymmetry in the role of syntax during comprehension and production. Our model postulates a hierarchical lexical-syntactic function to the pMTG, which interconnects previously identified speech perception and conceptual-semantic systems in the temporal and inferior parietal lobes, crucial for both sentence production and comprehension. These relational hierarchies are transformed via the pIFG into morpho-syntactic sequences, primarily tied to production. We show how this architecture provides a better account of the full range of data and is consistent with recent proposals regarding the organization of phonological processes in the brain.

Examining vocal attractiveness through articulatory working space.

Robust gender differences exist in the acoustic correlates of clearly articulated speech, with females, on average, producing speech that is acoustically and phonetically more distinct than that of males. This study investigates the relationship between several acoustic correlates of clear speech and subjective ratings of vocal attractiveness. Talkers were recorded producing vowels in /bVd/ context and sentences containing the four corner vowels. Multiple measures of working vowel space were computed from continuously sampled formant trajectories and were combined with measures of speech timing known to co-vary with clear articulation. Partial least squares regression (PLS-R) modeling was used to predict ratings of vocal attractiveness for male and female talkers based on the acoustic measures. PLS components that loaded on size and shape measures of working vowel space-including the quadrilateral vowel space area, convex hull area, and bivariate spread of formants-along with measures of speech timing were highly successful at predicting attractiveness in female talkers producing /bVd/ words. These findings are consistent with a number of hypotheses regarding human attractiveness judgments, including the role of sexual dimorphism in mate selection, the significance of traits signalling underlying health, and perceptual fluency accounts of preferences.

Brain Damage Associated with Impaired Sentence Processing in Acute Aphasia.

Left-hemisphere brain damage commonly affects patients' abilities to produce and comprehend syntactic structures, a condition typically referred to as "agrammatism." The neural correlates of agrammatism remain disputed in the literature, and distributed areas have been implicated as important predictors of performance, for example, Broca's area, anterior temporal areas, and temporo-parietal areas. We examined the association between damage to specific language-related ROIs and impaired syntactic processing in acute aphasia. We hypothesized that damage to the posterior middle temporal gyrus, and not Broca's area, would predict syntactic processing abilities. One hundred four individuals with acute aphasia (<20 days poststroke) were included in the study. Structural MRI scans were obtained, and all participants completed a 45-item sentence-picture matching task. We performed an ROI-based stepwise regression analyses to examine the relation between cortical brain damage and impaired comprehension of canonical and noncanonical sentences. Damage to the posterior middle temporal gyrus was the strongest predictor for overall task performance and performance on noncanonical sentences. Damage to the angular gyrus was the strongest predictor for performance on canonical sentences, and damage to the posterior superior temporal gyrus predicted noncanonical scores when performance on canonical sentences was included as a cofactor. Overall, our models showed that damage to temporo-parietal and posterior temporal areas was associated with impaired syntactic comprehension. Our results indicate that the temporo-parietal area is crucially implicated in complex syntactic processing, whereas the role of Broca's area may be complementary.

Neural structures supporting spontaneous and assisted (entrained) speech fluency.

Non-fluent speech is one of the most common impairments in post-stroke aphasia. The rehabilitation of non-fluent speech in aphasia is particularly challenging as patients are rarely able to produce and practice fluent speech production. Speech entrainment is a behavioural technique that enables patients with non-fluent aphasia to speak fluently. However, its mechanisms are not well understood and the level of improved fluency with speech entrainment varies among individuals with non-fluent aphasia. In this study, we evaluated the behavioural and neuroanatomical factors associated with better speech fluency with the aid of speech entrainment during the training phase of speech entrainment. We used a lesion-symptom mapping approach to define the relationship between chronic stroke location on MRI and the number of different words per second produced during speech entrainment versus picture description spontaneous speech. The behavioural variable of interest was the speech entrainment/picture description ratio, which, if ≥1, indicated an increase in speech output during speech entrainment compared to picture description. We used machine learning (shallow neural network) to assess the statistical significance and out-of-sample predictive accuracy of the neuroanatomical model, and its regional contributors. We observed that better assisted speech (higher speech entrainment/picture description ratio) was achieved by individuals who had preservation of the posterior middle temporal gyrus, inferior fronto-occipital fasciculus and uncinate fasciculus, while exhibiting lesions in areas typically associated with non-fluent aphasia, such as the superior longitudinal fasciculus, precentral, inferior frontal, supramarginal and insular cortices. Our findings suggest that individuals with dorsal stream damage but preservation of ventral stream structures are more likely to achieve more fluent speech with the aid of speech entrainment compared to spontaneous speech. This observation provides insight into the mechanisms of non-fluent speech in aphasia and has potential implications for future research using speech entrainment for rehabilitation of non-fluent aphasia.

Long-range fibre damage in small vessel brain disease affects aphasia severity.

We sought to determine the underlying pathophysiology relating white matter hyperintensities to chronic aphasia severity. We hypothesized that: (i) white matter hyperintensities are associated with damage to fibres of any length, but to a higher percentage of long-range compared to mid- and short-range intracerebral white matter fibres; and (ii) the number of long-range fibres mediates the relationship between white matter hyperintensities and chronic post-stroke aphasia severity. We measured the severity of periventricular and deep white matter hyperintensities and calculated the number and percentages of short-, mid- and long-range white matter fibres in 48 individuals with chronic post-stroke aphasia. Correlation and mediation analyses were performed to assess the relationship between white matter hyperintensities, connectome fibre-length measures and aphasia severity as measured with the aphasia quotient of the Western Aphasia Battery-Revised (WAB-AQ). We found that more severe periventricular and deep white matter hyperintensities correlated with a lower proportion of long-range fibres (r = -0.423, P = 0.003 and r = -0.315, P = 0.029, respectively), counterbalanced by a higher proportion of short-range fibres (r = 0.427, P = 0.002 and r = 0.285, P = 0.050, respectively). More severe periventricular white matter hyperintensities also correlated with a lower proportion of mid-range fibres (r = -0.334, P = 0.020), while deep white matter hyperintensities did not correlate with mid-range fibres (r = -0.169, P = 0.250). Mediation analyses revealed: (i) a significant total effect of periventricular white matter hyperintensities on WAB-AQ (standardized beta = -0.348, P = 0.008); (ii) a non-significant direct effect of periventricular white matter hyperintensities on WAB-AQ (P > 0.05); (iii) significant indirect effects of more severe periventricular white matter hyperintensities on worse aphasia severity mediated in parallel by fewer long-range fibres (effect = -6.23, bootstrapping: standard error = 2.64, 95%CI: -11.82 to -1.56) and more short-range fibres (effect = 4.50, bootstrapping: standard error = 2.59, 95%CI: 0.16 to 10.29). We conclude that small vessel brain disease seems to affect chronic aphasia severity through a change of the proportions of long- and short-range fibres. This observation provides insight into the pathophysiology of small vessel brain disease, and its relationship with brain health and chronic aphasia severity.

Hierarchy of speech-driven spectrotemporal receptive fields in human auditory cortex.

Existing data indicate that cortical speech processing is hierarchically organized. Numerous studies have shown that early auditory areas encode fine acoustic details while later areas encode abstracted speech patterns. However, it remains unclear precisely what speech information is encoded across these hierarchical levels. Estimation of speech-driven spectrotemporal receptive fields (STRFs) provides a means to explore cortical speech processing in terms of acoustic or linguistic information associated with characteristic spectrotemporal patterns. Here, we estimate STRFs from cortical responses to continuous speech in fMRI. Using a novel approach based on filtering randomly-selected spectrotemporal modulations (STMs) from aurally-presented sentences, STRFs were estimated for a group of listeners and categorized using a data-driven clustering algorithm. 'Behavioral STRFs' highlighting STMs crucial for speech recognition were derived from intelligibility judgments. Clustering revealed that STRFs in the supratemporal plane represented a broad range of STMs, while STRFs in the lateral temporal lobe represented circumscribed STM patterns important to intelligibility. Detailed analysis recovered a bilateral organization with posterior-lateral regions preferentially processing STMs associated with phonological information and anterior-lateral regions preferentially processing STMs associated with word- and phrase-level information. Regions in lateral Heschl's gyrus preferentially processed STMs associated with vocalic information (pitch).

Cortical and structural-connectivity damage correlated with impaired syntactic processing in aphasia.

Agrammatism in aphasia is not a homogeneous syndrome, but a characterization of a nonuniform set of language behaviors in which grammatical markers and complex syntactic structures are omitted, simplified, or misinterpreted. In a sample of 71 left-hemisphere stroke survivors, syntactic processing was quantified with the Northwestern Assessment of Verbs and Sentences (NAVS). Classification analyses were used to assess the relation between NAVS performance and morphosyntactically reduced speech in picture descriptions. Voxel-based and connectivity-based lesion-symptom mapping were applied to investigate neural correlates of impaired syntactic processing. Despite a nonrandom correspondence between NAVS performance and morphosyntactic production deficits, there was variation in individual patterns of syntactic processing. Morphosyntactically reduced production was predicted by lesions to left-hemisphere inferior frontal cortex. Impaired verb argument structure production was predicted by damage to left-hemisphere posterior superior temporal and angular gyrus, as well as to a ventral pathway between temporal and frontal cortex. Damage to this pathway was also predictive of impaired sentence comprehension and production, particularly of noncanonical sentences. Although agrammatic speech production is primarily predicted by lesions to inferior frontal cortex, other aspects of syntactic processing rely rather on regional integrity in temporoparietal cortex and the ventral stream.