Biology subjects

Hickok, G.

Publications and source records attributed to Hickok, G..

12 recordsLinked to original sources

bioRxiv2026

Multiple Nested Distributed Language Networks in the Human Brain

Brain regions specialized for language have been extensively described, yet their arrangement into one or multiple networks remains debated. Using precision functional mapping across three independent cohorts of intensively scanned individuals (22 individuals scanned over 216 separate MRI sessions), we dissociated two nested left-lateralized perisylvian networks: an intermediate language network (intLANG) and an anatomically distinct association language network (aLANG). intLANG is anchored to precentral speech areas and the Sylvian parietal-temporal area (Spt), whereas aLANG surrounds intLANG and extends into higher-order prefrontal and temporal association cortices. The two networks can be fully recapitulated by functional connectivity from adjacent cerebellar regions, indicating that they are segregated, brain-wide networks. Task-based analyses further reveal that intLANG and aLANG are functionally distinct: intLANG responds robustly during rhyme judgments and nonword reading that emphasize phonology, whereas aLANG is preferentially recruited during meaning-based sentence processing. These findings indicate that human language engages nested distributed networks each specialized for distinct components of language processing: a lower-order network biased toward phonology, and a surrounding association network that subserves higher-order syntax and semantics. This nested organization is similar to other brain systems suggesting a shared hierarchical motif that may give rise to specialized cognitive functions across the human brain.

neuroscience↗

bioRxiv2025

Mapping of critical prosodic and phonetic networks in post-stroke apraxia of speech

PurposeMany have made proposals to better diagnose and/or classify post-stroke apraxia of speech (AOS), with some arguing for the separation of AOS into behavioral subtypes. Recent studies of primary progressive AOS have promoted a separation of prosodic and phonetic subtypes, aligning with a dual-motor coordination model separating the neural substrates of prosodic and phonetic function. Motivated by the limited corroboration of these subtypes in post-stroke AOS, here we present mapping results in a cohort of stroke survivors aiming to identify distinct neural substrates for prosodic and phonetic aspects of speech motor coordination. MethodsLeft-hemisphere stroke survivors (n = 127; 64 with AOS) received speech-language evaluation and neuroimaging at the Center for the Study and Treatment of Aphasia Recovery (C-STAR). AOS severity was quantified via the Apraxia of Speech Rating Scale (ASRS). We utilized a novel lesion-symptom mapping technique with an emphasis on prediction that identifies ensembles of regions supporting performance in the prosodic and phonetic domains. ResultsAn ensemble of networks supporting prosodic function localized to dorsal and ventral (but primarily dorsal) sensorimotor cortex, as well as a distributed network of white matter pathways connecting Rolandic cortex to auditory regions and cerebellum, emphasizing the role of auditory feedback processing and laryngeal control in supporting prosodic function. A separate but partially overlapping network supporting phonetic function localized primarily to ventral Rolandic cortex and the arcuate fasciculus. ConclusionsThis work represents the first mapping of prosodic and phonetic subtypes in post-stroke AOS in a large cohort of individuals. We hope our results motivate the development of assessment and treatment techniques individually targeting prosodic and phonetic functioning to better serve individuals with AOS and facilitate clinical discussion of the disorder.

neuroscience↗

bioRxiv2024

Verbal working memory and syntactic comprehension segregate into the dorsal and ventral streams

Syntactic processing and verbal working memory are both essential components to sentence comprehension. Nonetheless, the separability of these systems in the brain remains unclear. To address this issue, we performed causal-inference analyses based on lesion and connectome network mapping using MRI and behavioral testing in 103 individuals with chronic post-stroke aphasia. We employed a rhyme judgment task with heavy working memory load without articulatory confounds, controlling for the overall ability to match auditory words to pictures and to perform a metalinguistic rhyme judgment, isolating the effect of working memory load. We assessed noncanonical sentence comprehension, isolating syntactic processing by incorporating residual rhyme judgment performance as a covariate for working memory load. Voxel-based lesion analyses and structural connectome-based lesion symptom mapping controlling for total lesion volume were performed, with permutation testing to correct for multiple comparisons (4,000 permutations). We observed that effects of working memory load localized to dorsal stream damage: posterior temporal-parietal lesions and frontal-parietal white matter disconnections. These effects were differentiated from syntactic comprehension deficits, which were primarily associated with ventral stream damage: lesions to temporal lobe and temporal-parietal white matter disconnections, particularly when incorporating the residual measure of working memory load as a covariate. Our results support the conclusion that working memory and syntactic processing are associated with distinct brain networks, largely loading onto dorsal and ventral streams, respectively.

neuroscience↗

bioRxiv2024

Cortical networks responsive to phrase structure and subject island violations

In principle, functional neuroimaging provides uniquely informative data in addressing linguistic questions, because it can indicate distinct processes that are not apparent from behavioral data alone. This could involve adjudicating the source of unacceptability via the different patterns of elicited brain responses to different ungrammatical sentence types. However, it is difficult to interpret brain activations to syntactic violations. Such responses could reflect processes that have nothing intrinsically related to linguistic representations, such as domain-general executive function abilities. In order to facilitate the potential use of functional neuroimaging methods to identify the source of different syntactic violations, we conducted an fMRI experiment to identify the brain activation maps associated with two distinct syntactic violation types: phrase structure (created by inverting the order of two adjacent words within a sentence) and subject islands (created by extracting a wh-phrase out of an embedded subject). The comparison of these violations to control sentences surprisingly showed no indication of a generalized violation response, with almost completely divergent activation patterns. Phrase structure violations seemingly activated regions previously implicated in verbal working memory and structural complexity in sentence processing, whereas the subject islands appeared to activate regions previously implicated in conceptual-semantic processing, broadly defined. We review our findings in the context of previous research on syntactic and semantic violations using event- related potentials. Although our results suggest potentially distinct underlying mechanisms underlying phrase structure and subject island violations, our results are tentative and suggest important methodological considerations for future research in this area.

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bioRxiv2021

The Wernicke conundrum revisited: evidence from connectome-based lesion-symptom mapping in post-stroke aphasia

Wernickes area has been assumed since the 1800s to be the primary region supporting word and sentence comprehension. However, Mesulam et al. (2015; 2019) 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 Wernickes area itself. To test this hypothesis, we performed lesiondeficit 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 noncanonical sentence comprehension deficits. Connectome lesion-symptom mapping revealed similar temporal-occipital white matter disconnections for impaired word and noncanonical sentence comprehension, including the temporal pole. We found an additional significant temporal-parietal disconnection for noncanonical 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 noncanonical 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 Wernickes 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 Wernickes aphasia result from double disconnection.

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bioRxiv2021

Forward Entrainment: Evidence, Controversies, Constraints, and Mechanisms

We define forward entrainment as that part of the entrainment process that outlasts the entraining stimulus. In this study, we examine conditions under which one may or may not 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, 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 review those studies that have failed to observe forward entrainment, with emphasis on evaluating the methodological and stimulus design differences that may clarify the contrasting findings across these two classes of studies. In part 3, we describe those experimental conditions under which we ourselves have failed to observe forward entrainment, and provide new data on use of complex envelope patterns as entraining stimuli, show data on intersubject variability, and provide new findings on psychometric functions that characterize the strength of forward entrainment at different SNRs. In part 4 we theorize on potential mechanisms, describe how neurophysiological and psychophysical studies approach the study of entrainment, and caution against drawing direct causal inferences between the two without compelling evidence beyond correlative measures.

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bioRxiv2020

Neuroanatomical dissociations of syntax and semantics 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.

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bioRxiv2020

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), 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 (STG). Comprehension but not discrimination tasks also implicated the left pMTG, while discrimination but not comprehension tasks also implicated more dorsal sensorimotor regions in posterior perisylvian cortex.

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bioRxiv2020

Agrammatism and paragrammatism: a cortical double dissociation revealed by lesion-symptom mapping

The fundamental distinction of grammatical deficits in aphasia, agrammatism and paragrammatism, was made over a century ago. However, the extent to which the agrammatism/paragrammatism distinction exists independently of differences in speech fluency has not clearly been investigated. Despite much research on agrammatism, the lesion correlates of paragrammatism are essentially unknown. Lesion-symptom mapping was used to investigate the degree to which the lesion correlates of agrammatism and paragrammatism overlap or dissociate. Four expert raters assessed videos of 53 right-handed patients with aphasia following chronic left hemisphere stroke retelling the Cinderella story. Consensus discussion determined each subjects classification with respect to grammatical deficits as Agrammatic, Paragrammatic, Both, or No Grammatical Deficit. Each subjects lesion was manually drawn on a high-resolution MRI and warped to standard space for group analyses. Lesion-symptom mapping analyses were performed in NiiStat including lesion volume as a covariate. Secondary analyses included speech rate (words per minute) as an additional covariate. Region of interest analyses identified a double dissociation between these syndromes: damage to Brocas area was significantly associated with agrammatism, p = 0.001 (but not paragrammatism, p = 0.930), while damage to the left posterior superior and middle temporal gyri was significantly associated with paragrammatism, p < 0.001 (but not agrammatism, p = 0.873). The same results obtained when regressing out the effect of speech rate, and non-overlapping lesion distributions between the syndromes were confirmed by uncorrected whole brain analyses. Our results support a fundamental distinction between agrammatism and paragrammatism.

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bioRxiv2019

Neural organization of speech production: A lesion-based study of error patterns in connected speech

While numerous studies have explored single-word naming, few have evaluated the behavioral and neural correlates of more naturalistic language, like connected speech, which we produce every day. Here, in a retrospective analysis of 120 participants at least six months following left hemisphere stroke, we evaluated the distribution of word errors (paraphasias) and associated brain damage during connected speech (picture description) and object naming. While paraphasias in connected speech and naming shared underlying neural substrates, analysis of the distribution of paraphasias suggested that lexical-semantic load is likely reduced during connected speech. Using voxelwise lesion-symptom mapping (VLSM), we demonstrated that verbal (real word: semantically related and unrelated) and sound (phonemic and neologistic) paraphasias during both connected speech and naming loaded onto the left hemisphere ventral and dorsal streams of language, respectively. Furthermore, for the first time using both connected speech and naming data, we localized semantically related paraphasias to more anterior left hemisphere temporal cortex and unrelated paraphasias to more posterior left temporal and temporoparietal cortex. The connected speech results, in particular, highlight a gradient of specificity as one translates visual recognition from left temporo-occipital cortex to posterior and subsequently anterior temporal cortex. The robustness of VLSM results for sound paraphasias derived during connected speech was notable, in that analyses performed on sound paraphasias from the connected speech task, and not the naming task, demonstrated significant results following removal of lesion volume variance and related apraxia of speech variance. Therefore, connected speech may be a particularly sensitive task on which to evaluate further lexical-phonological processing in the brain. The results presented here demonstrate the related, though different, distribution of paraphasias during connected speech, confirm that paraphasias arising in connected speech and single-word naming likely share neural origins, and endorse the need for continued evaluation of the neural substrates of connected speech processes.

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bioRxiv2018

Prediction in Human Auditory Cortex

Spoken language is thought to be facilitated by an ensemble of predictive mechanisms, yet the neurobiology of prediction for both speech perception and production remains unknown. We used intracranial recordings (31 patients, 6580 electrodes) from depth probes implanted along the anteroposterior extent of the supratemporal plane during rhythm listening, speech perception, and speech production. This revealed a frequency-multiplexed encoding of sublexical features during entrainment and a traveling wave of high-frequency activity across Heschls gyrus. Critically, we isolated two predictive mechanisms in early auditory cortex with distinct anatomical and functional characteristics. The first mechanism, localized to bilateral Heschls gyrus and indexed by low-frequency phase, predicts the timing of acoustic events (\"when\"). The second mechanism, localized to planum temporale in the language-dominant hemisphere and indexed by gamma power, predicts the acoustic consequence of speech motor plans (\"what\"). This work grounds cognitive models of speech perception and production in human neurobiology, illuminating the fundamental acoustic infrastructure - both architecture and function - for spoken language.

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bioRxiv2017

The neurobiology of agrammatic sentence comprehension: a lesion study

Brocas area has long been implicated in sentence comprehension. Damage to this region is thought to be the central source of \"agrammatic comprehension\" in which performance is substantially worse (and near chance) on sentences with noncanonical word orders compared to canonical word order sentences (in English). This claim is supported by functional neuroimaging studies demonstrating greater activation in Brocas area for noncanonical versus canonical sentences. However, functional neuroimaging studies also have frequently implicated the anterior temporal lobe (ATL) in sentence processing more broadly, and recent lesion-symptom mapping studies have implicated the ATL and mid temporal regions in agrammatic comprehension. The present study investigates these seemingly conflicting findings in 66 left hemisphere patients with chronic focal cerebral damage. Patients completed two sentence comprehension measures, sentence-picture matching and plausibility judgments. Patients with damage including Brocas area (but excluding the temporal lobe; n=11) on average did not exhibit the expected agrammatic comprehension pattern, e.g. their performance was > 80% on noncanonical sentences in the sentence-picture matching task. Patients with ATL damage (n=18) also did not exhibit an agrammatic comprehension pattern. Across our entire patient sample, the lesions of patients with agrammatic comprehension patterns in either task had maximal overlap in posterior superior temporal and inferior parietal regions. Using voxel-based lesion symptom mapping (VLSM), we find that lower performances on canonical and noncanonical sentences in each task are both associated with damage to a large left superior temporal-inferior parietal network including portions of the ATL, but not Brocas area. Notably however, response bias in plausibility judgments was significantly associated with damage to inferior frontal cortex, including gray and white matter in Brocas area, suggesting that the contribution of Brocas area to sentence comprehension may be related to task-related cognitive demands.

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