Atypical development of Broca's area in a large family with inherited stuttering.

Developmental stuttering is a condition of speech dysfluency, characterized by pauses, blocks, prolongations and sound or syllable repetitions. It affects around 1% of the population, with potential detrimental effects on mental health and long-term employment. Accumulating evidence points to a genetic aetiology, yet gene-brain associations remain poorly understood due to a lack of MRI studies in affected families. Here we report the first neuroimaging study of developmental stuttering in a family with autosomal dominant inheritance of persistent stuttering. We studied a four-generation family, 16 family members were included in genotyping analysis. T1-weighted and diffusion-weighted MRI scans were conducted on seven family members (six male; aged 9-63 years) with two age and sex matched controls without stuttering (n = 14). Using Freesurfer, we analysed cortical morphology (cortical thickness, surface area and local gyrification index) and basal ganglia volumes. White matter integrity in key speech and language tracts (i.e. frontal aslant tract and arcuate fasciculus) was also analysed using MRtrix and probabilistic tractography. We identified a significant age by group interaction effect for cortical thickness in the left hemisphere pars opercularis (Broca's area). In affected family members this region failed to follow the typical trajectory of age-related thinning observed in controls. Surface area analysis revealed the middle frontal gyrus region was reduced bilaterally in the family (all cortical morphometry significance levels set at a vertex-wise threshold of P < 0.01, corrected for multiple comparisons). Both the left and right globus pallidus were larger in the family than in the control group (left P = 0.017; right P = 0.037), and a larger right globus pallidus was associated with more severe stuttering (rho = 0.86, P = 0.01). No white matter differences were identified. Genotyping identified novel loci on chromosomes 1 and 4 that map with the stuttering phenotype. Our findings denote disruption within the cortico-basal ganglia-thalamo-cortical network. The lack of typical development of these structures reflects the anatomical basis of the abnormal inhibitory control network between Broca's area and the striatum underpinning stuttering in these individuals. This is the first evidence of a neural phenotype in a family with an autosomal dominantly inherited stuttering.

The neural basis of language development: Changes in lateralization over age.

We have long known that language is lateralized to the left hemisphere (LH) in most neurologically healthy adults. In contrast, findings on lateralization of function during development are more complex. As in adults, anatomical, electrophysiological, and neuroimaging studies in infants and children indicate LH lateralization for language. However, in very young children, lesions to either hemisphere are equally likely to result in language deficits, suggesting that language is distributed symmetrically early in life. We address this apparent contradiction by examining patterns of functional MRI (fMRI) language activation in children (ages 4 through 13) and adults (ages 18 through 29). In contrast to previous studies, we focus not on lateralization per se but rather on patterns of left-hemisphere (LH) and right-hemisphere (RH) activation across individual participants over age. Our analyses show significant activation not only in the LH language network but also in their RH homologs in all of the youngest children (ages 4 through 6). The proportion of participants showing significant RH activation decreases over age, with over 60% of adults lacking any significant RH activation. A whole-brain correlation analysis revealed an age-related decrease in language activation only in the RH homolog of Broca's area. This correlation was independent of task difficulty. We conclude that, while language is left-lateralized throughout life, the RH contribution to language processing is also strong early in life and decreases through childhood. Importantly, this early RH language activation may represent a developmental mechanism for recovery following early LH injury.

Individual Variability of Broca's Area of the Brain in Women.

In this article, we studied individual features of the macroscopic structure of Broca's area of the brains in 9 women (18 hemispheres) aged from 20 to 30 years, without any mental or neurological disorders. By using MRI, the structures of the sulci and gyri of the pars triangularis and pars opercularis of Broca's area were studied: the anterior and ascending rami of the lateral sulcus, the radial, diagonal, precentral, inferior frontal, and lateral sulci. We also studied the relationship between the pars triangularis and pars opercularis as well as their relationships with neighboring cortical structures. We measured the volume of the pars triangularis and pars opercularis and the thickness of their cortex. Significant individual variability in the location and relationships between the anterior ramus of the lateral sulcus and the ascending ramus of the lateral sulcus, as well as structural features of the pars triangularis and pars opercularis of Broca's area were demonstrated.

Functional neuroanatomy of language without speech: An ALE meta-analysis of sign language.

Sign language (SL) conveys linguistic information using gestures instead of sounds. Here, we apply a meta-analytic estimation approach to neuroimaging studies (N = 23; subjects = 316) and ask whether SL comprehension in deaf signers relies on the same primarily left-hemispheric cortical network implicated in spoken and written language (SWL) comprehension in hearing speakers. We show that: (a) SL recruits bilateral fronto-temporo-occipital regions with strong left-lateralization in the posterior inferior frontal gyrus known as Broca's area, mirroring functional asymmetries observed for SWL. (b) Within this SL network, Broca's area constitutes a hub which attributes abstract linguistic information to gestures. (c) SL-specific voxels in Broca's area are also crucially involved in SWL, as confirmed by meta-analytic connectivity modeling using an independent large-scale neuroimaging database. This strongly suggests that the human brain evolved a lateralized language network with a supramodal hub in Broca's area which computes linguistic information independent of speech.

The topographical organization of motor processing: An ALE meta-analysis on six action domains and the relevance of Broca's region.

Action is a cover term used to refer to a large set of motor processes differing in domain specificities (e.g. execution or observation). Here we review neuroimaging evidence on action processing (N = 416; Subjects = 5912) using quantitative Activation Likelihood Estimation (ALE) and Meta-Analytic Connectivity Modeling (MACM) approaches to delineate the functional specificities of six domains: (1) Action Execution, (2) Action Imitation, (3) Motor Imagery, (4) Action Observation, (5) Motor Learning, (6) Motor Preparation. Our results show distinct functional patterns for the different domains with convergence in posterior BA44 (pBA44) for execution, imitation and imagery processing. The functional connectivity network seeding in the motor-based localized cluster of pBA44 differs from the connectivity network seeding in the (language-related) anterior BA44. The two networks implement distinct cognitive functions. We propose that the motor-related network encompassing pBA44 is recruited when processing movements requiring a mental representation of the action itself.

Comparing directed functional connectivity between groups with confirmatory subgrouping GIMME.

Connectivity modeling in functional neuroimaging has become widely used method of analysis for understanding functional architecture. One method for deriving directed connectivity models is Group Iterative Multiple Model Estimation (GIMME; Gates and Molenaar, 2012). GIMME looks for commonalities across the sample to detect signal from noise and arrive at edges that exist across the majority in the group ("group-level edges") and individual-level edges. In this way, GIMME obtains generalizable results via the group-level edges while also allowing for between subject heterogeneity in connectivity, moving the field closer to obtaining reliable personalized connectivity maps. In this article, we present a novel extension of GIMME, confirmatory subgrouping GIMME, which estimates subgroup-level edges for a priori known groups (e.g. typically developing controls vs. clinical group). Detecting edges that consistently exist for individuals within predefined subgroups aids in interpretation of the heterogeneity in connectivity maps and allows for subgroup-specific inferences. We describe this algorithm, as well as several methods to examine the results. We present an empirical example that finds similarities and differences in resting state functional connectivity among four groups of children: typically developing controls (TDC), children with autism spectrum disorder (ASD), children with Inattentive (ADHD-I) and Combined (ADHD-C) Type ADHD. Findings from this study suggest common involvement of the left Broca's area in all the clinical groups, as well as several unique patterns of functional connectivity specific to a given disorder. Overall, the current approach and proof of principle findings highlight a novel and reliable tool for capturing heterogeneity in complex mental health disorders.

Universal neural basis of structure building evidenced by network modulations emerging from Broca's area: The case of Chinese.

The basic steps in building up language involve binding words of different categories into a hierarchical structure. To what extent these steps are universal or differ across languages is an open issue. Here we examine the neural dynamics of phrase structure building in Chinese-a language that in contrast to other languages heavily depends on contextual semantic information. We used functional magnetic resonance imaging and dynamic causal modeling to identify the relevant brain regions and their dynamic relations. Language stimuli consisted of syntax-driving determiners, semantics-embedded classifiers, and nonverbal symbols making up for two-component sequences manipulated by the factors structure (phrase/list) and number of words (2-word/1-word). Processing phrases compared with word lists elicited greater activation in the anterior part of Broca's area, Brodmann area (BA) 45, and the left posterior superior/middle temporal gyri (pSTG/pMTG), while processing two words against one word led to stronger involvement of the left BA 45, BA 44, and insula. Differential network modulations emerging from subparts of Broca's area revealed that phrasal construction in particular highly modulated the direct connection from BA 44 to left pMTG, suggesting BA 44's primary role in phrase structure building. Conversely, the involvement of BA 45 rather appears sensitive to the reliance on lexico-semantic information in Chinese. Against the background of previous findings from other languages, the present results indicate that phrase structure building has a universal neural basis within the left fronto-temporal network. Most importantly, they provide the first evidence demonstrating that the structure-building network may be modulated by language-specific characteristics.

Neural substrates of word category information as the basis of syntactic processing.

The ability to use word category information (WCI) for syntactic structure building has been hypothesized to be the essence of human language faculty. The neural substrate of the ability of using the WCI for the complex syntactic hierarchical structure processing, however, is yet unknown. Therefore, we directly conducted an fMRI experiment by using a pseudo-Chinese artificial language with syntactic structures containing a center-embedded relative clause. Thirty non-Chinese native (Korean) speakers were randomly divided into two groups: one acquired WCI and WCI-based syntactic rules (the WCI group) before the scanning session, and the other did not (the non-WCI group). Both groups were required to judge the grammaticality of the testing sentences, with critical long-distance dependencies between two elements (the main verb and the relativizer). Behaviorally, the WCI group's accuracy was significantly higher and its reaction time was shorter. The scanning results showed that the left superior temporal gyrus (STG) and Broca's area were more strongly activated for the WCI group, and the dynamic causal modeling analyses revealed a distinct effective connectivity pattern for this group. Therefore, the present research, for the first time, reveals that the activation of and the functional connectivity between Broca's area and the left STG play a critical role in the ability of the rule-based use of the WCI which is crucial for complex hierarchical structure building, and might be substantially corresponding to the "labeling competence" within the linguistic framework.

Larger right inferior frontal gyrus volume and surface area in participants at genetic risk for bipolar disorders.

BACKGROUND: Larger grey matter volume of the inferior frontal gyrus (IFG) is among the most replicated biomarkers of genetic risk for bipolar disorders (BD). However, the IFG is a heterogeneous prefrontal region, and volumetric findings can be attributable to changes in cortical thickness (CT), surface area (SA) or gyrification. Here, we investigated the morphometry of IFG in participants at genetic risk for BD. METHODS: We quantified the IFG cortical grey matter volume in 29 affected, 32 unaffected relatives of BD probands, and 42 controls. We then examined SA, CT, and cortical folding in subregions of the IFG. RESULTS: We found volumetric group differences in the right IFG, with the largest volumes in unaffected high-risk and smallest in control participants (F2,192 = 3.07, p = 0.01). The volume alterations were localized to the pars triangularis of the IFG (F2,97 = 4.05, p = 0.02), with no differences in pars opercularis or pars orbitalis. Pars triangularis volume was highly correlated with its SA [Pearson r(101) = 0.88, p < 0.001], which significantly differed between the groups (F2,97 = 4.45, p = 0.01). As with volume, the mean SA of the pars triangularis was greater in unaffected (corrected p = 0.02) and affected relatives (corrected p = 0.05) compared with controls. We did not find group differences in pars triangularis CT or gyrification. CONCLUSIONS: These findings strengthen prior knowledge about the volumetric findings in this region and provide a new insight into the localization and topology of IFG alterations. The unique nature of rIFG morphology in BD, with larger volume and SA early in the course of illness, could have practical implications for detection of participants at risk for BD.

Perturbation of left posterior prefrontal cortex modulates top-down processing in sentence comprehension.

Communication is an inferential process. In particular, language comprehension constantly requires top-down efforts, as often multiple interpretations are compatible with a given sentence. To assess top-down processing in the language domain, our experiment employed ambiguous sentences that allow for multiple interpretations (e.g., The client sued the murderer with the corrupt lawyer., where the corrupt lawyer could either belong to The client or the murderer). Interpretation thus depended on whether participants chunk the words of the sentence into short or long syntactic phrases. In principle, bottom-up acoustic information (i.e., the presence or absence of an intonational phrase boundary at the offset of the murderer) indicates one of the two possible interpretations. Yet, acoustic information often indicates interpretations that require words to be chunked into overly long phrases that would overburden working memory. Processing is biased against these demands, reflected in a top-down preference to chunk words into short rather than long phrases. It is often proposed, but also hotly debated, that the ability to chunk words into short phrases is subserved by the left inferior frontal gyrus (IFG). Here, we employed focal repetitive transcranial magnetic stimulation to perturb the left IFG, which resulted in a further decrease of the aptitude to tolerate long phrases, indicating the inability of the left IFG to assist the chunking of words into phrases. In contrast, the processing of auditory information was not affected. Our findings support a causal top-down role of the left inferior frontal gyrus in the chunking of words into phrases.

Transcranial direct current stimulation (tDCS) facilitates verb learning by altering effective connectivity in the healthy brain.

Recent studies have shown that the left inferior frontal gyrus (IFG) plays a key role in language learning. Facilitatory stimulation over this region by means of anodal transcranial direct current stimulation (tDCS) can modulate linguistic abilities in healthy individuals and improve language performance in patients with post-stroke aphasia. Neuroimaging studies in healthy participants have suggested that anodal tDCS decreases task-related activity at the stimulated site when applied during different language tasks, and changes resting-state connectivity in a larger network of areas associated with language processing. However, to date, the neural correlates of the potential beneficial effects of tDCS on verb learning remain unclear. The current study investigated how anodal tDCS during verb learning modulates task-related activity and effective connectivity in the healthy language network. To this end, we combined a verb learning paradigm during functional neuroimaging with simultaneous tDCS over the left IFG in healthy human volunteers. We found that, relative to sham stimulation, anodal tDCS significantly decreased task-related activity at the stimulated left IFG and in the right homologue. Effective connectivity analysis showed that anodal tDCS significantly decreased task-related functional coupling between the left IFG and the right insula. Importantly, the individual decrease in connectivity was significantly correlated with the individual behavioural improvement during anodal tDCS. These results demonstrate, for the first time, that the behavioural improvements induced by anodal tDCS might be related to an overall decrease in processing effort both with respect to task-related activity and effective connectivity within a large language network.

Tracing the interplay between syntactic and lexical features: fMRI evidence from agreement comprehension.

The current fMRI study was designed to investigate whether the processing of different gender-related cues embedded in nouns affects the computation of agreement dependencies and, if so, where this possible interaction is mapped in the brain. We used the Spanish gender agreement system, which makes it possible to manipulate two different factors: the agreement between different sentence constituents (i.e., by contrasting congruent versus incongruent determiner-noun pairs) and the formal (i.e., orthographical/morphological) and/or lexical information embedded in the noun -i.e., by contrasting transparent (e.g., libromasc. [book]; lunafem. [moon]) and opaque nouns (e.g., lápizmasc. [pencil]; vejezfem. [old age]). Crucially, these data illustrated, for the first time, how the network underlying agreement is sensitive to different gender-to-ending cues: different sources of gender information associated with nouns affect the neural circuits involved in the computation of local agreement dependencies. When the gender marking is informative (as in the case of transparent nouns), both formal and lexical information is used to establish grammatical relations. In contrast, when no formal cues are available (as in the case of opaque nouns), gender information is retrieved from the lexicon. We demonstrated the involvement of the posterior MTG/STG, pars triangularis within the IFG, and parietal regions during gender agreement computation. Critically, in order to integrate the different available information sources, the dynamics of this fronto-temporal loop change and additional regions, such as the hippocampus, the angular and the supramarginal gyri are recruited. These results underpin previous neuroanatomical models proposed in the context of both gender processing and sentence comprehension. But, more importantly, they provide valuable information regarding how and where the brain's language system dynamically integrates all the available form-based and lexical cues during comprehension.

Repeatability of language fMRI lateralization and localization metrics in brain tumor patients.

To assess the within-subject intra-scan session repeatability of language functional MRI (fMRI) activation maps in patients with brain tumors who were undergoing presurgical fMRI as part of their preoperative clinical workup. Sentence completion (SC) and silent word generation (SWG) tasks were used for language localization and hemispheric lateralization for identifying the primary language cortex. Within-subject repeatability for each of these paradigms was assessed in right-handed patients-37 for SC and 78 for SWG. Repeatability of activation maps between consecutive runs of the same task within the same scan session was evaluated by comparing lateralization indexes in holohemispheric and regional language areas. Displacement of center of activation between consecutive runs was also used to assess the repeatability of activation maps. Holohemispheric and regional language lateralization results demonstrated high intra-subject intra-scan repeatability when lateralization indices were calculated using threshold-dependent and threshold-independent approaches. The high repeatability is demonstrated both when centers of mass of activation are considered within key eloquent regions of the brain, such as Broca's area and Wernicke's area, as well as in larger more inclusive expressive and receptive language regions. We examined two well-known and widely accepted language tasks that are known to activate eloquent language cortex. We have demonstrated very high degree of repeatability at a single-subject level within single scan sessions of language mapping in a large cohort of brain tumor patients undergoing presurgical fMRI across several years at our institution.

Neural representation of word categories is distinct in the temporal lobe: An activation likelihood analysis.

The distinction between nouns and verbs is a language universal. Yet, functional neuroimaging studies comparing noun and verb processing have yielded inconsistent findings, ranging from a complete frontal(verb)-temporal(noun) dichotomy to a complete overlap in activation patterns. The current study addressed the debate about neural distinctions between nouns and verbs by conducting an activation likelihood estimation (ALE) meta-analysis of probabilistic cytoarchitectonic maps. Two levels of analysis were conducted: simple effects (Verbs vs. Baseline, Nouns vs. Baseline), and direct comparisons (Verbs vs. Nouns, Nouns vs. Verbs). Nouns were uniquely associated with a left medial temporal cluster (BA37). Activation foci for verbs included extensive inferior frontal (BA44-47) and mid-temporal (BA22, 21) regions in the left hemisphere. These findings confirm that the two grammatical classes have distinct neural architecture in supra-modal brain regions. Further, nouns and verbs overlapped in a small left lateral inferior temporal activation cluster (BA37), which is a region for modality-independent, grammatical class-independent lexical representations. These findings are most consistent with the view that as one acquires language, linguistic representations for a lexical category shift from the modality specific cortices which represent prototypical members of that category (e.g., motion for verbs) to abstract amodal representations in close proximity to modality specific cortices.

Beyond the 30-Million-Word Gap: Children's Conversational Exposure Is Associated With Language-Related Brain Function.

Children's early language exposure impacts their later linguistic skills, cognitive abilities, and academic achievement, and large disparities in language exposure are associated with family socioeconomic status (SES). However, there is little evidence about the neural mechanisms underlying the relation between language experience and linguistic and cognitive development. Here, language experience was measured from home audio recordings of 36 SES-diverse 4- to 6-year-old children. During a story-listening functional MRI task, children who had experienced more conversational turns with adults-independently of SES, IQ, and adult-child utterances alone-exhibited greater left inferior frontal (Broca's area) activation, which significantly explained the relation between children's language exposure and verbal skill. This is the first evidence directly relating children's language environments with neural language processing, specifying both an environmental and a neural mechanism underlying SES disparities in children's language skills. Furthermore, results suggest that conversational experience impacts neural language processing over and above SES or the sheer quantity of words heard.

Awake craniotomy for a cavernous angioma in the Broca's area.

Cavernous angiomas constitute 5%-10% of cerebrovascular malformations and may cause seizure and neurological deficits from bleeding. 4 The authors present a case of a 44-year-old man with a 3.5-year history of epilepsy without complete seizure control despite anticonvulsants. Brain MRI showed a 2.8 cm cavernous angioma at the left pars opercularis, also known as the Broca's area. 3 The patient underwent an awake craniotomy for intraoperative cortical-subcortical language and sensory-motor mapping for a complete resection of the cavernous angioma and the hemosiderin rim. 1-6 The procedure was uneventful, and the patient evolved seizure free and with no deficits. The video can be found here: https://youtu.be/QajbLIsr_vg .

Altered gray matter volumes in language-associated regions in children with developmental language disorder and speech sound disorder.

Developmental language disorder (DLD) and speech sound disorder (SSD) are common, and although scientific evidence for structural and functional alterations in DLD/SSD is accumulating, current neuroimaging studies provide an incongruent picture. Here, we hypothesized that children affected by DLD and SSD present with gray matter (or gray matter asymmetry) aberrations in brain areas associated with language processing compared to typically developing (TD) children. To assess this hypothesis, we enhanced MRI-based information with microscopically defined cytoarchitectonic probabilities of Broca's area (BA 45, BA 44) as well as an auditory area (TE 3.0). We detected a larger rightward gray matter asymmetry in BA 45 in children with DLD (n = 13) and with SSD (n = 18) compared to TD children (n = 18), albeit only on a trend level. Interestingly though, we observed significantly larger gray matter volumes in right BA 45 in DLD compared to SSD children (and also compared to TD children).

Reduced perfusion in Broca's area in developmental stuttering.

OBJECTIVE: To study resting cerebral blood flow in children and adults with developmental stuttering. METHODS: We acquired pulsed arterial spin labeling magnetic resonance imaging data in 26 participants with stuttering and 36 healthy, fluent controls. While covarying for age, sex, and IQ, we compared perfusion values voxel-wise across diagnostic groups and assessed correlations of perfusion with stuttering severity within the stuttering group and with measures of motor speed in both groups. RESULTS: We detected lower regional Cerebral Blood Flow (rCBF) at rest in the stuttering group compared with healthy controls in Broca's area bilaterally and the superior frontal gyrus. rCBF values in Broca's area bilaterally correlated inversely with the severity of stuttering and extended posteriorly into other portions of the language loop. We also found increased rCBF in cerebellar nuclei and parietal cortex in the stuttering group compared with healthy controls. Findings were unchanged in child-only analyses and when excluding participants with comorbid illnesses or those taking medication. CONCLUSIONS: rCBF is reduced in Broca's region in persons who stutter. More severe stuttering is associated with even greater reductions in rCBF to Broca's region, additive to the underlying putative trait reduction in rCBF relative to control values. Moreover, a greater abnormality in rCBF in the posterior language loop is associated with more severe symptoms, suggesting that a common pathophysiology throughout the language loop likely contributes to stuttering severity. Hum Brain Mapp 38:1865-1874, 2017. © 2017 Wiley Periodicals, Inc.

Sexual dimorphism of Broca's region: More gray matter in female brains in Brodmann areas 44 and 45.

Although a sexual dimorphism in brain structure is generally well established, evidence for sex differences in Brodmann areas (BA) 44 and 45 is inconclusive. This may be due to the difficulty of accurately defining BA 44 and BA 45 in magnetic resonance images, given that these regions are variable in their location and extent and that they do not match well with macroanatomic landmarks. Here we set out to test for possible sex differences in the local gray matter of BA 44/45 by integrating imaging-based signal intensities with cytoarchitectonically defined tissue probabilities in a sample of 50 male and 50 female subjects. In addition to testing for sex differences with respect to left- and right-hemispheric measures of BA 44/45, we also assessed possible sex differences in BA 44/45 asymmetry. Our analyses revealed significantly larger gray matter volumes in females compared with males for BA 44 and BA 45 bilaterally. However, there was a lack of significant sex differences in BA 44/45 asymmetry. These results corroborate reports of a language-related female superiority, particularly with respect to verbal fluency and verbal memory tasks. © 2016 Wiley Periodicals, Inc.

Brain substrates underlying auditory speech priming in healthy listeners and listeners with schizophrenia.

BACKGROUND: Under 'cocktail party' listening conditions, healthy listeners and listeners with schizophrenia can use temporally pre-presented auditory speech-priming (ASP) stimuli to improve target-speech recognition, even though listeners with schizophrenia are more vulnerable to informational speech masking. METHOD: Using functional magnetic resonance imaging, this study searched for both brain substrates underlying the unmasking effect of ASP in 16 healthy controls and 22 patients with schizophrenia, and brain substrates underlying schizophrenia-related speech-recognition deficits under speech-masking conditions. RESULTS: In both controls and patients, introducing the ASP condition (against the auditory non-speech-priming condition) not only activated the left superior temporal gyrus (STG) and left posterior middle temporal gyrus (pMTG), but also enhanced functional connectivity of the left STG/pMTG with the left caudate. It also enhanced functional connectivity of the left STG/pMTG with the left pars triangularis of the inferior frontal gyrus (TriIFG) in controls and that with the left Rolandic operculum in patients. The strength of functional connectivity between the left STG and left TriIFG was correlated with target-speech recognition under the speech-masking condition in both controls and patients, but reduced in patients. CONCLUSIONS: The left STG/pMTG and their ASP-related functional connectivity with both the left caudate and some frontal regions (the left TriIFG in healthy listeners and the left Rolandic operculum in listeners with schizophrenia) are involved in the unmasking effect of ASP, possibly through facilitating the following processes: masker-signal inhibition, target-speech encoding, and speech production. The schizophrenia-related reduction of functional connectivity between the left STG and left TriIFG augments the vulnerability of speech recognition to speech masking.