Dissecting structural connectivity of the left and right inferior frontal cortex in children who stutter.

Inferior frontal cortex pars opercularis (IFCop) features a distinct cerebral dominance and vast functional heterogeneity. Left and right IFCop are implicated in developmental stuttering. Weak left IFCop connections and divergent connectivity of hyperactive right IFCop regions have been related to impeded speech. Here, we reanalyzed diffusion magnetic resonance imaging data from 83 children (41 stuttering). We generated connection probability maps of functionally segregated area 44 parcels and calculated hemisphere-wise analyses of variance. Children who stutter showed reduced connectivity of executive, rostral-motor, and caudal-motor corticostriatal projections from the left IFCop. We discuss this finding in the context of tracing studies from the macaque area 44, which leads to the need to reconsider current models of speech motor control. Unlike the left, the right IFCop revealed increased connectivity of the inferior posterior ventral parcel and decreased connectivity of the posterior dorsal parcel with the anterior insula, particularly in stuttering boys. This divergent connectivity pattern in young children adds to the debate on potential core deficits in stuttering and challenges the theory that right hemisphere differences might exclusively indicate compensatory changes that evolve from lifelong exposure. Instead, early right prefrontal connectivity differences may reflect additional brain signatures of aberrant cognition-emotion-action influencing speech motor control.

Overlapping but Language-Specific Mechanisms in Morphosyntactic Processing in Highly Competent L2 Acquired at School Entry: fMRI Evidence From an Alternating Language Switching Task.

Many bilingual individuals acquire their second language when entering primary school; however, very few studies have investigated morphosyntax processing in this population. Combining a whole-brain and region of interest (ROI)-based approach, we studied event-related fMRI during morphosyntactic processing, specifically person-number phi-features, in Turkish (L1) and Persian (L2) by highly proficient bilinguals who learned Persian at school entry. In a design with alternating language switching and pseudorandomized grammaticality conditions, two left-lateralized syntax-specific ROIs and 11 bilateral ROIs involved in executive functions (EF) were analyzed for the intensity of activation relative to a resting baseline. Our findings indicate a strong overlap of neural networks for L1 and L2, suggesting structural similarities of neuroanatomical organization. In all ROIs morphosyntactic processing invoked stronger activation in L1 than in L2. This may be a consequence of symmetrical switch costs in the alternating design used here, where the need for suppressing the non-required language is stronger for the dominant L1 when it is non-required as compared to the non-dominant L2, leading to a stronger rebound for L1 than L2 when the language is required. Both L1 and L2 revealed significant activation in syntax-specific areas in left hemisphere clusters and increased activation in EF-specific areas in right-hemisphere than left-hemisphere clusters, confirming syntax-specific functions of the left hemisphere, whereas the right hemisphere appears to subserve control functions required for switching languages. While previous reports indicate a leftward bias in planum temporale activation during auditory and linguistic processing, the present study shows the activation of the right planum temporale indicating its involvement in auditory attention. More pronounced grammaticality effect in left pars opercularis for L1 and in left pSTG for L2 indicate differences in the processing of morphosyntactic information in these brain regions. Nevertheless, the activation of pars opercularis and pSTG emphasize the centrality of these regions in the processing of person-number phi-features. Taken together, the present results confirm that morphosyntactic processing in bilinguals relates to composite, syntax-sensitive and EF-sensitive mechanisms in which some nodes of the language network are differentially involved.

Oral and manual automatisms elicited by electrical stimulation of the pars opercularis cortex in a patient with frontal lobe epilepsy.

Oral automatism (OA) and manual automatism (MA) are common signs during initiation of temporal seizures. However, the precise symptomatogenic zones for OA and MA remains largely unclear. In this study, we presented a case of intractable frontal lobe epilepsy (FLE) in which the patient received intracranial EEG monitoring with subdural electrodes. During electrical stimulation of a grid contact located over the right pars opercularis cortex, OA and contralateral MA were observed unexpectedly without afterdischarges (ADs) or with brief ADs detected in the adjacent contacts. This case suggested that the pars opercularis cortex might play an important role in generating OA. In addition, our data implied that the symptomatogenic zone for MA might locate contralaterally to symptomatic hand.

Neuronavigated rTMS inhibition of right pars triangularis anterior in stuttering: Differential effects on reading and speaking.

Functional neuroimaging studies show an overactivation of speech and language related homologous areas of the right hemisphere in persons who stutter. In this study, we inhibited Broca's homologues using 1 Hz repetitive transcranial magnetic stimulation (rTMS) and assessed its effects on stuttering severity. The investigated cortical areas included pars opercularis (BA44), anterior and posterior pars triangularis (BA45), mouth area on the primary motor cortex (BA4). We collected reading and speaking samples before and after rTMS sessions and calculated the percentage of syllables stuttered. Only right anterior pars triangularis stimulation induced significant changes in speech fluency. Notably, the effects were differential for reading and speaking conditions. Overall, our results provide supportive evidence that right anterior BA45 may be a critical region for stuttering. The observed differential effects following the inhibition of right anterior BA45 merits further study of contributions of this region on different language domains in persons who stutter.

Task load modulates tDCS effects on language performance.

Transcranial direct current stimulation (tDCS) effects in cognition are inconsistent across studies. This study aimed to discuss why typical models might be insufficient to explain these effects, and to investigate a brain state factor, task load, with behavioral experiments on phonological processing. The motor theory of speech perception states that motor codes for articulation take part in speech perception, a view sharpened by neuroimaging findings, which show that the motor role in phonological processing is weighted by the nature of the tasks. Three groups of 20 participants, each under a different tDCS condition (anodal, cathodal, or sham), performed a categorical perception (CP), a lexical decision (LD), and a word naming (WN) task while stimulated on the pars opercularis of the left inferior frontal gyrus, a language area typically involved with the motor role. These tasks were assumed to be subserved by a network of nodes which included the target, believed to be increasingly relevant for performance from speech perception to speech production. A-tDCS facilitation and C-tDCS downregulation should directly increase with the relevance of the target for the task. Downregulation of a low relevance node could result in facilitation by compensation from other nodes. Overall, our brain stimulation findings support the neuroimaging literature in that motor participation in phonological processing depends on task nature and show that tDCS effects are modulated by task load relative to the target. Outcomes such as the improved performance following cathodal tDCS in CP and WN suggest that compensatory mechanisms may take place when the tasks involve more complex neuronal networks.

The contribution of the left inferior frontal gyrus in affective processing of social groups.

We investigated the contribution of the pars opercularis of the left inferior frontal gyrus (LIFGop) in representing knowledge about social groups. We asked healthy individuals to categorize words preceded by semantically congruent or incongruent primes while stimulating the LIFGop. Previous studies showing an involvement of the LIFGop both in processing social stimuli and negative valence words led us to predict that its stimulation would affect responses to negative social category words. Compared to the Vertex as control site, the stimulation of the LIFGop increased the speed of categorization of negative social groups, and disrupted the semantic priming effect for negative words overall. Within the framework of recent theories of semantic memory, we argue that the present results provide initial evidence of the representation of social groups being characterized by affective properties, whose processing is supported by the LIFGop.

Internet addiction associated with right pars opercularis in females.

BACKGROUND AND AIMS: Structural differences in higher-order brain areas are common features of behavioral addictions, including Internet addiction (IA) as well. Taking into consideration the limited number of studies and methods used in previous studies on IA, our aim was to investigate the correlates of IA and the morphometry of the frontal lobes. METHODS: To observe these relationships, the high-resolution T1-weighted MR images of 144 healthy, Caucasian, university students were analyzed with volumetry and voxel-based morphometry. The Problematic Internet Use Questionnaire (PIUQ) was used to assess IA. RESULTS: We found significant correlations between PIUQ subscales and the volume of the right pars opercularis volume and gray matter mass in women. DISCUSSION AND CONCLUSION: The increased gray matter measures of this structure might be explained with the extended effort to control for the impulsive behavior in addiction, and with the increased number of social interactions via the Internet.

Age sensitive associations of adolescent substance use with amygdalar, ventral striatum, and frontal volumes in young adulthood.

INTRODUCTION: This study evaluated an age sensitive model of substance use across adolescence to determine if substance use was associated with smaller volumes for an earlier developing brain region, the amygdala, a later developing region, the inferior frontal gyrus, and the ventral striatum. METHOD: Participants (N = 110) were African American young adults who were members of a longitudinal cohort across childhood and adolescence. Measures of substance use were collected across early (ages 12-15 yrs.), middle (ages 16-18 yrs.), and later (ages 19-21 yrs.) adolescence; then, at age 25, a representative subset of the sample completed magnetic resonance imaging (MRI) that assessed regional brain volumes. RESULTS: Higher levels of substance use during early adolescence, but not middle or later adolescence, were significantly associated with smaller amygdalar volume in young adulthood. Higher levels of substance use during middle adolescence, but not early or later adolescence, were significantly associated with smaller pars opercularis volume. Substance use was not associated with the pars triangularis or ventral striatum. CONCLUSION: These findings support age sensitive associations between substance use and smaller gray matter volumes at age 25 and are consistent with literature supporting the differential nature of substance use and brain maturation across adolescence and into young adulthood.

Cortical thickness of planum temporale and pars opercularis in native language tone processing.

The present study investigated the relationship between linguistic tone processing and cortical thickness of bilateral planum temporale (PT) and pars opercularis of the inferior frontal gyrus (IFGpo). Swedish tones on word stems function as cues to upcoming endings. Correlating structural brain imaging data with participants' response time patterns for suffixes, we found that thicker cortex in the left PT was associated with greater reliance on tones to anticipate upcoming inflections on real words. On inflected pseudoword stems, however, the cortical thickness of left IFGpo was associated with tone-suffix processing. Thus cortical thickness of the left PT might play a role in processing tones as part of stored representations for familiar speech segments, most likely when inflected forms are accessed as whole words. In the absence of stored representations, listeners might need to rely on morphosyntactic rules specifying tone-suffix associations, potentially facilitated by greater cortical thickness of left IFGpo.

Reviewing the functional basis of the syntactic Merge mechanism for language: A coordinate-based activation likelihood estimation meta-analysis.

The ability to create structures out of single words is a key aspect of human language. This combinatorial capacity relies on a low-level syntactic mechanism-Merge-assembling words into hierarchies. Neuroscience has explored Merge by comparing syntax to word-lists. Here, we first review potential issues with the word-lists materials. We then perform an activation likelihood estimation (ALE) on the reported foci, to reveal functional convergence for Merge at whole-brain level. Finally, we run probabilistic tractography on an independent population to observe how these convergent activations anatomically connect. Functionally, we found that when confounding activity was removed, consistency for Merge was only observable in the left pars opercularis (BA44) and in the inferior part of the posterior superior temporal sulcus/gyrus (pSTS/STG; BA22). Structurally, we could confirm that the two regions are connected through dorsal fiber bundles. We therefore suggest that the cortical implementation of linguistic Merge consists of a left fronto-temporal interaction between BA44 (syntactic processor) and pSTS/STG (integrative processor), which communicate to each other along dorsal white matter fascicles.

Graph theoretical analysis of functional network for comprehension of sign language.

Signed languages are natural human languages using the visual-motor modality. Previous neuroimaging studies based on univariate activation analysis show that a widely overlapped cortical network is recruited regardless whether the sign language is comprehended (for signers) or not (for non-signers). Here we move beyond previous studies by examining whether the functional connectivity profiles and the underlying organizational structure of the overlapped neural network may differ between signers and non-signers when watching sign language. Using graph theoretical analysis (GTA) and fMRI, we compared the large-scale functional network organization in hearing signers with non-signers during the observation of sentences in Chinese Sign Language. We found that signed sentences elicited highly similar cortical activations in the two groups of participants, with slightly larger responses within the left frontal and left temporal gyrus in signers than in non-signers. Crucially, further GTA revealed substantial group differences in the topologies of this activation network. Globally, the network engaged by signers showed higher local efficiency (t(24)=2.379, p=0.026), small-worldness (t(24)=2.604, p=0.016) and modularity (t(24)=3.513, p=0.002), and exhibited different modular structures, compared to the network engaged by non-signers. Locally, the left ventral pars opercularis served as a network hub in the signer group but not in the non-signer group. These findings suggest that, despite overlap in cortical activation, the neural substrates underlying sign language comprehension are distinguishable at the network level from those for the processing of gestural action.

Investigation of topographical anatomy of Broca's area: an anatomic cadaveric study.

PURPOSE: The sulci constituting the structure of the pars triangularis and opercularis, considered as 'Broca's area', present wide anatomical and morphological variations between different hemispheres. The boundaries are described differently from one another in various studies. The aim of this study was to explore the topographical anatomy, confirm the morphological asymmetry and highlight anatomical variations in Broca's area. METHODS: This study was performed with 100 hemispheres to investigate the presence, continuity, patterns and connections of the sulcal structures that constitute the morphological asymmetry of Broca's area. RESULTS: Considerable individual anatomical and morphological variations between the inferior frontal gyrus and related sulcal structures were detected. Rare bilateralism findings supported the morphological asymmetry. The inferior frontal sulcus was identified as a single segment in 54 % of the right and two separate segments in 52 % of the left hemispheres, which was the most common pattern. The diagonal sulcus was present in 48 % of the right and 54 % of the left hemispheres. It was most frequently connected to the ascending ramus on both sides. A 'V' shape was observed in 42.5 % of the right hemispheres and a 'Y' shape in 38.3 % of the left hemispheres, which was the most common shape of the pars triangularis. Moreover, the full results are specified in detail. CONCLUSIONS: Knowledge of the anatomical variations in this region is indispensable for understanding the functional structure and performing safe surgery. However, most previously published studies have aimed to determine the anatomical asymmetry of the motor speech area without illuminating the topographical anatomy encountered during surgery.

Preschoolers' brains rely on semantic cues prior to the mastery of syntax during sentence comprehension.

Sentence comprehension requires the integration of both syntactic and semantic information, the acquisition of which seems to have different trajectories in the developing brain. Using functional magnetic resonance imaging, we examined the neural correlates underlying syntactic and semantic processing during auditory sentence comprehension as well as its development in preschool children by manipulating case marking and animacy hierarchy cues, respectively. A functional segregation was observed within Broca's area in the left inferior frontal gyrus for adults, where the pars opercularis was involved in syntactic processing and the pars triangularis in semantic processing. By contrast, five-year-old children sensitive to animacy hierarchy cues showed diffuse activation for semantic processing in the left inferior frontal and posterior temporal cortices. While no main effect of case marking was found in the left fronto-temporal language network, children with better syntactic skills showed greater neural responses for syntactically complex sentences, most prominently in the posterior superior temporal cortex. The current study provides both behavioral and neural evidence that five-year-old children compared to adults rely more on semantic information than on syntactic cues during sentence comprehension, but with the development of syntactic abilities, their brain activation in the left fronto-temporal network increases for syntactic processing.

Merge in the Human Brain: A Sub-Region Based Functional Investigation in the Left Pars Opercularis.

Language is thought to represent one of the most complex cognitive functions in humans. Here we break down complexity of language to its most basic syntactic computation which hierarchically binds single words together to form larger phrases and sentences. So far, the neural implementation of this basic operation has only been inferred indirectly from studies investigating more complex linguistic phenomena. In the present sub-region based functional magnetic resonance imaging (fMRI) study we directly assessed the neuroanatomical nature of this process. Our results showed that syntactic phrases-compared to word-list sequences-corresponded to increased neural activity in the ventral-anterior portion of the left pars opercularis [Brodmann Area (BA) 44], whereas the adjacently located deep frontal operculum/anterior insula (FOP/aINS), a phylogenetically older and less specialized region, was found to be equally active for both conditions. Crucially, the functional activity of syntactic binding was confined to one out of five clusters proposed by a recent fine-grained sub-anatomical parcellation for BA 44, with consistency across individuals. Neuroanatomically, the present results call for a redefinition of BA 44 as a region with internal functional specializations. Neurocomputationally, they support the idea of invariance within BA 44 in the location of activation across participants for basic syntactic building processing.

Identification of the regions involved in phonological assembly using a novel paradigm.

Here we adopt a novel strategy to investigate phonological assembly. Participants performed a visual lexical decision task in English in which the letters in words and letterstrings were delivered either sequentially (promoting phonological assembly) or simultaneously (not promoting phonological assembly). A region of interest analysis confirmed that regions previously associated with phonological assembly, in studies contrasting different word types (e.g. words versus pseudowords), were also identified using our novel task that controls for a number of confounding variables. Specifically, the left pars opercularis, the superior part of the ventral precentral gyrus and the supramarginal gyrus were all recruited more during sequential delivery than simultaneous delivery, even when various psycholinguistic characteristics of the stimuli were controlled. This suggests that sequential delivery of orthographic stimuli is a useful tool to explore how readers, with various levels of proficiency, use sublexical phonological processing during visual word recognition.

Disrupting the right pars opercularis with electrical stimulation frees the song: case report.

The authors report the first case of a strikingly unusual speech impairment evoked by intraoperative electrostimulation in a 36-year-old right-handed patient, a well-trained singer, who underwent awake surgery for a right fronto-temporo-insular low-grade glioma. Functionally disrupting the pars opercularis of the right inferior frontal gyrus led the patient to automatically switch from a speaking to a singing mode of language production. Given the central role of the right pars opercularis in the inhibitory control network, the authors propose that this finding may be interpreted as possible evidence for a competitive and independent neurocognitive subnetwork devoted to the melodically intoned articulation of words (normal language-based vs singing-based) in subjects with high expertise. From a more clinical perspective, such data may have implications for awake neurosurgery, especially to preserve the quality of life for singers.

Frontal operculum gliomas: language outcome following resection.

OBJECT: The dominant hemisphere frontal operculum may contain critical speech and language pathways, and due to these properties, patients with tumors of the opercular region may be at higher risk for postoperative speech dysfunction. However, the likelihood of incurring temporary or permanent language dysfunction is unknown. METHODS: The authors retrospectively analyzed their cohort of patients with frontal gliomas to identify those tumors that predominantly involved the dominant frontal operculum. Each tumor was classified as involving the pars orbitalis, pars triangularis, pars opercularis, or a combination of some or all of these areas. The authors then identified and compared characteristics between those patients experiencing transient or permanent speech deficits, as opposed to those with no language dysfunction. RESULTS: Forty-three patients were identified for inclusion in this analysis. Transient deficits occurred in 12 patients (27.9%), while 4 patients (9.8%) had persistent deficits involving language. Individuals with preoperative language deficits and patients with seizures characterized by speech dysfunction appear to be at the highest risk to develop a deficit (relative risks 3.09 and 1.75, respectively). No patient with a tumor involving the pars orbitalis experienced a persistent deficit. CONCLUSIONS: Resection of gliomas is widely recognized as a critical element of improved outcome. Given the low rate of language morbidity reported in this group of patients, resection of gliomas within the dominant frontal operculum is well-tolerated with acceptable morbidity and, in this particular location, should not be a deterrent in the overall management of these tumors.

Early Activity in Broca's Area During Reading Reflects Fast Access to Articulatory Codes From Print.

Prior evidence for early activity in Broca's area during reading may reflect fast access to articulatory codes in left inferior frontal gyrus pars opercularis (LIFGpo). We put this hypothesis to test using a benchmark for articulatory involvement in reading known as the masked onset priming effect (MOPE). In masked onset priming, briefly presented pronounceable strings of letters that share an initial phoneme with subsequently presented target words (e.g., gilp-GAME) facilitate word naming responses compared with unrelated primes (dilp-GAME). Crucially, these priming effects only occur when the task requires articulation (naming), and not when it requires lexical decisions. A standard explanation of masked onset priming is that it reflects fast computation of articulatory output codes from letter representations. We therefore predicted 1) that activity in left IFG pars opercularis would be modulated by masked onset priming, 2) that priming-related modulation in LIFGpo would immediately follow activity in occipital cortex, and 3) that this modulation would be greater for naming than for lexical decision. These predictions were confirmed in a magnetoencephalography (MEG) priming study. MOPEs emerged in left IFG at ∼100 ms posttarget onset, and the priming effects were more sustained when the task involved articulation.

Chronic Broca's Aphasia Is Caused by Damage to Broca's and Wernicke's Areas.

Despite being perhaps the most studied form of aphasia, the critical lesion location for Broca's aphasia has long been debated, and in chronic patients, cortical damage often extends far beyond Broca's area. In a group of 70 patients, we examined brain damage associated with Broca's aphasia using voxel-wise lesion-symptom mapping (VLSM). We found that damage to the posterior portion of Broca's area, the pars opercularis, is associated with Broca's aphasia. However, several individuals with other aphasic patterns had considerable damage to pars opercularis, suggesting that involvement of this region is not sufficient to cause Broca's aphasia. When examining only individuals with pars opercularis damage, we found that patients with Broca's aphasia had greater damage in the left superior temporal gyrus (STG; roughly Wernicke's area) than those with other aphasia types. Using discriminant function analysis and logistic regression, based on proportional damage to the pars opercularis and Wernicke's area, to predict whether individuals had Broca's or another types of aphasia, over 95% were classified correctly. Our findings suggest that persons with Broca's aphasia have damage to both Broca's and Wernicke's areas, a conclusion that is incongruent with classical neuropsychology, which has rarely considered the effects of damage to both areas.

Morphometry, asymmetry and variations of the sylvian fissure and sulci bordering and within the pars triangularis and pars operculum: an autopsy study.

OBJECTIVE: Speech and Language, one of the most lateralized of all cerebral functions is located within the pars opercularis (PO) and pars triangularis (PT). There is also inter-hemispheric variability of the sulcal contours bordering these areas. The study was undertaken to note the morphometry, asymmetry and variations of the Sylvian fissure (SF), and the sulci bordering and within the PO and PT. MATERIALS AND METHODS: An adult autopsy cadaveric study was carried. The measurements made amongst others, included fronto-occipital cerebral length, cerebral width, Sylvian fissure length, and anterior Sylvian point (ASP) to inferior Rolandic point distance. The PT and PO were also studied. RESULTS: Sixty-two adult cadaveric hemispheres were studied. The SF length on the right (mean=84.3mm, median=88mm) was significantly shorter than that on the left (mean=89.4mm, median=92.0mm) (p=0.037). The anterior ascending and anterior horizontal rami of the SF arose from the ASP and either divides at this point (43 hemispheres, 69.4%) or have a common short stem before separating distally giving a Y-shape configuration. The triangularis sulcus was noted in 49 hemispheres (79%) while the diagonal sulcus was noted in 26 hemispheres (41.9%). CONCLUSION: The left SF was significantly longer than the right and both were positively correlated. The presence of the triangularis sulcus was not dependent on the side (p=0.348) or gender (0.622) unlike the diagonal sulcus was side dependent (p= 0.000).