Broca area

Speech processing relies on the interdependence between auditory perception, sensorimotor integration, and verbal memory functions. Functional and structural connectivity between bilateral auditory-related cortical areas (ARCAs) facilitates spectro-temporal analyses, whereas the dynamic interplay between ARCAs and Broca's area (i.e., dorsal pathway) contributes to verbal memory functions, articulation, and sound-to-motor mapping. However, it remains unclear whether these two neural circuits are preferentially driven by spectral or temporal acoustic information, and whether their recruitment is predictive of speech perception performance and learning. Therefore, we evaluated EEG-based intracranial (eLORETA) functional connectivity (lagged coherence) in both pathways (i.e., between bilateral ARCAs and in the dorsal stream) while good- (GPs, N = 12) and poor performers (PPs, N = 13) learned to decode natural pseudowords (CLEAN) or comparable items (speech-noise chimeras) manipulate...

Mirror neurons, originally described in the monkey premotor area F5, are embedded in a frontoparietal network for action execution and observation. A similar Mirror Neuron System (MNS) exists in humans, including precentral gyrus, inferior parietal lobule, and superior temporal sulcus. Controversial is the inclusion of Broca's area, as homologous to F5, a relevant issue in light of the mirror hypothesis of language evolution, which postulates a key role of Broca's area in action/speech perception/production. We assess "mirror" properties of this area by combining neuroimaging and intraoperative neurophysiological techniques. Our results show that Broca's area is minimally involved in action observation and has no motor output on hand or phonoarticulatory muscles, challenging its inclusion in the MNS. The presence of these functions in premotor BA6 makes this area the likely homologue of F5 suggesting that the MNS may be involved in the representation of articulatory rather than semantic components of speech.

Combinatorial syntax has been shown to be underpinned by cortical key regions such as Broca's area and temporal cortices, and by subcortical structures such as the striatum. The cortical regions are connected via several cortico-to-cortical tracts impacting syntactic processing (e.g., the arcuate) but it remains unclear whether and how the striatum can be integrated into this cortex-centered syntax network. Here, we used a systematic stepwise approach to investigate the existence and syntactic function of an additional deep Broca-striatum pathway. We first asked 15 healthy controls and 12 patients with frontal/striatal lesions to perform three syntax tests. The results obtained were subjected to voxelbased lesion-symptom mapping (VLSM) to provide an anatomo-functional approximation of the pathway. The significant VLSM clusters were then overlapped with the probability maps of four corticocortical language tracts generated for 12 healthy participants (arcuate, extreme capsule fiber system,

Broca's area is proposed as a crucial brain area for linguistic computations. Language processing goes beyond word-level processing, also implying the integration of meaningful information (semantics) with the underlying structural skeleton (syntax). There is an on-going debate about the specialisation of the subregions of Broca's area-Brodmann areas (BA) 44 and 45-regarding the latter aspects. Here, we tested if syntactic information is specifically processed in BA 44, whereas BA 45 is mainly recruited for semantic processing. We contrasted conditions with sentence structure against conditions with random order in two fMRI experiments. Besides, in order to disentangle these processes, we systematically removed the amount of semantic information available in stimuli. This was achieved in Experiment 1 by replacing meaningful words (content words) by pseudowords. Within real words conditions we found broad activation in the left hemisphere, including the inferior frontal gyrus...

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...

Grammatical class is a fundamental property of language, and all natural languages distinguish between nouns and verbs. Brain activation studies have provided conflicting evidence concerning the neural substrates of noun and verb processing. A major limitation of many previous imaging studies is that they did not disentangle the impact of grammatical class from the differences in semantic correlates. In order to tease apart the role of semantic and grammatical factors, we performed a functional magnetic resonance imaging study presenting Italian speakers with pictures of events and asked them to name them as 1) Infinitive Verb (e.g., mangiare [to eat]); 2) Inflected Verb (e.g., mangia [she/he eats]); and 3) Action Noun (e.g., mangiata [the eating]). We did not find any verb-specific activation. However, reliable left inferior frontal gyrus (IFG) activations were found when contrasting the Action Noun with the Infinitive Verb condition. A second-level analysis indicated then that activation in left IFG was greatest for Action Nouns, intermediate for Inflected Verbs, and least for Infinitive Verbs. We conclude that, when all other factors are controlled, nouns and verbs are processed by a common neural system. In the present case, differences in left IFG activation emerge as a consequence of increasing linguistic and/or general processing demands.

Several studies have already shown that transcranial direct current stimulation (tDCS) is a useful tool for enhancing recovery in aphasia. However, no reports to date have investigated functional connectivity changes on cortical activity because of tDCS language treatment. Here, nine aphasic persons with articulatory disorders underwent an intensive language therapy in two different conditions: bilateral anodic stimulation over the left Broca's area and cathodic contralesional stimulation over the right homologue of Broca's area and a sham condition. The language treatment lasted 3 weeks (Monday to Friday, 15 daily sessions). In all patients, language measures were collected before (T0) and at the end of treatment (T15). Before and after each treatment condition (real vs. sham), each participant underwent a resting-state fMRI study. Results showed that, after real stimulation, patients exhibited the greatest recovery not only in terms of better accuracy in articulating the t...

& The aim of the present study was to determine whether Broca's area is involved in translating some aspects of arm gesture representations into mouth articulation gestures. In Experiment 1, we applied low-frequency repetitive transcranial magnetic stimulation over Broca's area and over the symmetrical loci of the right hemisphere of participants responding verbally to communicative spoken words, to gestures, or to the simultaneous presentation of the two signals. We performed also sham stimulation over the left stimulation loci. In Experiment 2, we performed the same stimulations as in Experiment 1 to participants responding with words congruent and incongruent with gestures. After sham stimulation voicing parameters were enhanced when responding to communicative spoken words or to gestures as compared to a control condition of word reading. This effect increased when participants responded to the simultaneous presentation of both communicative signals. In contrast, voicing was interfered when the verbal responses were incongruent with gestures. The left stimulation neither induced enhancement on voicing parameters of words congruent with gestures nor interference on words incongruent with gestures. We interpreted the enhancement of the verbal response to gesturing in terms of intention to interact directly. Consequently, we proposed that Broca's area is involved in the process of translating into speech aspects concerning the social intention coded by the gesture. Moreover, we discussed the results in terms of evolution to support the theory [Corballis, M. C. (2002). From hand to mouth: The origins of language. Princeton, NJ: Princeton University Press] proposing spoken language as evolved from an ancient communication system using arm gestures. &

Phonetics experts are highly trained to analyze and transcribe speech, both with respect to faster changing, phonetic features, and to more slowly changing, prosodic features. Previously we reported that, compared to nonphoneticians, phoneticians had greater local brain volume in bilateral auditory cortices and the left pars opercularis of Broca's area, with training-related differences in the greymatter volume of the left pars opercularis in the phoneticians group (Golestani et al. 2011). In the present study, we used diffusion MRI to examine white matter microstructure, indexed by fractional anisotropy, in (1) the long segment of arcuate fasciculus (AF_long), which is a wellknown language tract that connects Broca's area, including left pars opercularis, to the temporal cortex, and in (2) the fibers arising from the auditory cortices. Most of these auditory fibers belong to three validated language tracts, namely to the AF_long, the posterior segment of the arcuate fasciculus and the middle longitudinal fasciculus. We found training-related differences in phoneticians in left AF_long, as well as group differences relative to nonexperts in the auditory fibers (including the auditory fibers belonging to the left AF_long). Taken together, the results of both studies suggest that grey matter structural plasticity arising from phonetic transcription training in Broca's area is accompanied by changes to the white matter fibers connecting this very region to the temporal cortex. Our findings suggest expertise-related changes in white matter fibers connecting fronto-temporal functional hubs that are important for phonetic processing. Further studies can pursue this hypothesis by examining the dynamics of these expertise related grey and white matter changes as they arise during phonetic training.

Background: The inter-individual variability of behavioral effects after tDCS applied to the unaffected right hemisphere in stroke may be related to factors such as the lesion location. Objective/hypothesis: We investigated the effect of left Broca's area (BA) damage on picture naming in aphasic patients after cathodal tDCS applied over the right BA. Methods: We conducted a study using pre-interventional diffusion and resting state functional MRI (rsfMRI) and two cross-over tDCS sessions (TYPE: sham and cathodal) over the right homologous BA in aphasic stroke patients with ischemic lesions involving the left BA (BAþ) or other left brain areas (BAÀ). Picture naming accuracy was assessed after each session. Inter-hemispheric (IH) functional balance was investigated via rsfMRI connectivity maps using the right BA as a seed. Probabilistic tractography was used to study the integrity of language white matter pathways. Results: tDCS had different effects on picture naming accuracy in BAþ and BAÀ patients (TYPE Â GROUP interaction, F(1,19): 4.6, P: 0.04). All BAÀ patients except one did not respond to tDCS and demonstrated normal IH balance between the right and left BA when compared to healthy subjects. BAþ patients were improved by tDCS in 36% and had decreased level of functional IH balance. Improvement in picture naming after cathodal tDCS was associated with the integrity of the arcuate fasciculus in BAþ patients. Conclusions: Behavioral effects of cathodal tDCS on the unaffected right hemisphere differ depending on whether BA and the arcuate fasciculus are damaged. Therefore, IH imbalance could be a direct consequence of anatomical lesions.

The quantification of local surface morphology in the human cortex is important for examining population differences as well as developmental changes in neurodegenerative or neurodevelopmental disorders. We propose a novel cortical shape measure, referred to as the 'shape complexity index' (SCI), that represents localized shape complexity as the difference between the observed distributions of local surface topology, as quantified by the shape index (SI) measure, to its best fitting simple topological model within a given neighborhood. We apply a relatively small, adaptive geodesic kernel to calculate the SCI. Due to the small size of the kernel, the proposed SCI measure captures fine differences of cortical shape. With this novel cortical feature, we aim to capture comparatively small local surface changes that capture a) the widening versus deepening of sulcal and gyral regions, as well as b) the emergence and development of secondary and tertiary sulci. Current cortical s...

Acquisition of language skills depends on the progressive maturation of specialized brain networks that are usually lateralized in adult population. However, how genetic and environmental factors relate to the age-related differences in lateralization of these language pathways is still not known. We recruited 101 healthy right-handed subjects aged 9-40 years to investigate age-related differences in the anatomy of perisylvian language pathways and 86 adult twins (52 monozygotic and 34 dizygotic) to understand how heritability factors influence language anatomy. Diffusion tractography was used to dissect and extract indirect volume measures from the three segments of the arcuate fasciculus connecting Wernicke's to Broca's region (i.e., long segment), Broca's to Geschwind's region (i.e., anterior segment), and Wernicke's to Geschwind's region (i.e., posterior segment). We found that the long and anterior arcuate segments are lateralized before adolescence and ...

Lesion and neuroimaging studies indicate that the insula mediates motor aspects of speech production, specifically, articulatory control. Although it has direct connections to Broca's area, the canonical speech production region, the insula is also broadly connected with other speech and language centres, and may play a role in coordinating higher-order cognitive aspects of speech and language production. The extent of the insula's involvement in speech and language processing was assessed using the Activation Likelihood Estimate (ALE) method. Meta-analyses of 42 fMRI studies with healthy adults were performed, comparing insula activation during performance of language (expressive and receptive) and speech (production and perception) tasks. Both tasks activated bilateral anterior insulae. However, speech perception tasks preferentially activated the left dorsal mid-insula, whereas expressive language tasks activated left ventral mid-insula. Results suggest distinct regions of the mid-insula play different roles in speech and language processing.

To study resting cerebral blood flow in children and adults with developmental stuttering. 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. 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 an...

The primary progressive aphasias are a heterogeneous group of focal 'language-led' dementias that pose substantial challenges for diagnosis and management. Here we present a clinical approach to the progressive aphasias, based on our experience of these disorders and directed at non-specialists. We first outline a framework for assessing language, tailored to the common presentations of progressive aphasia. We then consider the defining features of the canonical progressive nonfluent, semantic and logopenic aphasic syndromes, including 'clinical pearls' that we have found diagnostically useful and neuroanatomical and other key associations of each syndrome. We review potential diagnostic pitfalls and problematic presentations not well captured by conventional classifications and propose a diagnostic 'roadmap'. After outlining principles of management, we conclude with a prospect for future progress in these diseases, emphasising generic information processing...

We investigated whether lateralized BOLD-fMRI activations in Broca's region, Wernicke's region and visual word form area (VWFA) reflect task shift costs and to which extent these effects are specific to language related task shifts. We employed a linguistic one-back memory paradigm where participants (n = 58) on each trial responded to whether a given word was the same as the previous word. In concordance with previous findings we found that conceptual shifts (CS), i.e. new words, elicited a strongly left-lateralized response in all three regions compared to repeat words. Words were sometimes presented through the visual modality (read) and sometimes through the auditory modality (spoken). This enabled the study of perceptual modality shifts (PS) relative to trials that stayed in the same modality as the previous trials. Again, we found a strongly left-lateralized effect in all regions. This was independent of whether the word was a CS or not, suggesting that linguistic translation across modalities taxes the same system as CS. Response shifts (RS), on the other hand, when shifting from one response (e.g. reporting a repeat word) to another (e.g. reporting a new word) did not yield an observable left lateralized response in any of the regions, suggesting that the lateralized task shift cost effects in these regions are not shared by all types of task shifts. Lateralization for individual tasks was found to be correlated across brain regions, but not across tasks, suggesting that lateralization may not be a unitary phenomenon, but vary across participants according to task demands. Both response time and lateralization were found to reflect the demands not only of the current trial but also of the previous trial, illustrating the context dependency of even simple cognitive tasks.

The quantification of local surface morphology in the human cortex is important for examining population differences as well as developmental changes in neurodegenerative or neurodevelopmental disorders. We propose a novel cortical shape measure, referred to as the 'shape complexity index' (SCI), that represents localized shape complexity as the difference between the observed distributions of local surface topology, as quantified by the shape index (SI) measure, to its best fitting simple topological model within a given neighborhood. We apply a relatively small, adaptive geodesic kernel to calculate the SCI. Due to the small size of the kernel, the proposed SCI measure captures fine differences of cortical shape. With this novel cortical feature, we aim to capture comparatively small local surface changes that capture a) the widening versus deepening of sulcal and gyral regions, as well as b) the emergence and development of

This paper is intended to show that a proposal (Grodzinsky & Friederici 2006) on dissociation between two types of movement (MOVE XP and MOVE V) is not supported by a critical review of data found in the literature of studies dealing with agrammatic aphasia. This procedure is considered to be of fundamental relevance for studies that plan to use evidence derived from studies based on linguistic aphasiology, since this field exhibits some problematic aspects concerning data analysis. Some conclusions reviewed here, thought to be straightforward, are, indeed, subject to questioning. In other cases, there are contradictory results that are commonly ignored in the construction of hypotheses. It is offered, then, a new posture on the consideration of the validity of studies that focus on aphasic syndromes within a linguistic framework.

Background: The inter-individual variability of behavioral effects after tDCS applied to the unaffected right hemisphere in stroke may be related to factors such as the lesion location. Objective/hypothesis: We investigated the effect of left Broca's area (BA) damage on picture naming in aphasic patients after cathodal tDCS applied over the right BA. Methods: We conducted a study using pre-interventional diffusion and resting state functional MRI (rsfMRI) and two cross-over tDCS sessions (TYPE: sham and cathodal) over the right homologous BA in aphasic stroke patients with ischemic lesions involving the left BA (BAþ) or other left brain areas (BAÀ). Picture naming accuracy was assessed after each session. Inter-hemispheric (IH) functional balance was investigated via rsfMRI connectivity maps using the right BA as a seed. Probabilistic tractography was used to study the integrity of language white matter pathways. Results: tDCS had different effects on picture naming accuracy in BAþ and BAÀ patients (TYPE Â GROUP interaction, F(1,19): 4.6, P: 0.04). All BAÀ patients except one did not respond to tDCS and demonstrated normal IH balance between the right and left BA when compared to healthy subjects. BAþ patients were improved by tDCS in 36% and had decreased level of functional IH balance. Improvement in picture naming after cathodal tDCS was associated with the integrity of the arcuate fasciculus in BAþ patients. Conclusions: Behavioral effects of cathodal tDCS on the unaffected right hemisphere differ depending on whether BA and the arcuate fasciculus are damaged. Therefore, IH imbalance could be a direct consequence of anatomical lesions.

Broca's area is crucially involved in language processing. The sub-regions of Broca's area (pars triangularis, pars opercularis) presumably are connected via corticocortical pathways. However, growing evidence suggests that the thalamus may also be involved in language and share some of the linguistic functions supported by Broca's area. Functional connectivity is thought to be achieved via corticothalamic/thalamocortical white matter pathways. Our study investigates structural connectivity between Broca's area and the thalamus, specifically ventral anterior nucleus and pulvinar. We demonstrate that Broca's area shares direct connections with these thalamic nuclei and suggest a local Broca's area-thalamus network potentially involved in linguistic processing. Thalamic connectivity with Broca's area may serve to selectively recruit cortical regions storing multimodal features of lexical items and to bind them together during lexical-semantic processing. In addition, Broca's area-thalamic circuitry may enable corticothalamo-cortical information transfer and modulation between BA 44 and 45 during language comprehension and production. Published by Elsevier Inc.

pour d epasser un certain nombre de limites rencontr ees auparavant dans l' etude de ces caract eres. Nous montrons un accroissement absolu et relatif de la taille de cette zone anatomique, a la fois pour sa largeur et sa longueur, entre Pan paniscus et Pan troglodytes, d'une part, et les hominin es, d'autre part. Par ailleurs, nous avons observ e un accroissement global de la taille de la troisi eme circonvolution frontale durant l' evolution humaine, mais des variations non-allom etriques sont aussi observ ees ind ependamment de l'augmentation du volume c er ebral au sein des diff erents echantillons d'hominin es fossiles etudi es. Enfin, nos r esultats montrent que l'asym etrie g en eralement accept ee pour l'aire de Broca est biais ee par une evaluation qualitative. La tendance au cours de l' evolution correspond a une r eduction de la taille du côt e gauche compar e au droit, mais a une meilleure d efinition de cette zone. En effet, la troisi eme circonvolution frontale est plus projet ee lat eralement et plus etendue ant ero-post erieurement a droite. En cons equence, le « cap de Broca », a gauche, est plus compact et parait plus d efini. Nos r esultats sugg erent aussi que le sch ema d'asym etrie c er ebrale est le même chez Homo sapiens et P. paniscus, laissant le gradient dans le degr e d'asym etrie comme le seul param etre structurel pertinent. Si le substrat anatomique est pr esent depuis probablement au moins l'apparence de la lign ee des hominin es, il est d es lors impossible de proposer des hypoth eses sur une eventuelle relation entre l' etendue des variations en taille, forme, asym etries de la troisi eme circonvolution frontale et l'apparition de capacit e de langage chez les hominin es.

Speech requires successful information transfer within cortical-basal ganglia loop circuits to produce the desired acoustic output. For this reason, up to 90% of Parkinson’s disease patients experience impairments of speech articulation. Deep brain stimulation (DBS) is highly effective in controlling the symptoms of Parkinson’s disease, sometimes alongside speech improvement, but subthalamic nucleus (STN) DBS can also lead to decreases in semantic and phonological fluency. This paradox demands better understanding of the interactions between the cortical speech network and the STN, which can be investigated with intracranial EEG recordings collected during DBS implantation surgery. We analyzed the propagation of high-gamma activity between STN, superior temporal gyrus (STG), and ventral sensorimotor cortices during reading aloud via event-related causality, a method that estimates strengths and directionalities of neural activity propagation. We employed a newly developed bivariate ...

Electric stimulation mapping (ESM) is frequently used during brain surgery to localise higher cognitive functions to avoid post-chirurgical disabilities. Experiments with brain imaging techniques and neuropsychological studies showed differences in the cortical representation and processing of nouns and verbs. The goal of the present study was to investigate whether electric stimulation in specific sites in the frontal cortex disrupted noun and verb production selectively. We found that most of the stimulated areas showed disruption of both verbs and nouns at the inferior frontal gyrus. However, when selective effects were obtained, verbs were more prone to disruption than nouns with important individual differences. The overall results indicate that selective impairments can be observed at inferior and middle frontal regions and the action naming task seems to be more suitable to avoid post-chirurgical language disabilities, as it shows a greater sensitivity to disruption with ESM than the classical object naming task.

Phonetics experts are highly trained to analyze and transcribe speech, both with respect to faster changing, phonetic features, and to more slowly changing, prosodic features. Previously we reported that, compared to nonphoneticians, phoneticians had greater local brain volume in bilateral auditory cortices and the left pars opercularis of Broca's area, with training-related differences in the greymatter volume of the left pars opercularis in the phoneticians group (Golestani et al. 2011). In the present study, we used diffusion MRI to examine white matter microstructure, indexed by fractional anisotropy, in (1) the long segment of arcuate fasciculus (AF_long), which is a wellknown language tract that connects Broca's area, including left pars opercularis, to the temporal cortex, and in (2) the fibers arising from the auditory cortices. Most of these auditory fibers belong to three validated language tracts, namely to the AF_long, the posterior segment of the arcuate fasciculus and the middle longitudinal fasciculus. We found training-related differences in phoneticians in left AF_long, as well as group differences relative to nonexperts in the auditory fibers (including the auditory fibers belonging to the left AF_long). Taken together, the results of both studies suggest that grey matter structural plasticity arising from phonetic transcription training in Broca's area is accompanied by changes to the white matter fibers connecting this very region to the temporal cortex. Our findings suggest expertise-related changes in white matter fibers connecting fronto-temporal functional hubs that are important for phonetic processing. Further studies can pursue this hypothesis by examining the dynamics of these expertise related grey and white matter changes as they arise during phonetic training.

Mirror neurons, originally described in the monkey premotor area F5, are embedded in a frontoparietal network for action execution and observation. A similar Mirror Neuron System (MNS) exists in humans, including precentral gyrus, inferior parietal lobule, and superior temporal sulcus. Controversial is the inclusion of Broca's area, as homologous to F5, a relevant issue in light of the mirror hypothesis of language evolution, which postulates a key role of Broca's area in action/speech perception/production. We assess "mirror" properties of this area by combining neuroimaging and intraoperative neurophysiological techniques. Our results show that Broca's area is minimally involved in action observation and has no motor output on hand or phonoarticulatory muscles, challenging its inclusion in the MNS. The presence of these functions in premotor BA6 makes this area the likely homologue of F5 suggesting that the MNS may be involved in the representation of articulatory rather than semantic components of speech.

Using conventional tDCS over the temporo-parietal junction (TPJ) we previously reported that it is possible to manipulate subjective visual vertical (SVV) and postural control. We also demonstrated that high-definition tDCS (HD-tDCS) can achieve substantially greater cortical stimulation focality than conventional tDCS. However, it is critical to establish dose-response effects using well-defined protocols with relevance to clinically meaningful applications. To conduct three pilot studies investigating polarity and intensity-dependent effects of HD-tDCS over the right TPJ on behavioral and physiological outcome measures in healthy subjects. We additionally aimed to establish the feasibility, safety, and tolerability of this stimulation protocol. We designed three separate randomized, double-blind, crossover phase I clinical trials in different cohorts of healthy adults using the same stimulation protocol. The primary outcome measure for trial 1 was SVV; trial 2, weight-bearing asym...

To assess [F]AV-1451 tau-PET uptake patterns across the primary progressive aphasia (PPA) variants (logopenic, semantic and agrammatic), examine regional uptake patterns of [F]AV-1451 independent of clinical diagnosis, and compare the diagnostic utility of [F]AV-1451, [F]-fluorodeoxygluclose (FDG)-PET and MRI to differentiate the PPA variants. We performed statistical parametric mapping of [F]AV-1451 across 40 PPA patients (logopenic-PPA=14, semantic-PPA=13 and agrammatic-PPA=13) compared to 80 cognitively normal, PiB-negative controls, age and gender matched 2:1. Principal component analysis of regional [F]AV-1451 tau-PET SUVR was performed to understand underlying patterns of [F]AV-1451 uptake independent of clinical diagnosis. Penalized multinomial regression analyses were utilized to assess diagnostic utility. Logopenic-PPA showed striking uptake throughout neocortex, particularly temporoparietal, compared to controls, semantic-PPA and agrammatic-PPA. Semantic-PPA and agrammatic...

Using conventional tDCS over the temporo-parietal junction (TPJ) we previously reported that it is possible to manipulate subjective visual vertical (SVV) and postural control. We also demonstrated that high-definition tDCS (HD-tDCS) can achieve substantially greater cortical stimulation focality than conventional tDCS. However, it is critical to establish dose-response effects using well-defined protocols with relevance to clinically meaningful applications. To conduct three pilot studies investigating polarity and intensity-dependent effects of HD-tDCS over the right TPJ on behavioral and physiological outcome measures in healthy subjects. We additionally aimed to establish the feasibility, safety, and tolerability of this stimulation protocol. We designed three separate randomized, double-blind, crossover phase I clinical trials in different cohorts of healthy adults using the same stimulation protocol. The primary outcome measure for trial 1 was SVV; trial 2, weight-bearing asym...

Acquisition of language skills depends on the progressive maturation of specialized brain networks that are usually lateralized in adult population. However, how genetic and environmental factors relate to the age-related differences in lateralization of these language pathways is still not known. We recruited 101 healthy right-handed subjects aged 9-40 years to investigate age-related differences in the anatomy of perisylvian language pathways and 86 adult twins (52 monozygotic and 34 dizygotic) to understand how heritability factors influence language anatomy. Diffusion tractography was used to dissect and extract indirect volume measures from the three segments of the arcuate fasciculus connecting Wernicke's to Broca's region (i.e., long segment), Broca's to Geschwind's region (i.e., anterior segment), and Wernicke's to Geschwind's region (i.e., posterior segment). We found that the long and anterior arcuate segments are lateralized before adolescence and ...

This review examines findings from functional neuroimaging studies of speech recognition in noise to provide a neural systems level explanation for the effort and fatigue that can be experienced during speech recognition in challenging listening conditions. Neuroimaging studies of speech recognition consistently demonstrate that challenging listening conditions engage neural systems that are used to monitor and optimize performance across a wide range of tasks. These systems appear to improve speech recognition in younger and older adults, but sustained engagement of these systems also appears to produce an experience of effort and fatigue that may affect the value of communication. When considered in the broader context of the neuroimaging and decision making literature, the speech recognition findings from functional imaging studies indicate that the expected value, or expected level of speech recognition given the difficulty of listening conditions, should be considered when measuring effort and fatigue. We propose that the behavioral economics and/or neuroeconomics of listening can provide a conceptual and experimental framework for understanding effort and fatigue that may have clinical significance.

The function of the left inferior frontal gyrus (L-IFG) is highly disputed. A number of language processing studies have linked the region to the processing of syntactical structure. Still, there is little agreement when it comes to defining why linguistic structures differ in their effects on the L-IFG. In a number of languages, the processing of object-initial sentences affects the L-IFG more than the processing of subject-initial ones, but frequency and distribution differences may act as confounding variables. Syntactically complex structures (like the object-initial construction in Danish) are often less frequent and only viable in certain contexts. With this confound in mind, the L-IFG activation may be sensitive to other variables than a syntax manipulation on its own. The present fMRI study investigates the effect of a pragmatically appropriate context on the processing of subject-initial and object-initial clauses with the IFG as our ROI. We find that Danish object-initial ...

Background: Using conventional tDCS over the temporo-parietal junction (TPJ) we previously reported that it is possible to manipulate subjective visual vertical (SVV) and postural control. We also demonstrated that high-definition tDCS (HD-tDCS) can achieve substantially greater cortical stimulation focality than conventional tDCS. However, it is critical to establish dose-response effects using well-defined protocols with relevance to clinically meaningful applications. Objective: To conduct three pilot studies investigating polarity and intensity-dependent effects of HD-tDCS over the right TPJ on behavioral and physiological outcome measures in healthy subjects. We additionally aimed to establish the feasibility, safety, and tolerability of this stimulation protocol. Methods: We designed three separate randomized, double-blind, crossover phase I clinical trials in different cohorts of healthy adults using the same stimulation protocol. The primary outcome measure for trial 1 was SVV; trial 2, weight-bearing asymmetry (WBA); and trial 3, electroencephalography power spectral density (EEG-PSD). The HD-tDCS montage comprised a single central, and 3 surround electrodes (HD-tDCS3x1) over the right TPJ. For each study, we tested 3x2 min HD-tDCS3x1 at 1, 2 and 3 mA; with anode center, cathode center, or sham stimulation, in random order across days. Results: We found significant SVV deviation relative to baseline, specific to the cathode center condition, with consistent direction and increasing with stimulation intensity. We further showed significant WBA with direction governed by stimulation polarity (cathode center, left asymmetry; anode center, right asymmetry). EEG-PSD in the gamma band was significantly increased at 3 mA under the cathode. Santos et al. Human Verticality After HD-tDCS Conclusions: The present series of studies provide converging evidence for focal neuromodulation that can modify physiology and have behavioral consequences with clinical potential.

Since the discovery of mirror neurons, there has been a great deal of interest in understanding the relationship between perception and action, and the role of the human mirror system in language comprehension and production. Two questions have dominated research. One concerns the role of Broca's area in speech perception. The other concerns the role of the motor system more broadly in understanding action-related language. The current study investigates both of these questions in a way that bridges research on language with research on manual actions. We studied the neural basis of observing and executing American Sign Language (ASL) object and action signs. In an fMRI experiment, deaf signers produced signs depicting actions and objects as well as observed/ comprehended signs of actions and objects. Different patterns of activation were found for observation and execution although with overlap in Broca's area, providing prima facie support for the claim that the motor system participates in language perception. In contrast, we found no evidence that action related signs differentially involved the motor system compared to object related signs. These findings are discussed in the context of lesion studies of sign language execution and observation. In this broader context, we conclude that the activation in Broca's area during ASL observation is not causally related to sign language understanding.

h i g h l i g h t s Magnetoencephalography (MEG) provides high localization accuracy for Broca's and Wernicke's areas. MEG reveals time latency differences between Wernicke's and Broca's areas. MEG assesses dominance in Broca's area in patients with brain tumor or epilepsy. a b s t r a c t Objective: Localizing expressive language function has been challenging using the conventional magnetoencephalography (MEG) source modeling methods. The present MEG study presents a new accurate and precise approach in localizing the language areas using a high-resolution MEG source imaging method. Methods: In 32 patients with brain tumors and/or epilepsies, an object-naming task was used to evoke MEG responses. Our Fast-VESTAL source imaging method was then applied to the MEG data in order to localize the brain areas evoked by the object-naming task. Results: The Fast-VESTAL results showed that Broca's area was accurately localized to the pars opercularis (BA 44) and/or the pars triangularis (BA 45) in all patients. Fast-VESTAL also accurately localized Wernicke's area to the posterior aspect of the superior temporal gyri in BA 22, as well as several additional brain areas. Furthermore, we found that the latency of the main peak of the response in Wernicke's area was significantly earlier than that of Broca's area. Conclusion: In all patients, Fast-VESTAL analysis established accurate and precise localizations of Broca's area, as well as other language areas. The responses in Wernicke's area were also shown to significantly precede those of Broca's area. Significance: The present study demonstrates that using Fast-VESTAL, MEG can serve as an accurate and reliable functional imaging tool for presurgical mapping of language functions in patients with brain tumors and/or epilepsies.

Background: Semantic variant primary progressive aphasia (svPPA), a clinical syndrome characterized by loss of semantic knowledge, is associated with neurodegeneration that starts in the anterior temporal lobe (ATL) and gradually spreads towards posterior temporal and medial frontal areas. At the earliest stages, atrophy may be predominantly lateralized to either the left or right ATL, leading to different clinical profiles with greatest impairment of word comprehension or visual/social semantics, respectively. Methods & Procedures: We report the in-depth longitudinal investigation of cognitive and neuroanatomical features of JB, an unusual case of ATL neurodegeneration with relative sparing of left lateral ATL regions. Outcomes & Results: Over the course of nine years, neurodegeneration progressed to involve bilateral temporo-lateral and frontal regions, resulting in a relatively symmetric and diffuse frontotemporal atrophy pattern. In parallel, JB developed greater behavioral, cognitive, and language impairments, as well as signs of motor neuron disease at her last evaluation. Episodic memory and socio-emotional processing deficits arose, likely secondary to semantic verbal deficits, while visuospatial processing, executive function, and non-semantic language abilities remained largely unaffected throughout the course of the disease. Conclusions: The details of this rare case of early medial more than lateral ATL degeneration are consistent with a bilateral organization of the semantic system and, crucially, with a functional

Significance The results of our experiments show that a special representation of sound is actually exploited by the brain during language generation, even in the absence of speech. Taking advantage of data collected during neurosurgical operations on awake patients, here we cross-correlated the cortical activity in the frontal and temporal language areas of a person reading aloud or mentally with the envelope of the sound of the corresponding utterances. In both cases, cortical activity and the envelope of the sound of the utterances were significantly correlated. This suggests that in hearing people, sound representation deeply informs generation of linguistic expressions at a much higher level than previously thought. This may help in designing new strategies to help people with language disorders such as aphasia.

Objective To further our understanding of the association between self-reported childhood learning disabilities (LDs) and atypical dementia phenotypes (Atypical Dementia), including logopenic primary progressive aphasia (L-PPA), Posterior Cortical Atrophy (PCA), and Dysexecutive-type Alzheimer's Disease (AD). Methods This retrospective case series analysis of 678 comprehensive neuropsychological assessments compared rates of self-reported LD between dementia patients diagnosed with Typical AD and those diagnosed with Atypical Dementia. 105 cases with neuroimaging or CSF data available and at least one neurology follow-up were identified as having been diagnosed by the neuropsychologist with any form of neurodegenerative dementia. These cases were subject to a consensus diagnostic process among three dementia experts using validated clinical criteria for AD and PPA. LD was considered Probable if two or more statements consistent with prior LD were documented within the Social & Developmental History of the initial neuropsychological evaluation. Results 85 subjects (Typical AD n=68, Atypical AD n=17) were included in the final analysis. In logistic regression models adjusted for age, gender, handedness, education and symptom duration, patients with Probable LD, compared to patients without Probable LD, were significantly more likely to be diagnosed with Atypical Dementia vs. Typical AD (OR 13.1, 95% CI 1.3-128.4). All three of the L-PPA cases reporting a childhood LD endorsed childhood PLOS ONE |

Temporal networks have become increasingly pervasive in many real-world applications, including the functional connectivity analysis of spatially separated regions of the brain. A major challenge in analysis of such networks is the identification of noise confounds, which introduce temporal ties that are non-essential, or links that are formed by chance due to local properties of the nodes. Several approaches have been suggested in the past for static networks or temporal networks with binary weights for extracting significant ties whose likelihood cannot be reduced to the local properties of the nodes. In this work, we propose a data-driven procedure to reveal the irreducible ties in dynamic functional connectivity of resting state fRMI data with continuous weights. This framework includes a null model that estimates the latent characteristics of the distributions of temporal links through optimization, followed by a statistical test to filter the links whose formation can be reduc...

pour d epasser un certain nombre de limites rencontr ees auparavant dans l' etude de ces caract eres. Nous montrons un accroissement absolu et relatif de la taille de cette zone anatomique, a la fois pour sa largeur et sa longueur, entre Pan paniscus et Pan troglodytes, d'une part, et les hominin es, d'autre part. Par ailleurs, nous avons observ e un accroissement global de la taille de la troisi eme circonvolution frontale durant l' evolution humaine, mais des variations non-allom etriques sont aussi observ ees ind ependamment de l'augmentation du volume c er ebral au sein des diff erents echantillons d'hominin es fossiles etudi es. Enfin, nos r esultats montrent que l'asym etrie g en eralement accept ee pour l'aire de Broca est biais ee par une evaluation qualitative. La tendance au cours de l' evolution correspond a une r eduction de la taille du côt e gauche compar e au droit, mais a une meilleure d efinition de cette zone. En effet, la troisi eme circonvolution frontale est plus projet ee lat eralement et plus etendue ant ero-post erieurement a droite. En cons equence, le « cap de Broca », a gauche, est plus compact et parait plus d efini. Nos r esultats sugg erent aussi que le sch ema d'asym etrie c er ebrale est le même chez Homo sapiens et P. paniscus, laissant le gradient dans le degr e d'asym etrie comme le seul param etre structurel pertinent. Si le substrat anatomique est pr esent depuis probablement au moins l'apparence de la lign ee des hominin es, il est d es lors impossible de proposer des hypoth eses sur une eventuelle relation entre l' etendue des variations en taille, forme, asym etries de la troisi eme circonvolution frontale et l'apparition de capacit e de langage chez les hominin es.

Acquisition of language skills depends on the progressive maturation of specialized brain networks that are usually lateralized in adult population. However, how genetic and environmental factors relate to the age-related differences in lateralization of these language pathways is still not known. We recruited 101 healthy right-handed subjects aged 9-40 years to investigate age-related differences in the anatomy of perisylvian language pathways and 86 adult twins (52 monozygotic and 34 dizygotic) to understand how heritability factors influence language anatomy. Diffusion tractography was used to dissect and extract indirect volume measures from the three segments of the arcuate fasciculus connecting Wernicke's to Broca's region (i.e., long segment), Broca's to Geschwind's region (i.e., anterior segment), and Wernicke's to Geschwind's region (i.e., posterior segment). We found that the long and anterior arcuate segments are lateralized before adolescence and ...

Background: Although pilot trials of transcranial direct current stimulation (tDCS) in aphasia are encouraging, protocol optimization is needed. Notably, it has not yet been clarified which of the varied electrode montages investigated is the most effective in enhancing language recovery. Objective: To consider and contrast the predicted brain current flow patterns (electric field distribution) produced by varied 1Â1 tDCS (1 anode, 1 cathode, 5 Â 7 cm pad electrodes) montages used in aphasia clinical trials. Methods: A finite element model of the head of a single left frontal stroke patient was developed in order to study the pattern of the cortical EF magnitude and inward/outward radial EF under five different electrode montages: Anodal-tDCS (A-tDCS) over the left Wernicke's area (Montage A) and over the left Broca's area (Montage B); Cathodal tDCS (C-tDCS) over the right homologue of Wernicke's area (Montage C), and of Broca's area (Montage D), where for all montages AD the "return" electrode was placed over the supraorbital contralateral forehead; bilateral stimulation with A-tDCS over the left Broca's and CtDCS over the right Broca's homologue (Montage E). Results: In all cases, the "return" electrode over the contralesional supraorbital forehead was not inert and influenced the current path through the entire brain. Montage B, although similar to montage D in focusing the current in the perilesional area, exerted the greatest effect over the left perilesional cortex, which was even stronger in montage E. Conclusions: The position and influence of both electrodes must be considered in the design and interpretation of tDCS clinical trials for aphasia.

Mirror neurons, originally described in the monkey premotor area F5, are embedded in a frontoparietal network for action execution and observation. A similar Mirror Neuron System (MNS) exists in humans, including precentral gyrus, inferior parietal lobule, and superior temporal sulcus. Controversial is the inclusion of Broca's area, as homologous to F5, a relevant issue in light of the mirror hypothesis of language evolution, which postulates a key role of Broca's area in action/speech perception/production. We assess "mirror" properties of this area by combining neuroimaging and intraoperative neurophysiological techniques. Our results show that Broca's area is minimally involved in action observation and has no motor output on hand or phonoarticulatory muscles, challenging its inclusion in the MNS. The presence of these functions in premotor BA6 makes this area the likely homologue of F5 suggesting that the MNS may be involved in the representation of articulatory rather than semantic components of speech.

Broca's area is proposed as a crucial brain area for linguistic computations. Language processing goes beyond word-level processing, also implying the integration of meaningful information (semantics) with the underlying structural skeleton (syntax). There is an on-going debate about the specialisation of the subregions of Broca's area-Brodmann areas (BA) 44 and 45-regarding the latter aspects. Here, we tested if syntactic information is specifically processed in BA 44, whereas BA 45 is mainly recruited for semantic processing. We contrasted conditions with sentence structure against conditions with random order in two fMRI experiments. Besides, in order to disentangle these processes, we systematically removed the amount of semantic information available in stimuli. This was achieved in Experiment 1 by replacing meaningful words (content words) by pseudowords. Within real words conditions we found broad activation in the left hemisphere, including the inferior frontal gyrus...

h i g h l i g h t s Magnetoencephalography (MEG) provides high localization accuracy for Broca's and Wernicke's areas. MEG reveals time latency differences between Wernicke's and Broca's areas. MEG assesses dominance in Broca's area in patients with brain tumor or epilepsy. a b s t r a c t Objective: Localizing expressive language function has been challenging using the conventional magnetoencephalography (MEG) source modeling methods. The present MEG study presents a new accurate and precise approach in localizing the language areas using a high-resolution MEG source imaging method. Methods: In 32 patients with brain tumors and/or epilepsies, an object-naming task was used to evoke MEG responses. Our Fast-VESTAL source imaging method was then applied to the MEG data in order to localize the brain areas evoked by the object-naming task. Results: The Fast-VESTAL results showed that Broca's area was accurately localized to the pars opercularis (BA 44) and/or the pars triangularis (BA 45) in all patients. Fast-VESTAL also accurately localized Wernicke's area to the posterior aspect of the superior temporal gyri in BA 22, as well as several additional brain areas. Furthermore, we found that the latency of the main peak of the response in Wernicke's area was significantly earlier than that of Broca's area. Conclusion: In all patients, Fast-VESTAL analysis established accurate and precise localizations of Broca's area, as well as other language areas. The responses in Wernicke's area were also shown to significantly precede those of Broca's area. Significance: The present study demonstrates that using Fast-VESTAL, MEG can serve as an accurate and reliable functional imaging tool for presurgical mapping of language functions in patients with brain tumors and/or epilepsies.