Ventrolateral Frontal Region Research Articles

Association fiber tracts related to Broca's area: A comparative study based on diffusion spectrum imaging and fiber dissection.

Broca's area, made up of Brodmann areas (BA) 44 and 45 in the ventrolateral frontal region, is associated with language production and articulation. A comprehensive network analysis of Broca's area is necessary for understanding language function, which is still lacking. In this study, we attempted to investigate the association fiber tracts related to Broca's area using both diffusion spectrum imaging (DSI) and postmortem fiber dissection. DSI was performed on 10 healthy subjects and an atlas comprising the average data of 842 healthy subjects from the Human Connectome Project. Fiber dissection was implemented in 10 cerebral hemispheres of cadaver donors. The following five association fiber tracts related to Broca's area were identified: first, the distinct fasciculus of the inferior fronto-occipital fasciculus (IFOF), from Broca's area (BA44, BA45) and pars orbitalis (BA47) to the parietal and occipital lobes; second, the ventral superior longitudinal fasciculus (SLF-III), from the supramarginal gyrus (BA40) to the ventral precentral gyrus (PreG, BA6) and posterior Broca's area (BA44); third, the arcuate fascicle (AF), from the superior, middle, and inferior temporal gyrus (BA20, BA21, BA22) to Broca's area (BA44, BA45) and ventral PreG; fourth, the frontal aslant tract (FAT), from Broca's area (BA44, BA45) to the lateral superior frontal gyrus (SFG), medial SFG, and supplementary motor area (BA6, BA8, BA9); and fifth, the frontal longitudinal fasciculus (FLF), a novel intralobar frontal association fiber tract, from the anterior part of the middle frontal gyrus (MFG, BA46) and Broca's area (BA45) to the caudal MFG (BA8), caudal SFG, and dorsal PreG (BA6). Moreover, compared with the left FAT, the right FAT covered almost the entire inferior frontal gyrus (BA44, BA45, BA47). The cross validation between DSI and fiber dissection revealed a good consistence in the association fiber tracts of Broca's area. Combining DSI and fiber dissection, this study first identified five association fiber tracts related to Broca's area and characterized their structure and anatomy comprehensively. The frameworks provided key elements for functional research in Broca's area.

Frontal cortical activation during emotional and non-emotional verbal fluency tests

There has been growing recognition of the utility of combining the verbal fluency test and functional near-infrared spectroscopy (fNIRS) to assess brain functioning and to screen for psychiatric disorders. Recently, an emotional analogue of the semantic fluency test (SFT) has been developed that taps partly different processes from conventional verbal fluency tests. Nevertheless, neural processing during the emotional SFT remains elusive. Here, fNIRS was used to compare frontal cortical activation during emotional and non-emotional SFTs. The goal was to determine whether the emotional SFT activated overlapping yet distinct frontal cortical regions compared with the conventional, non-emotional SFT. Forty-three healthy young adults performed the emotional and non-emotional SFTs while hemodynamic changes in the bilateral frontopolar, dorsomedial, dorsolateral, ventrolateral, and posterolateral frontal cortices were measured by fNIRS. There were significant increases in oxyhemoglobin concentration and significant decreases in deoxyhemoglobin concentration (i.e., activation) in frontopolar, dorsolateral, and ventrolateral frontal regions during both the non-emotional and emotional SFTs. Also, complementary analyses conducted on changes in the two chromophores using classical and Bayesian hypothesis testing suggested that comparable frontal cortical regions were activated while performing the two tests. This similarity in activation occurred in a context where non-emotional and emotional SFT performances exhibited differential relationships with the overall level of negative mood symptoms. In conclusion, frontal cortical activation during the emotional SFT is similar to that during the conventional, non-emotional SFT. Given that there is evidence for discriminant validity for the emotional SFT, the neural mechanisms underlying the uniqueness of this test warrant further investigation.

Identification of the main components of spontaneous speech in primary progressive aphasia and their neural underpinnings using multimodal MRI and FDG-PET imaging

BackgroundPrimary progressive aphasia (PPA) is a clinical syndrome characterized by gradual loss of language skills. This study aimed to evaluate the diagnostic capacity of a connected speech task for the diagnosis of PPA and its variants, to determine the main components of spontaneous speech, and to examine their neural correlates. MethodsA total of 118 participants (31 patients with nfvPPA, 11 with svPPA, 45 with lvPPA, and 31 healthy controls) were evaluated with the Cookie Theft picture description task and a comprehensive language assessment protocol. Patients also underwent 18F-fluorodeoxyglucose positron emission tomography and magnetic resonance imaging studies. Principal component analysis and machine learning were used to evaluate the main components of connected speech and the accuracy of connected speech parameters for diagnosing PPA. Voxel-based analyses were conducted to evaluate the correlation between spontaneous speech components and brain metabolism, brain volumes, and white matter microstructure. ResultsDiscrimination between patients with PPA and controls was 91.67%, with 77.78% discrimination between PPA variants. Parameters related to speech rate and lexical variables were the most discriminative for classification. Three main components were identified: lexical features, fluency, and syntax. The lexical component was associated with ventrolateral frontal regions, while the fluency component was associated with the medial superior prefrontal cortex. Number of pauses was more related with the left parietotemporal region, while pauses duration with the bilateral frontal lobe. The lexical component was correlated with several tracts in the language network (left frontal aslant tract, left superior longitudinal fasciculus I, II, and III, left arcuate fasciculus, and left uncinate fasciculus), and fluency was linked to the frontal aslant tract. ConclusionSpontaneous speech assessment is a useful, brief approach for the diagnosis of PPA and its variants. Neuroimaging correlates suggested a subspecialization within the left frontal lobe, with ventrolateral regions being more associated with lexical production and the medial superior prefrontal cortex with speech rate.

Gender Differences in Aggression-related Responses on EEG and ECG.

Gender differences in aggression viewed from an evolutionary and sociocultural perspective have traditionally explained why men engage in more direct and physical aggression, and women engage in more indirect and relational aggression. However, psychological and behavioral studies offer inconsistent support for this theory due to personal or social factors, and little is known about the gender-based neurobiological mechanisms of aggression. This study investigates gender differences in aggression through an analysis of electroencephalography (EEG) and electrocardiography (ECG) based neurobiological responses to commonly encountered stimuli, as well as psychological approaches in healthy Korean youth. Our results from self-reports indicate that overall aggression indices, including physical and reactive/overt aggression, were stronger in men. This agrees with the results of previous studies. Furthermore, our study reveals prominent gender-related patterns in γ signals from the right ventrolateral frontal cortex and changes in heart rate through stimulation by aggressive videos. In particular, gender differences in EEG and ECG responses were observed in response to different scenes, as simple aversion and situation-dependent aggression, respectively. In addition, we discovered decisive gender-distinct EEG signals during stimulation of the situation-dependent aggression regions within the right ventromedial prefrontal and ventrolateral frontal regions. Our findings provide evidence of a psychological propensity for aggression and neurobiological mechanisms of oscillation underlying gender differences in aggression. Further studies of oscillatory responses to aggression and provocation will expand the objective understanding of the different emotional worlds between men and women.

Cortico-cortical connections of areas 44 and 45B in the macaque monkey

In the human brain, areas 44 and 45 constitute Broca’s region, the ventrolateral frontal region critical for language production. The homologues of these areas in the macaque monkey brain have been established by direct cytoarchitectonic comparison with the human brain. The cortical areas that project monosynaptically to areas 44 and 45B in the macaque monkey brain require clarification. Fluorescent retrograde tracers were placed in cytoarchitectonic areas 44 and 45B of the macaque monkey, as well as in the anterior part of the inferior parietal lobule and the superior temporal gyrus. The results demonstrate that ipsilateral afferent connections of area 44 arise from local frontal areas, including rostral premotor cortical area 6, from secondary somatosensory cortex, the caudal insula, and the cingulate motor region. Area 44 is strongly linked with the anterior inferior parietal lobule (particularly area PFG and the adjacent anterior intraparietal sulcus). Input from the temporal lobe is limited to the fundus of the superior temporal sulcus extending caudal to the central sulcus. There is also input from the sulcal part of area Tpt in the upper bank of the superior temporal sulcus. Area 45B shares some of the connections of area 44, but can be distinguished from area 44 by input from the caudal inferior parietal lobule (area PG) and significant input from the part of the superior temporal sulcus that extends anterior to the central sulcus. Area 45B also receives input from visual association cortex that is not observed in area 44. The results have provided a clarification of the relative connections of areas 44 and 45B of the ventrolateral frontal region which, in the human brain, subserves certain aspects of language processing.

Distinct Parietal and Temporal Connectivity Profiles of Ventrolateral Frontal Areas Involved in Language Production

Broca's region, which in the language-dominant hemisphere of the human brain plays a major role in language production, includes two distinct cytoarchitectonic areas: 44 and 45. The unique connectivity patterns of these two areas have not been well established. In a resting-state functional connectivity study, we tested predictions about these areas from invasive tract-tracing studies of the connectivity of their homologs in the macaque monkey. We demonstrated their distinct connectivity profiles as well as their differences from the caudally adjacent ventral parts of the premotor cortex and the primary motor cortical region that represent the orofacial musculature. Area 45 is strongly connected with the superior temporal sulcus and the cortex on the adjacent superior and middle temporal gyri. In the parietal region, area 45 is connected with the angular gyrus, whereas area 44 is connected with the supramarginal gyrus. The primary motor cortical region in the caudal precentral gyrus is not connected with the posterior parietal region, which lies outside the confines of the postcentral gyrus, whereas the ventrorostral premotor cortical area 6VR, in the most anterior part of the precentral gyrus, has strong connections with the rostral supramarginal gyrus. Thus, area 44, which has stronger connections to the posterior supramarginal gyrus, can be distinguished from both the adjacent area 6VR and area 45. These findings provide a major improvement in understanding the connectivity of the areas in the ventrolateral frontal region that are involved in language production.

Poster #56 CLASSIFICATION OF SCHIZOPHRENIA PATIENTS AND HEALTHY CONTROLS FROM STRUCTURAL MRI SCANS VERIFIED IN TWO LARGE INDEPENDENT SAMPLES

The frontal cortex is a heterogeneous region of the cerebral hemisphere consisting of many different cytoarchitectonic areas. The ventrolateral frontal region in the language-dominant hemisphere has been shown to be directly involved in certain aspects of language production. This frontal region includes three motor areas on the precentral gyrus (areas 4, 6VC, and 6VR) that are succeeded anteriorly by area 44 on the pars opercularis and area 45 on the pars triangularis of the inferior frontal gyrus. Areas 44 and 45 are traditionally considered to constitute Broca’s region: the anterior language production cortical zone. The posterior part of the dorsomedial frontal region, including the supplementary motor area, contributes to verbal fluency. Although damage to the various dorsolateral prefrontal cortical areas does not impair language comprehension or production, they do participate in verbal processing by virtue of their role in higher control processes that regulate attention and working memory.

Aphasia induced by gliomas growing in the ventrolateral frontal region: Assessment with diffusion MR tractography, functional MR imaging and neuropsychology

IntroductionLesions in the ventrolateral region of the dominant frontal lobe have been historically associated with aphasia. Recent imaging results suggest that frontal language regions extend beyond classically defined Broca’s area to include the ventral precentral gyrus (VPCG) and the arcuate fasciculus (AF). Frontal gliomas offer a unique opportunity to identify structures that are essential for speech production. The aim of this prospective study was to investigate the correlation between language deficits and lesion location in patients with gliomas. MethodsNineteen patients with glioma and 10 healthy subjects were evaluated with diffusion tensor imaging magnetic resonance (MR) tractography, functional MR (verb generation task) and the Aachener Aphasie Test. Patients were divided into two groups according to lesion location with respect to the ventral precentral sulcus: (i) anterior (n=8) with glioma growing in the inferior frontal gyrus (IFG) and underlying white matter; (ii) posterior (n=11) with glioma growing in the VPCG and underlying white matter. Virtual dissection of the AF, frontal intralobar tract, uncinate fasciculus (UF) and inferior frontal occipital fasciculus (IFOF) was performed with a deterministic approach. ResultsSeven posterior patients showed aphasia classified as conduction (4), Broca (1), transcortical motor (1) and an isolated deficit of semantic fluency; one anterior patient had transcortical mixed aphasia. All posterior patients had invasion of the VPCG, however only patients with aphasia had also lesion extension to the AF as demonstrated by tractography dissections. All patients with language deficits had high grade glioma. Groups did not differ regarding tumour volume. A functional pars opercularis was identified with functional MR imaging (fMRI) in 17 patients. ConclusionsGliomas growing in the left VPCG are much more likely to cause speech deficits than gliomas infiltrating the IFG, including Broca’s area. Lesion extension to the AF connecting frontal to parietal and temporal regions is an important mechanism for the appearance of aphasia.

Apathy and cortical atrophy in Alzheimer's disease

Apathy has been reported as the most prevalent behavioural symptom experienced in Alzheimer's disease (AD), associated with greater functional decline and caregiver distress. The aim of the current study was to investigate structural correlates of apathy in AD using magnetic resonance imaging (MRI) regional volume and regional cortical thickness measures. Semi-structured interviews were conducted with 111 AD patients and their caregivers as part of the European multi-centre study AddNeuroMed. Apathy was measured using the apathy domain of the Neuropsychiatric Inventory (NPI). All AD patients were scanned using a 1.5T MRI scanner and the images analysed using an automated analysis pipeline. We found apathy to be the most prevalent neuropsychiatric symptom occurring in 57% of patients. Apathetic patients had significantly greater cortical thinning in left caudal anterior cingulate cortex (ACC) and left lateral orbitofrontal cortex (OFC), as well as left superior and ventrolateral frontal regions, than those without apathy symptoms. Apathy is mediated by frontocortical structures but this is specific to the left hemisphere at least for patients in the mild to moderate stages of AD.

Neuroanatomical correlates of malingered memory impairment: Event-related fMRI of deception on a recognition memory task

Primary objective: Event-related, functional magnetic resonance imaging (fMRI) data were acquired in healthy participants during purposefully malingered and normal recognition memory performances to evaluate the neural substrates of feigned memory impairment.Methods and procedures: Pairwise, between-condition contrasts of neural activity associated with discrete recognition memory responses were conducted to isolate dissociable neural activity between normal and malingered responding while simultaneously controlling for shared stimulus familiarity and novelty effects. Response timing characteristics were also examined for any association with observed between-condition activity differences.Outcomes and results: Malingered recognition memory errors, regardless of type, were associated with inferior parietal and superior temporal activity relative to normal performance, while feigned recognition target misses produced additional dorsomedial frontal activation and feigned foil false alarms activated bilateral ventrolateral frontal regions. Malingered response times were associated with activity in the dorsomedial frontal, temporal and inferior parietal regions. Normal memory responses were associated with greater inferior occipitotemporal and dorsomedial parietal activity, suggesting greater reliance upon visual/attentional networks for proper task performance.Conclusions: The neural substrates subserving feigned recognition memory deficits are influenced by response demand and error type, producing differential activation of cortical regions important to complex visual processing, executive control, response planning and working memory processes.

Impairments of procedures for implementing complex language are due to disruption of frontal attention processes

Production of complex discourse-lengthy, open-ended utterances and narratives-requires intact basic language operations, but it also requires a series of learned procedures for construction of complex, goal-directed communications. The progression of clinical disorders from transcortical motor aphasia to dynamic aphasia to discourse impairments represents a progression of procedural deficits from basic morpho-syntax to complex grammatical structures to narrative and a progression of lesions from posterior frontal to polar and/or lateral frontal to medial frontal. Two cases of impaired utilization of language exemplify the range of impairments from clearly aphasic agrammatic, nonfluency to less and less "aphasic" and more and more executive impairments from transcortical motor aphasia to dynamic aphasia to narrative discourse disorder. The clinical phenomenology of these disorders gradually comes to be more accurately defined in the terminology of executive deficits than that of aphasia. The executive deficits are, in turn, based on impairments in various components of attention. Specific impairments in energizing attention and setting response criteria associated, respectively, with lesions in superior medial and left ventrolateral frontal regions may cause defective recruitment of the procedures of complex language assembly.

Orofacial somatomotor responses in the macaque monkey homologue of Broca's area

In the ventrolateral frontal lobe of the human brain there is a distinct entity, cytoarchitectonic area 44 (Broca's area), which is crucial in speech production. There has been controversy over whether monkeys possess an area comparable to human area 44. We have addressed this question in the macaque monkey by combining quantitative architectonic analysis of the cortical areas within the ventrolateral frontal region with electrophysiological recording of neuron activity and electrical intracortical microstimulation. Here we show that, immediately in front of the ventral part of the agranular premotor cortical area 6, there is a distinct cortical area that is architectonically comparable to human area 44 and that this monkey area 44 is involved with the orofacial musculature. We suggest that area 44 might have evolved originally as an area exercising high-level control over orofacial actions, including those related to communicative acts, and that, in the human brain, area 44 eventually also came to control certain aspects of the speech act.