Human Lateral Frontal Cortex Research Articles

Large-scale Meta-analysis Suggests Low Regional Modularity in Lateral Frontal Cortex.

Extensive fMRI study of human lateral frontal cortex (LFC) has yet to yield a consensus mapping between discrete anatomy and psychological states, partly due to the difficulty of inferring mental states from brain activity. Despite this, there have been few large-scale efforts to map the full range of psychological states across the entirety of LFC. Here, we used a data-driven approach to generate a comprehensive functional-anatomical mapping of LFC from 11 406 neuroimaging studies. We identified putatively separable LFC regions on the basis of whole-brain co-activation, revealing 14 clusters organized into 3 whole-brain networks. Next, we generated functional preference profiles by using multivariate classification to identify the psychological states that best predicted activity within each cluster. We observed large functional differences between networks, suggesting brain networks support distinct modes of processing. Within each network, however, we observed relatively low functional specificity, suggesting discrete psychological states are not strongly localized to individual regions; instead, our results are consistent with the view that individual LFC regions work as part of distributed networks to give rise to flexible behavior. Collectively, our results provide a comprehensive synthesis of a diverse neuroimaging literature using relatively unbiased data-driven methods.

Sensory-biased attention networks in human lateral frontal cortex revealed by intrinsic functional connectivity

Human frontal cortex is commonly described as being insensitive to sensory modality, however several recent studies cast doubt on this view. Our laboratory previously reported two visual-biased attention regions interleaved with two auditory-biased attention regions, bilaterally, within lateral frontal cortex. These regions selectively formed functional networks with posterior visual-biased and auditory-biased attention regions. Here, we conducted a series of functional connectivity analyses to validate and expand this analysis to 469 subjects from the Human Connectome Project (HCP). Functional connectivity analyses replicated the original findings and revealed a novel hemispheric connectivity bias. We also subdivided lateral frontal cortex into 21 thin-slice ROIs and observed bilateral patterns of spatially alternating visual-biased and auditory-biased attention network connectivity. Finally, we performed a correlation difference analysis that revealed five additional bilateral lateral frontal regions differentially connected to either the visual-biased or auditory-biased attention networks. These findings leverage the HCP dataset to demonstrate that sensory-biased attention networks may have widespread influence in lateral frontal cortical organization.

Sensory-Biased and Multiple-Demand Processing in Human Lateral Frontal Cortex.

The functionality of much of human lateral frontal cortex (LFC) has been characterized as "multiple demand" (MD) as these regions appear to support a broad range of cognitive tasks. In contrast to this domain-general account, recent evidence indicates that portions of LFC are consistently selective for sensory modality. Michalka et al. (2015) reported two bilateral regions that are biased for visual attention, superior precentral sulcus (sPCS) and inferior precentral sulcus (iPCS), interleaved with two bilateral regions that are biased for auditory attention, transverse gyrus intersecting precentral sulcus (tgPCS) and caudal inferior frontal sulcus (cIFS). In the present study, we use fMRI to examine both the multiple-demand and sensory-bias hypotheses within caudal portions of human LFC (both men and women participated). Using visual and auditory 2-back tasks, we replicate the finding of two bilateral visual-biased and two bilateral auditory-biased LFC regions, corresponding to sPCS and iPCS and to tgPCS and cIFS, and demonstrate high within-subject reliability of these regions over time and across tasks. In addition, we assess MD responsiveness using BOLD signal recruitment and multi-task activation indices. In both, we find that the two visual-biased regions, sPCS and iPCS, exhibit stronger MD responsiveness than do the auditory-biased LFC regions, tgPCS and cIFS; however, neither reaches the degree of MD responsiveness exhibited by dorsal anterior cingulate/presupplemental motor area or by anterior insula. These results reconcile two competing views of LFC by demonstrating the coexistence of sensory specialization and MD functionality, especially in visual-biased LFC structures.SIGNIFICANCE STATEMENT Lateral frontal cortex (LFC) is known to play a number of critical roles in supporting human cognition; however, the functional organization of LFC remains controversial. The "multiple demand" (MD) hypothesis suggests that LFC regions provide domain-general support for cognition. Recent evidence challenges the MD view by demonstrating that a preference for sensory modality, vision or audition, defines four discrete LFC regions. Here, the sensory-biased LFC results are reproduced using a new task, and MD responsiveness of these regions is tested. The two visual-biased regions exhibit MD behavior, whereas the auditory-biased regions have no more than weak MD responses. These findings help to reconcile two competing views of LFC functional organization.

Intrinsic functional architecture of the macaque dorsal and ventral lateral frontal cortex.

Investigations of the cellular and connectional organization of the lateral frontal cortex (LFC) of the macaque monkey provide indispensable knowledge for generating hypotheses about the human LFC. However, despite numerous investigations, there are still debates on the organization of this brain region. In vivo neuroimaging techniques such as resting-state functional magnetic resonance imaging (fMRI) can be used to define the functional circuitry of brain areas, producing results largely consistent with gold-standard invasive tract-tracing techniques and offering the opportunity for cross-species comparisons within the same modality. Our results using resting-state fMRI from macaque monkeys to uncover the intrinsic functional architecture of the LFC corroborate previous findings and inform current debates. Specifically, within the dorsal LFC, we show that 1) the region along the midline and anterior to the superior arcuate sulcus is divided in two areas separated by the posterior supraprincipal dimple, 2) the cytoarchitectonically defined area 6DC/F2 contains two connectional divisions, and 3) a distinct area occupies the cortex around the spur of the arcuate sulcus, updating what was previously proposed to be the border between dorsal and ventral motor/premotor areas. Within the ventral LFC, the derived parcellation clearly suggests the presence of distinct areas: 1) an area with a somatomotor/orofacial connectional signature (putative area 44), 2) an area with an oculomotor connectional signature (putative frontal eye fields), and 3) premotor areas possibly hosting laryngeal and arm representations. Our results illustrate in detail the intrinsic functional architecture of the macaque LFC, thus providing valuable evidence for debates on its organization.NEW & NOTEWORTHY Resting-state functional MRI is used as a complementary method to invasive techniques to inform current debates on the organization of the macaque lateral frontal cortex. Given that the macaque cortex serves as a model for the human cortex, our results help generate more fine-tuned hypothesis for the organization of the human lateral frontal cortex.

Correction: Goulas et al., Unravelling the Intrinsic Functional Organization of the Human Lateral Frontal Cortex: A Parcellation Scheme Based on Resting State fMRI

Correction: Goulas et al., Unravelling the Intrinsic Functional Organization of the Human Lateral Frontal Cortex: A Parcellation Scheme Based on Resting State fMRI

Unravelling the Intrinsic Functional Organization of the Human Lateral Frontal Cortex: A Parcellation Scheme Based on Resting State fMRI

Human and nonhuman primates exhibit flexible behavior. Functional, anatomical, and lesion studies indicate that the lateral frontal cortex (LFC) plays a pivotal role in such behavior. LFC consists of distinct subregions exhibiting distinct connectivity patterns that possibly relate to functional specializations. Inference about the border of each subregion in the human brain is performed with the aid of macroscopic landmarks and/or cytoarchitectonic parcellations extrapolated in a stereotaxic system. However, the high interindividual variability, the limited availability of cytoarchitectonic probabilistic maps, and the absence of robust functional localizers render the in vivo delineation and examination of the LFC subregions challenging. In this study, we use resting state fMRI for the in vivo parcellation of the human LFC on a subjectwise and data-driven manner. This approach succeeds in uncovering neuroanatomically realistic subregions, with potential anatomical substrates including BA 46, 44, 45, 9 and related (sub)divisions. Ventral LFC subregions exhibit different functional connectivity (FC), which can account for different contributions in the language domain, while more dorsal adjacent subregions mark a transition to visuospatial/sensorimotor networks. Dorsal LFC subregions participate in known large-scale networks obeying an external/internal information processing dichotomy. Furthermore, we traced "families" of LFC subregions organized along the dorsal-ventral and anterior-posterior axis with distinct functional networks also encompassing specialized cingulate divisions. Similarities with the connectivity of macaque candidate homologs were observed, such as the premotor affiliation of presumed BA 46. The current findings partially support dominant LFC models.

Functional organization of the left inferior precentral sulcus: Dissociating the inferior frontal eye field and the inferior frontal junction

Two eye fields have been described in the human lateral frontal cortex: the frontal eye field (FEF) and the inferior frontal eye field (iFEF). The FEF has been extensively studied and has been found to lie at the ventral part of the superior precentral sulcus. Much less research, however, has focused on the iFEF. Recently, it was suggested that the iFEF is located at the dorsal part of the inferior precentral sulcus. A similar location was proposed for the inferior frontal junction area (IFJ), an area thought to be involved in cognitive control processes. The present study used fMRI to clarify the topographical and functional relationship of the iFEF and the IFJ in the left hemispheres of individual participants. The results show that both the iFEF and the IFJ are indeed located at the dorsal part of the inferior precentral sulcus. Nevertheless, the activations were spatially dissociable in every individual examined. The IFJ was located more towards the depth of the inferior precentral sulcus, close to the junction with the inferior frontal sulcus, whereas the iFEF assumed a more lateral, posterior and superior position. Furthermore, the results provided evidence for a functional double dissociation: the iFEF was activated only in a comparison of saccades vs. button presses, but not in a comparison of incongruent vs. congruent Stroop conditions, while the opposite pattern was found at the IFJ. These results provide evidence for a spatial and functional dissociation of two directly adjacent areas in the left posterior frontal lobe.

Working memory in dorsolateral frontal cortex

It is widely held that the frontal cortex plays a critical role in certain aspects of both spatial and non-spatial working memory. The prevailing view in recent years has been that there are domain-specific subdivisions within dorsal and ventral regions of the prefrontal cortex, which subserve working memory for spatial and non-spatial information, respectively. However, Owen et al. have now used functional magnetic resonance imaging to demonstrate that performance of such tasks involves identical regions of the lateral prefrontal cortex when all factors unrelated to the type of stimulus material are appropriately controlled[1xFunctional organization of spatial and nonspatial memory processing within the human lateral frontal cortex. Owen, A.M. et al. Proc. Natl. Acad. Sci. U. S. A. 1998; 95: 7721–7726Crossref | PubMed | Scopus (263)See all References[1]. Two similar tasks, one involving the short-term retention and manipulation of spatial information and the other involving non-spatial visual patterns both activated the mid-dorsolateral frontal cortex in six subjects. These data provide evidence that spatial and non-spatial working memory might not be mediated by dorsal and ventral regions, respectively, of the frontal lobe, as widely assumed, and support the alternative notion that specific regions of the lateral frontal cortex make identical executive functional contributions to working memory.

Functional organization of spatial and nonspatial working memory processing within the human lateral frontal cortex.

The present study used functional magnetic resonance imaging to demonstrate that performance of visual spatial and visual nonspatial working memory tasks involve the same regions of the lateral prefrontal cortex when all factors unrelated to the type of stimulus material are appropriately controlled. These results provide evidence that spatial and nonspatial working memory may not be mediated, respectively, by mid-dorsolateral and mid-ventrolateral regions of the frontal lobe, as widely assumed, and support the alternative notion that specific regions of the lateral prefrontal cortex make identical executive functional contributions to both spatial and nonspatial working memory.

The functional organization of working memory processes within human lateral frontal cortex: the contribution of functional neuroimaging.

Recent functional neuroimaging studies have provided a wealth of new information about the likely organization of working memory processes within the human lateral frontal cortex. This article seeks to evaluate the results of these studies in the context of two contrasting theoretical models of lateral frontal-lobe function, developed through lesion and electrophysiological recording work in non-human primates (Goldman-Rakic, 1994, 1995; Petrides, 1994, 1995). Both models focus on a broadly similar distinction between anatomically and cytoarchitectonically distinct dorsolateral and ventrolateral frontal cortical areas, but differ in the precise functions ascribed to those regions. Following a review of the relevant anatomical data, the origins of these two theoretical positions are considered in some detail and the main predictions arising from each are identified. Recent functional neuroimaging studies of working memory processes are then critically reviewed in order to assess the extent to which they support either, or both, sets of predictions. The results of this meta-analysis suggest that lateral regions of the frontal lobe are not functionally organized according to stimulus modality, as has been widely assumed, but that specific regions within the dorsolateral or ventrolateral frontal cortex make identical functional contributions to both spatial and non-spatial working memory.

Visuo-motor conditional associative learning after frontal and temporal lesions in the human brain

It has been shown that damage to the human lateral frontal cortex results in a severe impairment on conditional associative tasks requiring learning of arbitrary associations between a set of stimuli and a set of responses (Petrides, M., Neuropsychologia, 1985, 23, 601–614; 1990, 28, 137–149). In these studies, which first demonstrated the impairment after frontal lesions, training was by a trial-and-error procedure, during which the subject performed the various responses when a given stimulus was presented and the experimenter provided feedback until the correct response was performed. In the present experiment, patients with unilateral frontal- or temporal-lobe excisions were tested on a visuo-motor conditional associative task with a modified procedure. The subjects had to learn arbitrary associations between a set of coloured stimuli and a set of hand postures. Training in the present experiment consisted of a series of demonstration trials followed by test trials. In the demonstration trials, the experimenter showed the subject the associations between the stimuli and the responses and, in the test trials that followed, the subject was tested on these associations. If an error was made on the test trials, the correct response was demonstrated by the experimenter. Despite these changes in the training procedure, namely the demonstration of the stimulus-response associations and the provision of the correct response immediately following an error, patients with left or right frontal-lobe excisions were severely impaired in learning this task. These findings, together with those of the earlier studies (Petrides, M., Neuropsychologia, 1985, 23, 601–614; 1990, 28, 137–149), demonstrate that the impairment in conditional learning after frontal lesions is not dependent on the type of the training procedure and therefore that it reflects a specific impairment in learning.

Dissociation of human mid-dorsolateral from posterior dorsolateral frontal cortex in memory processing.

Work with non-human primates had previously demonstrated that the mid-dorsolateral frontal cortex, which comprises cytoarchitectonic areas 46 and 9, plays a critical role in the performance of non-spatial self-ordered working memory tasks, whereas the immediately adjacent posterior dorsolateral frontal cortex (area 8) is critical for the learning and performance of visual conditional associative tasks. The present study used positron emission tomography with magnetic resonance imaging to demonstrate the existence, within the human brain, of these two functionally distinct subdivisions of the lateral frontal cortex. These findings provide direct evidence that, just as the monkey brain, the human lateral frontal cortex is functionally heterogeneous and that comparable anatomical areas underlie similar functions in the two species.