Multimodal Association Areas Research Articles

Neuro-functional modeling of near-death experiences in contexts of altered states of consciousness.

Near-death experiences (NDEs) including out-of-body experiences (OBEs) have been fascinating phenomena of perception both for affected persons and for communities in science and medicine. Modern progress in the recording of changing brain functions during the time between clinical death and brain death opened the perspective to address and understand the generation of NDEs in brain states of altered consciousness. Changes of consciousness can experimentally be induced in well-controlled clinical or laboratory settings. Reports of the persons having experienced the changes can inform about the similarity of the experiences with those from original NDEs. Thus, we collected neuro-functional models of NDEs including OBEs with experimental backgrounds of drug consumption, epilepsy, brain stimulation, and ischemic stress, and included so far largely unappreciated data from fighter pilot tests under gravitational stress generating cephalic nervous system ischemia. Since we found a large overlap of NDE themes or topics from original NDE reports with those from neuro-functional NDE models, we can state that, collectively, the models offer scientifically appropriate causal explanations for the occurrence of NDEs. The generation of OBEs, one of the NDE themes, can be localized in the temporo-parietal junction (TPJ) of the brain, a multimodal association area. The evaluated literature suggests that NDEs may emerge as hallucination-like phenomena from a brain in altered states of consciousness (ASCs).

Eigenvector PageRank difference as a measure to reveal topological characteristics of the brain connectome for neurosurgery.

Applying graph theory to the human brain has the potential to help prognosticate the impacts of intracerebral surgery. Eigenvector (EC) and PageRank (PR) centrality are two related, but uniquely different measures of nodal centrality which may be utilized together to reveal varying neuroanatomical characteristics of the brain connectome. We obtained diffusion neuroimaging data from a healthy cohort (UCLA consortium for neuropsychiatric phenomics) and applied a personalized parcellation scheme to them. We ranked parcels based on weighted EC and PR, and then calculated the difference (EP difference) and correlation between the two metrics. We also compared the difference between the two metrics to the clustering coefficient. While EC and PR were consistent for top and bottom ranking parcels, they differed for mid-ranking parcels. Parcels with a high EC centrality but low PR tended to be in the medial temporal and temporooccipital regions, whereas PR conferred greater importance to multi-modal association areas in the frontal, parietal and insular cortices. The EP difference showed a weak correlation with clustering coefficient, though there was significant individual variation. The relationship between PageRank and eigenvector centrality can identify distinct topological characteristics of the brain connectome such as the presence of unimodal or multimodal association cortices. These results highlight how different graph theory metrics can be used alone or in combination to reveal unique neuroanatomical features for further clinical study.

Inhibition of the Deep and Intermediate Layers of the Superior Colliculus Disrupts Sensorimotor Gating in Monkeys.

The deep and intermediate layers of the superior colliculus (DLSC) respond to visual, auditory, and tactile inputs and act as a multimodal sensory association area. In turn, activity in the DLSC can drive orienting and avoidance responses—such as saccades and head and body movements—across species, including in rats, cats, and non-human primates. As shown in rodents, DLSC also plays a role in regulating pre-pulse inhibition (PPI) of the acoustic startle response (ASR), a form of sensorimotor gating. DLSC lesions attenuate PPI and electrical stimulation of DLSC inhibits the startle response. While the circuitry mediating PPI is well-characterized in rodents, less is known about PPI regulation in primates. Two recent studies from our labs reported a species difference in the effects of pharmacological inhibition of the basolateral amygdala and substantia nigra pars reticulata (SNpr) on PPI between rats and macaques: in rats, inhibition of these structures decreased PPI, while in macaques, it increased PPI. Given that the SNpr sends direct inhibitory projections to DLSC, we next sought to determine if this species difference was similarly evident at the level of DLSC. Here, we transiently inactivated DLSC in four rhesus macaques by focal microinfusion of the GABAA receptor agonist muscimol. Similar to findings reported in rodents, we observed that bilateral inhibition of the DLSC in macaques significantly disrupted PPI. The impairment was specific to the PPI as the ASR itself was not affected. These results indicate that our previously reported species divergence at the level of the SNpr is not due to downstream differences at the level of the DLSC. Species differences at the level of the SNpr and basolateral amygdala emphasize the importance of studying the underlying circuitry in non-human primates, as impairment in PPI has been reported in several disorders in humans, including schizophrenia, autism, and PTSD.

Erythrocyte omega-3 index, ambient fine particle exposure, and brain aging.

To examine whether long-chain omega-3 polyunsaturated fatty acid (LCn3PUFA) levels modify the potential neurotoxic effects of particle matter with diameters <2.5 µm (PM2.5) exposure on normal-appearing brain volumes among dementia-free elderly women. A total of 1,315 women (age 65-80 years) free of dementia were enrolled in an observational study between 1996 and 1999 and underwent structural brain MRI in 2005 to 2006. According to prospectively collected and geocoded participant addresses, we used a spatiotemporal model to estimate the 3-year average PM2.5 exposure before the MRI. We examined the joint associations of baseline LCn3PUFAs in red blood cells (RBCs) and PM2.5 exposure with brain volumes in generalized linear models. After adjustment for potential confounders, participants with higher levels of RBC LCn3PUFA had significantly greater volumes of white matter and hippocampus. For each interquartile increment (2.02%) in omega-3 index, the average volume was 5.03 cm3 (p < 0.01) greater in the white matter and 0.08 cm3 (p = 0.03) greater in the hippocampus. The associations with RBC docosahexaenoic acid and eicosapentaenoic acid levels were similar. Higher LCn3PUFA attenuated the inverse associations between PM2.5 exposure and white matter volumes in the total brain and multimodal association areas (frontal, parietal, and temporal; all p for interaction <0.05), while the associations with other brain regions were not modified. Consistent results were found for dietary intakes of LCn3PUFAs and nonfried fish. Findings from this prospective cohort study among elderly women suggest that the benefits of LCn3PUFAs on brain aging may include the protection against potential adverse effects of air pollution on white matter volumes.

Receptor-driven, multimodal mapping of cortical areas in the macaque monkey intraparietal sulcus.

The intraparietal sulcus (IPS) is structurally and functionally heterogeneous. We performed a quantitative cyto-/myelo- and receptor architectonical analysis to provide a multimodal map of the macaque IPS. We identified 17 cortical areas, including novel areas PEipe, PEipi (external and internal subdivisions of PEip), and MIPd. Multivariate analyses of receptor densities resulted in a grouping of areas based on the degree of (dis)similarity of their receptor architecture: a cluster encompassing areas located in the posterior portion of the IPS and associated mainly with the processing of visual information, a cluster including areas found in the anterior portion of the IPS and involved in sensorimotor processing, and an 'intermediate' cluster of multimodal association areas. Thus, differences in cyto-/myelo- and receptor architecture segregate the cortical ribbon within the IPS, and receptor fingerprints provide novel insights into the relationship between the structural and functional segregation of this brain region in the macaque monkey.

In vivo-assessment of the human temporal network: Evidence for asymmetrical effective connectivity

The human temporal lobe is a multimodal association area which plays a key role in various aspects of cognition, particularly in memory formation and spatial navigation. Functional and anatomical connectivity of temporal structures is thus a subject of intense research, yet by far underexplored in humans due to ethical and technical limitations. We assessed intratemporal cortico-cortical interactions in the living human brain by means of single pulse electrical stimulation, an invasive method allowing mapping effective intracortical connectivity with a high spatiotemporal resolution.Eighteen subjects with normal anterior-mesial temporal MR imaging undergoing intracranial presurgical epilepsy diagnostics with multiple depth electrodes were included. The investigated structures were temporal pole, hippocampus, amygdala and parahippocampal gyrus. Intratemporal cortical connectivity was assessed as a function of amplitude of the early component of the cortico-cortical evoked potentials (CCEP). While the analysis revealed robust interconnectivity between all explored structures, a clear asymmetry in bidirectional connectivity was detected for the hippocampal network and for the connections between the temporal pole and parahippocampal gyrus. The amygdala showed bidirectional asymmetry only to the hippocampus.The provided evidence of asymmetrically weighed intratemporal effective connectivity in humans in vivo is important for understanding of functional interactions within the temporal lobe since asymmetries in the brain connectivity define hierarchies in information processing. The findings are in exact accord with the anatomical tracing studies in non-human primates and open a translational route for interventions employing modulation of temporal lobe function.

Evolutionary expansion of connectivity between multimodal association areas in the human brain compared with chimpanzees

The development of complex cognitive functions during human evolution coincides with pronounced encephalization and expansion of white matter, the brain's infrastructure for region-to-region communication. We investigated adaptations of the human macroscale brain network by comparing human brain wiring with that of the chimpanzee, one of our closest living primate relatives. White matter connectivity networks were reconstructed using diffusion-weighted MRI in humans (n = 57) and chimpanzees (n = 20) and then analyzed using network neuroscience tools. We demonstrate higher network centrality of connections linking multimodal association areas in humans compared with chimpanzees, together with a more pronounced modular topology of the human connectome. Furthermore, connections observed in humans but not in chimpanzees particularly link multimodal areas of the temporal, lateral parietal, and inferior frontal cortices, including tracts important for language processing. Network analysis demonstrates a particularly high contribution of these connections to global network integration in the human brain. Taken together, our comparative connectome findings suggest an evolutionary shift in the human brain toward investment of neural resources in multimodal connectivity facilitating neural integration, combined with an increase in language-related connectivity supporting functional specialization.

Multiple Transmitter Receptors in Regions and Layers of the Human Cerebral Cortex

We measured the densities (fmol/mg protein) of 15 different receptors of various transmitter systems in the supragranular, granular and infragranular strata of 44 areas of visual, somatosensory, auditory and multimodal association systems of the human cerebral cortex. Receptor densities were obtained after labeling of the receptors using quantitative in vitro receptor autoradiography in human postmortem brains. The mean density of each receptor type over all cortical layers and of each of the three major strata varies between cortical regions. In a single cortical area, the multi-receptor fingerprints of its strata (i.e., polar plots, each visualizing the densities of multiple different receptor types in supragranular, granular or infragranular layers of the same cortical area) differ in shape and size indicating regional and laminar specific balances between the receptors. Furthermore, the three strata are clearly segregated into well definable clusters by their receptor fingerprints. Fingerprints of different cortical areas systematically vary between functional networks, and with the hierarchical levels within sensory systems. Primary sensory areas are clearly separated from all other cortical areas particularly by their very high muscarinic M2 and nicotinic α4β2 receptor densities, and to a lesser degree also by noradrenergic α2 and serotonergic 5-HT2 receptors. Early visual areas of the dorsal and ventral streams are segregated by their multi-receptor fingerprints. The results are discussed on the background of functional segregation, cortical hierarchies, microstructural types, and the horizontal (layers) and vertical (columns) organization in the cerebral cortex. We conclude that a cortical column is composed of segments, which can be assigned to the cortical strata. The segments differ by their patterns of multi-receptor balances, indicating different layer-specific signal processing mechanisms. Additionally, the differences between the strata-and area-specific fingerprints of the 44 areas reflect the segregation of the cerebral cortex into functionally and topographically definable groups of cortical areas (visual, auditory, somatosensory, limbic, motor), and reveals their hierarchical position (primary and unimodal (early) sensory to higher sensory and finally to multimodal association areas).Highlights Densities of transmitter receptors vary between areas of human cerebral cortex.Multi-receptor fingerprints segregate cortical layers.The densities of all examined receptor types together reach highest values in the supragranular stratum of all areas.The lowest values are found in the infragranular stratum.Multi-receptor fingerprints of entire areas and their layers segregate functional systemsCortical types (primary sensory, motor, multimodal association) differ in their receptor fingerprints.

Modality-invariant audio-visual association coding in crow endbrain neurons

Single neuron activity in the corvid nidopallium caudolaterale (NCL), the supposed avian functional analog of the prefrontal cortex, represents associations of auditory with visual stimuli. This is of high adaptive value for songbirds that need to rely on audio-visual associations to communicate, find a mate or escape predators. However, it remains unclear whether NCL neurons can represent cross-modal associations in a modality invariant, abstract fashion. To dissociate between modality-dependent and modality-invariant NCL activity, we trained two crows to match auditory sample cues with visual test stimuli, and vice versa, across a temporal memory delay. During sample presentation, NCL activity selectively encoded associations in a modality invariant fashion. During the delay, we observed subject specific, population-level coding biases in NCL activity. Despite of these biases, task relevant information could be decoded equally well from either subject’s neuronal delay activity. Decoding success was facilitated by many mixed selectivity neurons, which mediated high dimensional representations of task variables on the NCL population level. These results parallel findings from the mammalian PFC, suggesting common mechanisms responsible for the adaptability of multimodal association areas across taxa.

Dissociable changes in functional network topology underlie early category learning and development of automaticity

Recent work has shown that multimodal association areas—including frontal, temporal, and parietal cortex—are focal points of functional network reconfiguration during human learning and performance of cognitive tasks. On the other hand, neurocomputational theories of category learning suggest that the basal ganglia and related subcortical structures are focal points of functional network reconfiguration during early learning of some categorization tasks but become less so with the development of automatic categorization performance. Using a combination of network science and multilevel regression, we explore how changes in the connectivity of small brain regions can predict behavioral changes during training in a visual categorization task. We find that initial category learning, as indexed by changes in accuracy, is predicted by increasingly efficient integrative processing in subcortical areas, with higher functional specialization, more efficient integration across modules, but a lower cost in terms of redundancy of information processing. The development of automaticity, as indexed by changes in the speed of correct responses, was predicted by lower clustering (particularly in subcortical areas), higher strength (highest in cortical areas), and higher betweenness centrality. By combining neurocomputational theories and network scientific methods, these results synthesize the dissociative roles of multimodal association areas and subcortical structures in the development of automaticity during category learning.

Sharp emergence of feature-selective sustained activity along the dorsal visual pathway.

Sustained activity encoding visual working memory representations has been observed in several cortical areas of primates. Where along the visual pathways this activity emerges remains unknown. Here we show in macaques that sustained spiking activity encoding memorized visual motion directions is absent in direction-selective neurons in early visual area middle temporal (MT). However, it is robustly present immediately downstream, in multimodal association area medial superior temporal (MST), and in the lateral prefrontal cortex (LPFC). This sharp emergence of sustained activity along the dorsal pathway suggests a functional boundary between early visual areas, encoding sensory inputs, and downstream association areas, additionally encoding mnemonic representations. Moreover, local field potential oscillations in MT encoded the memorized directions and, in the low frequencies, were phase-coherent with LPFC spikes. This suggests that LPFC sustained activity modulates synaptic activity in MT, a putative top-down mechanism by which memory signals influence stimulus processing in early visual cortex.

Multimodal cortical sensory pathways revealed by sequential transcranial electrical stimulation in mice

We investigated polysynaptic cortical pathways linking primary to multimodal sensory association areas in mice using transcranial flavoprotein imaging combined with sequential application of transcranial electrical stimulation (TES). Stimulation of primary visual cortex (V1) elicited activity in lateral and medial areas of secondary visual cortices (V2), which were reciprocally connected. Stimulation of V2 areas elicited activity in area 2. Similarly, corticocortical pathways from primary somatosensory cortex (S1) through the corresponding secondary somatosensory areas (S2) to area 2 were observed. Auditory pathways from primary auditory area (A1) through peripheral region (area 22) to area 2 and from anterior auditory field to area 2 were also found. Stimulation in area 2 elicited activity in part of parietal association cortex (PtA), which was reciprocally connected with area 2, and in some areas near the midline including retrosplenial cortex (RSA). A cortical pathway from RSA through anterior cingulate cortex (aCC) to frontal areas was also visualized. These results indicate that area 2, surrounded by visual, somatosensory and auditory cortices, may receive inputs from all three primary sensory areas, and may send outputs through the parietal association cortex to frontal areas, suggesting that area 2 may have an important role in multimodal sensory integration in mice.

Is a single ‘hub’, with lots of spokes, an accurate description of the neural architecture of action semantics?: Comment on “Action semantics: A unifying conceptual framework for the selective use of multimodal and modality-specific object knowledge” by van Elk, van Schie and Bekkering

How is knowledge about tools and their associated actions represented in the brain? In their otherwise excellentreview of the behavioral, developmental, and neuropsychological literatures, Van Elk, van Schie, and Bekkering [16]argue that the so-called ‘hub and spoke’ architecture [12] provides a good answer. Semantics, in this model, is “rep-resented across modality-specific ‘spokes’ that converge in a multimodal association area (i.e. the ‘semantic hub’)that provides an amodal representation of semantic information”. Exactly what type of information is contained inan ‘amodal’ object representation, and how this representation is created from the convergence of information frommultiple modalities, is left unsaid.Leaving aside these thorny theory-laden concerns, in this comment we highlight several problems with the ‘huband spoke’ architecture. The semantic ‘hub’ is claimed to reside in a specific region of the brain, the anterior temporallobes, bilaterally (ATL). This claim is largely based on the notion that the clinical disorder of semantic dementia iscaused solely by damage limited to the ATL. This is not the case. Semantic dementia is a progressive disorder thattypically involves a broad expanse of temporal, and often frontal, cortex, as well as subcortical regions – especiallyduring the later stages when conceptual knowledge is most degraded (e.g., [5]). More to the point, even if the dam-age associated with semantic dementia was limited to the ATL, the fact that this damage produces semantic deficitsinvolving multiple object categories and concepts does not constitute evidence for a semantic ‘hub’ any more so thanwould finding that damage to posterior temporal cortex – a brain region known to represent multiple object categoriesin spatially distinct regions – constitute evidence for an object perception ‘hub’.

Receptor architecture of visual areas in the face and word-form recognition region of the posterior fusiform gyrus

Recently, two extrastriate visual areas on the posterior fusiform gyrus, areas FG1 and FG2, were identified based on cytoarchitectonical criteria (Caspers et al. in Brain Struct Funct 218:511-526, 2013a). They are located within the object-related ventral visual stream at the transition between early and higher-order (category-specific) visual areas. FG2 has a topographical position which is best comparable to the face or visual word-form recognition area. However, the precise function of FG2 is presently unknown. Since transmitter receptors are key molecules of neurotransmission, we analysed the regional and laminar distribution of 15 different receptor binding sites by means of quantitative in vitro receptor autoradiography. Significant differences between receptor densities of both areas were found for NMDA, GABAB, M3, nicotinic α4/β2 and 5-HT1A receptors as well as for GABAA associated benzodiazepine binding sites. These results support the cytoarchitectonic segregation of FG1 and FG2 into two distinct cortical areas. In addition, principal component and hierarchical cluster analyses of the multireceptor data of both fusiform areas and 24 visual, auditory, somatosensory and multimodal association areas not only revealed the typical receptor architectonic characteristics of visual areas for FG1 and FG2, but also suggest their putative function as object recognition regions due to the similarity of their receptor fingerprints with those of areas of the ventral visual stream. Furthermore, FG1 and FG2 build a cluster with the multimodal association areas of the inferior parietal lobule. This underlines their hierarchically high position in the visual system of the human cerebral cortex.

Episodic-like memory and divergent brain systems in mammals and birds

In their review in PNAS, Allen and Fortin use a comparative neuroanatomical approach to gain insight into the evolution of episodic memory (1). The authors suggest that, as in humans, episodic-like memory in nonhuman mammals depends on a system consisting of the hippocampus, parahippocampal region, and prefrontal cortex (PFC), and, in birds, a similar system consisting of the hippocampus, area parahippocampalis, and nidopallium caudolaterale (NCL), the avian analog of the PFC. Although we agree that the behavioral evidence for episodic-like memory in birds is compelling, in contrast to Allen and Fortin, our interpretation of the available neuroanatomical evidence indicates that key components of this system are missing in birds. In mammals, the PFC is thought to assess the relevance of episodic memories recalled from the hippocampus via its connections with the hippocampus, parahippocampal region, and other higher association areas reactivated during recall and to, then, orchestrate behavior accordingly through projections to motor areas (1). Like the PFC, the NCL is reciprocally connected to higher association and motor output regions and appears to perform executive functions (2). However, of the laboratories (at least four) that have addressed this question, none has detected connections between the NCL and the area parahippocampalis or hippocampus (3) (reviewed in ref. 4). This may be related to the fact that the PFC and NCL are analogous structures that evolved independently and develop from different parts of the pallium; in mammals, the PFC develops from the dorsal pallium, whereas in birds the NCL and the rest of the dorsal ventricular ridge (DVR) develop from the lateral and ventral pallium (5). Interestingly, in birds, rather than developing into a higher-order multimodal association area, such as the PFC, the dorsal pallium develops into the hyperpallium, a structure composed of primary visual and somatosensory/motor subregions (5). Nonetheless, consistent with its developmental homology with mammalian dorsal pallial derivatives, the hyperpallium shares PFC-like connections to the hippocampus, area parahippocampalis, and motor output regions (5) and, as suggested by Bingman and coworkers, may bridge the apparent gap between the hippocampus and NCL by conveying spatial (visual and olfactory) information via known projections to the NCL (3). The NCL could then integrate this information with that received from other association regions in the DVR and, thereby, orchestrate adaptive behaviors. Although this pathway may provide a route for integrating information processed by the hippocampus, hyperpallium, and DVR, additional differences exist between birds and mammals that likely influence the nature of episodic-like memory in the two groups. Unlike mammals, wherein highly processed information from virtually the entire neocortex converges in the hippocampus, enabling it to serve as a node for rapidly encoding experiences and initiating their recall, the avian hippocampus only receives olfactory and visual input and is not privy to much of the information processed by association regions in the DVR (nidopallium and mesopallium), in addition to the NCL (4). Given these fundamental differences in neuroanatomy, to the extent that episodic-like memory depends on information reaching the hippocampus, such memories may be qualitatively different between birds and mammals.

Analysis of abstract and concrete word processing in persons with aphasia and age-matched neurologically healthy adults using fMRI

The concreteness effect occurs in both normal and language-disordered populations. Research suggests that abstract and concrete concepts elicit differing neural activation patterns in healthy young adults, but this is undocumented in persons with aphasia (PWA). Three PWA and three age-matched controls were scanned using fMRI while processing abstract and concrete words. Consistent with current theories of abstract and concrete word processing, abstract words elicited activation in verbal areas, whereas concrete words additionally activated multimodal association areas. PWA show greater differences in neural activation than age-matched controls between abstract and concrete words, possibly due to an exaggerated concreteness effect.

A Self-Organized Artificial Neural Network Architecture for Sensory Integration with Applications to Letter-Phoneme Integration

The multimodal self-organizing network (MMSON), an artificial neural network architecture carrying out sensory integration, is presented here. The architecture is designed using neurophysiological findings and imaging studies that pertain to sensory integration and consists of interconnected lattices of artificial neurons. In this artificial neural architecture, the degree of recognition of stimuli, that is, the perceived reliability of stimuli in the various subnetworks, is included in the computation. The MMSON's behavior is compared to aspects of brain function that deal with sensory integration. According to human behavioral studies, integration of signals from sensory receptors of different modalities enhances perception of objects and events and also reduces time to detection. In neocortex, integration takes place in bimodal and multimodal association areas and result, not only in feedback-mediated enhanced unimodal perception and shortened reaction time, but also in robust bimodal or multimodal percepts. Simulation data from the presented artificial neural network architecture show that it replicates these important psychological and neuroscientific characteristics of sensory integration.

Insula, a “mysterious” island in our brain – minireview

Until the last decade of the past century, insula was one of the less frequently investigated cortical areas in the human brain. Due to the introduction and wide use of neuroimaging techniques in human brain, insula became the focus of attention. Recent studies confirmed former observations about the presence of the olfactory, taste and viscerosensory cortical centers in the insula, and provided very fine new information about the mechanism of actions and interactions of these activities. Furthermore, the functional significance of insula in social-emotional, cognitive and sensorimotor network, speech and language processes, as well as in interoceptive awareness have been determined. For performing of these activities, insula receives extensive neuronal input from the body and from various cortical areas. Through its opercular cortices and the anterior cingulate cortex, insula is connected to prefrontal, premotor, limbic and central autonomic areas. With our present knowledge, insula may serve as primary (unimodal) cortical area for olfactory, taste and viscerosensory information, and acts as a multimodal cortical association area in the emotional, cognitive, limbic and autonomic systems in the brain.

The parahippocampal gyrus as a multimodal association area in psychosis

Temporal lobe lesions may lead to schizophrenia-like psychosis, a phenomenon resembling psychotic disorders such as schizophrenia. We discuss a patient with a temporo-basal low-grade glioma presenting with bimodal hallucinosis (visual and auditory), a symptom set that is rarely described in psychotic disorders associated with morphological correlates. In light of a literature review of patients experiencing similar bimodal psychotic symptoms and electrophysiological data obtained in non-human primates, we suggest the parahippocampal gyrus to be a multimodal association area with bimodal units.

Positive association between cognitive ability and cortical thickness in a representative US sample of healthy 6 to 18 year-olds

Neuroimaging studies, using various modalities, have evidenced a link between the general intelligence factor (g) and regional brain function and structure in several multimodal association areas. While in the last few years, developments in computational neuroanatomy have made possible the in vivo quantification of cortical thickness, the relationship between cortical thickness and psychometric intelligence has been little studied. Recently, cortical thickness estimations have been improved by the use of an iterative hemisphere-specific template registration algorithm which provides a better between-subject alignment of brain surfaces. Using this improvement, we aimed to further characterize brain regions where cortical thickness was associated with cognitive ability differences and to test the hypothesis that these regions are mostly located in multimodal association areas. We report associations between a general cognitive ability factor (as an estimate of g) derived from the four subtests of the Wechsler Abbreviated Scale of Intelligence and cortical thickness adjusted for age, gender, and scanner in a large sample of healthy children and adolescents (ages 6-18, N=216) representative of the US population. Significant positive associations were evidenced between the cognitive ability factor and cortical thickness in most multimodal association areas. Results are consistent with a distributed model of intelligence.