Showing papers in "Cerebral Cortex in 2009"

Where Is the Semantic System? A Critical Review and Meta-Analysis of 120 Functional Neuroimaging Studies

Abstract: Semantic memory refers to knowledge about people, objects, actions, relations, self, and culture acquired through experience. The neural systems that store and retrieve this information have been studied for many years, but a consensus regarding their identity has not been reached. Using strict inclusion criteria, we analyzed 120 functional neuroimaging studies focusing on semantic processing. Reliable areas of activation in these studies were identified using the activation likelihood estimate (ALE) technique. These activations formed a distinct, left-lateralized network comprised of 7 regions: posterior inferior parietal lobe, middle temporal gyrus, fusiform and parahippocampal gyri, dorsomedial prefrontal cortex, inferior frontal gyrus, ventromedial prefrontal cortex, and posterior cingulate gyrus. Secondary analyses showed specific subregions of this network associated with knowledge of actions, manipulable artifacts, abstract concepts, and concrete concepts. The cortical regions involved in semantic processing can be grouped into 3 broad categories: posterior multimodal and heteromodal association cortex, heteromodal prefrontal cortex, and medial limbic regions. The expansion of these regions in the human relative to the nonhuman primate brain may explain uniquely human capacities to use language productively, plan, solve problems, and create cultural and technological artifacts, all of which depend on the fluid and efficient retrieval and manipulation of semantic knowledge.

Resting-State Functional Connectivity Reflects Structural Connectivity in the Default Mode Network

Abstract: Resting-state functional connectivity magnetic resonance imaging (fcMRI) studies constitute a growing proportion of functional brain imaging publications. This approach detects temporal correlations in spontaneous blood oxygen level--dependent (BOLD) signal oscillations while subjects rest quietly in the scanner. Although distinct resting-state networks related to vision, language, executive processing, and other sensory and cognitive domains have been identified, considerable skepticism remains as to whether resting-state functional connectivity maps reflect neural connectivity or simply track BOLD signal correlations driven by nonneural artifact. Here we combine diffusion tensor imaging (DTI) tractography with resting-state fcMRI to test the hypothesis that resting-state functional connectivity reflects structural connectivity. These 2 modalities were used to investigate connectivity within the default mode network, a set of brain regions—including medial prefrontal cortex (MPFC), medial temporal lobes (MTLs), and posterior cingulate cortex (PCC)/retropslenial cortex (RSC)—implicated in episodic memory processing. Using seed regions from the functional connectivity maps, the DTI analysis revealed robust structural connections between the MTLs and the retrosplenial cortex whereas tracts from the MPFC contacted the PCC (just rostral to the RSC). The results demonstrate that resting-state functional connectivity reflects structural connectivity and that combining modalities can enrich our understanding of these canonical brain networks.

Distinct Genetic Influences on Cortical Surface Area and Cortical Thickness

Abstract: Neuroimaging studies examining the effects of aging and neuropsychiatric disorders on the cerebral cortex have largely been based on measures of cortical volume. Given that cortical volume is a product of thickness and surface area, it is plausible that measures of volume capture at least 2 distinct sets of genetic influences. The present study aims to examine the genetic relationships between measures of cortical surface area and thickness. Participants were men in the Vietnam Era Twin Study of Aging (110 monozygotic pairs and 92 dizygotic pairs). Mean age was 55.8 years (range: 51-59). Bivariate twin analyses were utilized in order to estimate the heritability of cortical surface area and thickness, as well as their degree of genetic overlap. Total cortical surface area and average cortical thickness were both highly heritable (0.89 and 0.81, respectively) but were essentially unrelated genetically (genetic correlation = 0.08). This pattern was similar at the lobar and regional levels of analysis. These results demonstrate that cortical volume measures combine at least 2 distinct sources of genetic influences. We conclude that using volume in a genetically informative study, or as an endophenotype for a disorder, may confound the underlying genetic architecture of brain structure.

Mapping Anatomical Connectivity Patterns of Human Cerebral Cortex Using In Vivo Diffusion Tensor Imaging Tractography

Abstract: The characterization of the topological architecture of complex networks underlying the structural and functional organization of the brain is a basic challenge in neuroscience. However, direct evidence for anatomical connectivity networks in the human brain remains scarce. Here, we utilized diffusion tensor imaging deterministic tractography to construct a macroscale anatomical network capturing the underlying common connectivity pattern of human cerebral cortex in a large sample of subjects (80 young adults) and further quantitatively analyzed its topological properties with graph theoretical approaches. The cerebral cortex was divided into 78 cortical regions, each representing a network node, and 2 cortical regions were considered connected if the probability of fiber connections exceeded a statistical criterion. The topological parameters of the established cortical network (binarized) resemble that of a ‘‘small-world’’ architecture characterized by an exponentially truncated power-law distribution. These characteristics imply high resilience to localized damage. Furthermore, this cortical network was characterized by major hub regions in association cortices that were connected by bridge connections following long-range white matter pathways. Our results are compatible with previous structural and functional brain networks studies and provide insight into the organizational principles of human brain anatomical networks that underlie functional states.

The Resting Brain: Unconstrained yet Reliable

Abstract: Recent years have witnessed an upsurge in the usage of resting-state functional magnetic resonance imaging (fMRI) to examine functional connectivity (fcMRI), both in normal and pathological populations. Despite this increasing popularity, concerns about the psychologically unconstrained nature of the “resting-state” remain. Across studies, the patterns of functional connectivity detected are remarkably consistent. However, the test–retest reliability for measures of resting state fcMRI measures has not been determined. Here, we quantify the test–retest reliability, using resting scans from 26 participants at 3 different time points. Specifically, we assessed intersession (>5 months apart), intrasession ( nonsignificant), 2) correlation valence (positive > negative), and 3) network membership (default mode > task positive network). Short- and long-term measures of the consistency of global connectivity patterns were highly robust. Finally, hierarchical clustering solutions were highly reproducible, both across participants and sessions. Our findings provide a solid foundation for continued examination of resting state fcMRI in typical and atypical populations.

The Cortical Signature of Alzheimer's Disease: Regionally Specific Cortical Thinning Relates to Symptom Severity in Very Mild to Mild AD Dementia and is Detectable in Asymptomatic Amyloid-Positive Individuals

Abstract: Alzheimer's disease (AD) is associated with neurodegeneration in vulnerable limbic and heteromodal regions of the cerebral cortex, detectable in vivo using magnetic resonance imaging. It is not clear whether abnormalities of cortical anatomy in AD can be reliably measured across different subject samples, how closely they track symptoms, and whether they are detectable prior to symptoms. An exploratory map of cortical thinning in mild AD was used to define regions of interest that were applied in a hypothesis-driven fashion to other subject samples. Results demonstrate a reliably quantifiable in vivo signature of abnormal cortical anatomy in AD, which parallels known regional vulnerability to AD neuropathology. Thinning in vulnerable cortical regions relates to symptom severity even in the earliest stages of clinical symptoms. Furthermore, subtle thinning is present in asymptomatic older controls with brain amyloid binding as detected with amyloid imaging. The reliability and clinical validity of AD-related cortical thinning suggests potential utility as an imaging biomarker. This “disease signature” approach to cortical morphometry, in which disease effects are mapped across the cortical mantle and then used to define ROIs for hypothesis-driven analyses, may provide a powerful methodological framework for studies of neuropsychiatric diseases.

Segregated Fronto-Cerebellar Circuits Revealed by Intrinsic Functional Connectivity

Abstract: Multiple, segregated fronto-cerebellar circuits have been characterized in nonhuman primates using transneuronal tracing techniques including those that target prefrontal areas. Here, we used functional connectivity MRI (fcMRI) in humans (n = 40) to identify 4 topographically distinct fronto-cerebellar circuits that target 1) motor cortex, 2) dorsolateral prefrontal cortex, 3) medial prefrontal cortex, and 4) anterior prefrontal cortex. All 4 circuits were replicated and dissociated in an independent data set (n = 40). Direct comparison of right- and left-seeded frontal regions revealed contralateral lateralization in the cerebellum for each of the segregated circuits. The presence of circuits that involve prefrontal regions confirms that the cerebellum participates in networks important to cognition including a specific fronto-cerebellar circuit that interacts with the default network. Overall, the extent of the cerebellum associated with prefrontal cortex included a large portion of the posterior hemispheres consistent with a prominent role of the cerebellum in nonmotor functions. We conclude by providing a provisional map of the topography of the cerebellum based on functional correlations with the frontal cortex.

The Observation and Execution of Actions Share Motor and Somatosensory Voxels in all Tested Subjects: Single-Subject Analyses of Unsmoothed fMRI Data

Abstract: Many neuroimaging studies of the mirror neuron system (MNS) examine if certain voxels in the brain are shared between action observation and execution (shared voxels, sVx). Unfortunately, finding sVx in standard group analyses is not a guarantee that sVx exist in individual subjects. Using unsmoothed, single-subject analyses we show sVx can be reliably found in all 16 investigated participants. Beside the ventral premotor (BA6/44) and inferior parietal cortex (area PF) where mirror neurons (MNs) have been found in monkeys, sVx were reliably observed in dorsal premotor, supplementary motor, middle cingulate, somatosensory (BA3, BA2, and OP1), superior parietal, middle temporal cortex and cerebellum. For the premotor, somatosensory and parietal areas, sVx were more numerous in the left hemisphere. The hand representation of the primary motor cortex showed a reduced BOLD during hand action observation, possibly preventing undesired overt imitation. This study provides a more detailed description of the location and reliability of sVx and proposes a model that extends the original idea of the MNS to include forward and inverse internal models and motor and sensory simulation, distinguishing the MNS from a more general concept of sVx.

Musical Training Influences Linguistic Abilities in 8-Year-Old Children: More Evidence for Brain Plasticity

Abstract: We conducted a longitudinal study with 32 nonmusician children over 9 months to determine 1) whether functional differences between musician and nonmusician children reflect specific predispositions for music or result from musical training and 2) whether musical training improves nonmusical brain functions such as reading and linguistic pitch processing. Event-related brain potentials were recorded while 8-year-old children performed tasks designed to test the hypothesis that musical training improves pitch processing not only in music but also in speech. Following the first testing sessions nonmusician children were pseudorandomly assigned to music or to painting training for 6 months and were tested again after training using the same tests. After musical (but not painting) training, children showed enhanced reading and pitch discrimination abilities in speech. Remarkably, 6 months of musical training thus suffices to significantly improve behavior and to influence the development of neural processes as reflected in specific pattern of brain waves. These results reveal positive transfer from music to speech and highlight the influence of musical training. Finally, they demonstrate brain plasticity in showing that relatively short periods of training have strong consequences on the functional organization of the children's brain.

High Consistency of Regional Cortical Thinning in Aging across Multiple Samples

Abstract: Cross-sectional magnetic resonance imaging (MRI) studies of cortical thickness and volume have shown age effects on large areas, but there are substantial discrepancies across studies regarding the localization and magnitude of effects. These discrepancies hinder understanding of effects of aging on brain morphometry, and limit the potential usefulness of MR in research on healthy and pathological age-related brain changes. The present study was undertaken to overcome this problem by assessing the consistency of age effects on cortical thickness across 6 different samples with a total of 883 participants. A surface-based segmentation procedure (FreeSurfer) was used to calculate cortical thickness continuously across the brain surface. The results showed consistent age effects across samples in the superior, middle, and inferior frontal gyri, superior and middle temporal gyri, precuneus, inferior and superior parietal cortices, fusiform and lingual gyri, and the temporo-parietal junction. The strongest effects were seen in the superior and inferior frontal gyri, as well as superior parts of the temporal lobe. The inferior temporal lobe and anterior cingulate cortices were relatively less affected by age. The results are discussed in relation to leading theories of cognitive aging.

Development of Anterior Cingulate Functional Connectivity from Late Childhood to Early Adulthood

Abstract: Human cerebral development is remarkably protracted. Although microstructural processes of neuronal maturation remain accessible only to morphometric post-mortem studies, neuroimaging tools permit the examination of macrostructural aspects of brain development. The analysis of resting-state functional connectivity (FC) offers novel possibilities for the investigation of cerebral development. Using seed-based FC methods, we examined the development of 5 functionally distinct cingulate-based intrinsic connectivity networks (ICNs) in children (n 5 14, 10.6 6 1.5 years), adolescents (n 5 12, 15.4 6 1.2) and young adults (n514, 22.4 6 1.2). Children demonstrated a more diffuse pattern of correlation with voxels proximal to the seed region of interest (ROI) (‘‘local FC’’), whereas adults exhibited more focal patterns of FC, as well as a greater number of significantly correlated voxels at long distances from the seed ROI. Adolescents exhibited intermediate patterns of FC. Consistent with evidence for different maturational time courses, ICNs associated with social and emotional functions exhibited the greatest developmental effects. Our findings demonstrate the utility of FC for the study of developing functional organization. Moreover, given that ICNs are thought to have an anatomical basis in neuronal connectivity, measures of FC may provide a quantitative index of brain maturation in healthy subjects and those with neurodevelopmental disorders.

REM Sleep, Prefrontal Theta, and the Consolidation of Human Emotional Memory

Abstract: Both emotion and sleep are independently known to modulate declarative memory. Memory can be facilitated by emotion, leading to enhanced consolidation across increasing time delays. Sleep also facilitates offline memory processing, resulting in superior recall the next day. Here we explore whether rapid eye movement (REM) sleep, and aspects of its unique neurophysiology, underlie these convergent influences on memory. Using a nap paradigm, we measured the consolidation of neutral and negative emotional memories, and the association with REM-sleep electrophysiology. Subjects that napped showed a consolidation benefit for emotional but not neutral memories. The No-Nap control group showed no evidence of a consolidation benefit for either memory type. Within the Nap group, the extent of emotional memory facilitation was significantly correlated with the amount of REM sleep and also with right-dominant prefrontal theta power during REM. Together, these data support the role of REM-sleep neurobiology in the consolidation of emotional human memories, findings that have direct translational implications for affective psychiatric and mood disorders.

Sensitivity of the Action Observation Network to Physical and Observational Learning

Abstract: Human motor skills can be acquired by observation without the benefit of immediate physical practice. The current study tested if physical rehearsal and observational learning share common neural substrates within an action observation network (AON) including premotor and inferior parietal regions, that is, areas activated both for execution and observation of similar actions. Participants trained for 5 days on dance sequences set to music videos. Each day they physically rehearsed one set of dance sequences (“danced”), and passively watched a different set of sequences (“watched”). Functional magnetic resonance imaging was obtained prior to and immediately following the 5 days of training. After training, a subset of the AON showed a degree of common activity for observational and physical learning. Activity in these premotor and parietal regions was sustained during observation of sequences that were danced or watched, but declined for unfamiliar sequences relative to the pretraining scan session. These imaging data demonstrate the emergence of action resonance processes in the human brain based on observational learning without physical practice and identify commonalities in the neural substrates for physical and observational learning.

Grasping Ideas with the Motor System: Semantic Somatotopy in Idiom Comprehension

Abstract: Single words and sentences referring to bodily actions activate the motor cortex. However, this semantic grounding of concrete language does not address the critical question whether the sensory--motor system contributes to the processing of abstract meaning and thought. We examined functional magnetic resonance imaging activation to idioms and literal sentences including armand leg-related action words. A common left fronto-temporal network was engaged in sentence reading, with idioms yielding relatively stronger activity in (pre)frontal and middle temporal cortex. Crucially, somatotopic activation along the motor strip, in central and precentral cortex, was elicited by idiomatic and literal sentences, reflecting the body part reference of the words embedded in the sentences. Semantic somatotopy was most pronounced after sentence ending, thus reflecting sentence-level processing rather than that of single words. These results indicate that semantic representations grounded in the sensory--motor system play a role in the composition of sentence-level meaning, even in the case of idioms.

Sex Differences and the Impact of Steroid Hormones on the Developing Human Brain

Abstract: Little is known about the hormonal effects of puberty on the anatomy of the developing human brain. In a voxel-based morphometry study, sex-related differences in gray matter (GM) volume were examined in 46 subjects aged 8-15 years. Males had larger GM volumes in the left amygdala, whereas females had larger right striatal and bilateral hippocampal GM volumes than males. Sexually dimorphic areas were related to Tanner stages (TS) of pubertal development and to circulating level of steroid hormones in a subsample of 30 subjects. Regardless of sex, amygdala and hippocampal volumes varied as a function of TS and were associated with circulating testosterone (TEST) levels. By contrast, striatal GM volumes were unrelated to pubertal development and circulating steroid hormones. Whole-brain regression analyses revealed positive associations between circulating estrogen levels and parahippocampal GM volumes as well as between TEST levels and diencephalic brain structures. In addition, a negative association was found between circulating TEST and left parietal GM volumes. These data suggest that GM development in certain brain regions is associated with sexual maturation and that pubertal hormones might have organizational effects on the developing human brain.

Determining a Role for Ventromedial Prefrontal Cortex in Encoding Action-Based Value Signals During Reward-Related Decision Making

Abstract: Considerable evidence has emerged to implicate ventromedial prefrontal cortex in encoding expectations of future reward during value-based decision making. However, the nature of the learned associations upon which such representations depend is much less clear. Here, we aimed to determine whether expected reward representations in this region could be driven by action–outcome associations, rather than being dependent on the associative value assigned to particular discriminative stimuli. Subjects were scanned with functional magnetic resonance imaging while performing 2 variants of a simple reward-related decision task. In one version, subjects made choices between 2 different physical motor responses in the absence of discriminative stimuli, whereas in the other version, subjects chose between 2 different stimuli that were randomly assigned to different responses on a trial-by-trial basis. Using an extension of a reinforcement learning algorithm, we found activity in ventromedial prefrontal cortex tracked expected future reward during the action-based task as well as during the stimulus-based task, indicating that value representations in this region can be driven by action–outcome associations. These findings suggest that ventromedial prefrontal cortex may play a role in encoding the value of chosen actions irrespective of whether those actions denote physical motor responses or more abstract decision options.

Intermediate neuronal progenitors (basal progenitors) produce pyramidal-projection neurons for all layers of cerebral cortex.

Abstract: The developing cerebral cortex contains apical and basal types of neurogenic progenitor cells. Here, we investigated the cellular properties and neurogenic output of basal progenitors, also called intermediate neuronal progenitors (INPs). We found that basal mitoses expressing transcription factor Tbr2 (an INP marker) were present throughout corticogenesis, from embryonic day 10.5 through birth. Postnatally, Tbr2+ progenitors were present in the dentate gyrus, subventricular zone (SVZ), and posterior periventricle (pPV). Two morphological subtypes of INPs were distinguished in the embryonic cortex, “short radial” in the ventricular zone (VZ) and multipolar in the SVZ, probably corresponding to molecularly defined INP subtypes. Unexpectedly, many short radial INPs appeared to contact the apical (ventricular) surface and some divided there. Time-lapse video microscopy suggested that apical INP divisions produced daughter INPs. Analysis of neurogenic divisions (Tis21-green fluorescent protein [GFP]+) indicated that INPs may produce the majority of projection neurons for preplate, deep, and superficial layers. Conversely, proliferative INP divisions (Tis21-GFP−) increased from early to middle corticogenesis, concomitant with SVZ growth. Our findings support the hypothesis that regulated amplification of INPs may be an important factor controlling the balance of neurogenesis among different cortical layers.

Neuroanatomical correlates of musicianship as revealed by cortical thickness and voxel-based morphometry.

Abstract: We used a multimethod approach to investigate the neuroanatomical correlates of musicianship and absolute pitch (AP). Cortical thickness measures, interregional correlations applied to these thicknesses, and voxel-based morphometry (VBM) were applied to the same magnetic resonance imaging data set of 71 musicians (27 with AP) and 64 nonmusicians. Cortical thickness was greater in musicians with peaks in superior temporal and dorsolateral frontal regions. Correlations between 2 seed points, centered on peaks of thickness difference within the right frontal cortex, and all other points across the cortex showed greater specificity of significant correlations among musicians, with fewer and more discrete areas correlating with the frontal seeds, including the superior temporal cortex. VBM of gray matter (GM)-classified voxels yielded a strongly right-lateralized focus of greater GM concentration in musicians centered on the posterolateral aspect of Heschl's gyrus. Together, these results are consistent with functional evidence emphasizing the importance of a frontotemporal network of areas heavily relied upon in the performance of musical tasks. Among musicians, contrasts of AP possessors and nonpossessors showed significantly thinner cortex among possessors in a number of areas, including the posterior dorsal frontal cortices that have been previously implicated in the performance of AP tasks.

The Contributions of Prefrontal Cortex and Executive Control to Deception: Evidence from Activation Likelihood Estimate Meta-analyses

Abstract: Previous neuroimaging studies have implicated the prefrontal cortex (PFC) and nearby brain regions in deception. This is consistent with the hypothesis that lying involves the executive control system. To date, the nature of the contribution of different aspects of executive control to deception, however, remains unclear. In the present study, we utilized an activation likelihood estimate (ALE) method of meta-analysis to quantitatively identify brain regions that are consistently more active for deceptive responses relative to truthful responses across past studies. We then contrasted the results with additional ALE maps generated for 3 different aspects of executive control: working memory, inhibitory control, and task switching. Deception-related regions in dorsolateral PFC and posterior parietal cortex were selectively associated with working memory. Additional deception regions in ventrolateral PFC, anterior insula, and anterior cingulate cortex were associated with multiple aspects of executive control. In contrast, deception-related regions in bilateral inferior parietal lobule were not associated with any of the 3 executive control constructs. Our findings support the notion that executive control processes, particularly working memory, and their associated neural substrates play an integral role in deception. This work provides a foundation for future research on the neurocognitive basis of deception.

A Dual Role for Prediction Error in Associative Learning

Abstract: Confronted with a rich sensory environment, the brain must learn statistical regularities across sensory domains to construct causal models of the world. Here, we used functional magnetic resonance imaging and dynamic causal modeling (DCM) to furnish neurophysiological evidence that statistical associations are learnt, even when task-irrelevant. Subjects performed an audio-visual target-detection task while being exposed to distractor stimuli. Unknown to them, auditory distractors predicted the presence or absence of subsequent visual distractors. We modeled incidental learning of these associations using a Rescorla-Wagner (RW) model. Activity in primary visual cortex and putamen reflected learning-dependent surprise: these areas responded progressively more to unpredicted, and progressively less to predicted visual stimuli. Critically, this prediction-error response was observed even when the absence of a visual stimulus was surprising. We investigated the underlying mechanism by embedding the RW model into a DCM to show that auditory to visual connectivity changed significantly over time as a function of prediction error. Thus, consistent with predictive coding models of perception, associative learning is mediated by prediction-error dependent changes in connectivity. These results posit a dual role for prediction-error in encoding surprise and driving associative plasticity.

Brain Oscillations Dissociate between Semantic and Nonsemantic Encoding of Episodic Memories

Abstract: Prior studies, mostly using intentional learning, suggest that power increases in theta and gamma oscillations and power decreases in alpha and beta oscillations are positively related to later remembering. Using incidental learning, this study investigated whether these brain oscillatory subsequent memory effects can be differentiated by encoding task. One group of subjects studied material performing a semantic (deep) encoding task, whereas the other group studied the same material performing a nonsemantic (shallow) encoding task. Successful encoding in the semantic task was related to power decreases in the alpha (8-12 Hz) and beta (12-20 Hz) frequency band, and a power increase in the gamma band (55-70 Hz). In the shallow task, successful encoding was related to a power decrease in the alpha band and a power increase in the theta frequency band (4-7 Hz). A direct comparison of results between the 2 encoding tasks revealed that semantic subsequent memory effects were specifically reflected by power decreases in the beta (0.5-1.5 s) and the alpha frequency band (0.5-1.0 s), whereas nonsemantic subsequent memory effects were specifically reflected by a power increase in the theta frequency band (0.5-1.0 s).

The Neural Basis of Human Social Values: Evidence from Functional MRI

Abstract: Social values are composed of social concepts (e.g., “generosity”) and context-dependent moral sentiments (e.g., “pride”). The neural basis of this intricate cognitive architecture has not been investigated thus far. Here, we used functional magnetic resonance imaging while subjects imagined their own actions toward another person (self-agency) which either conformed or were counter to a social value and were associated with pride or guilt, respectively. Imagined actions of another person toward the subjects (other-agency) in accordance with or counter to a value were associated with gratitude or indignation/anger. As hypothesized, superior anterior temporal lobe (aTL) activity increased with conceptual detail in all conditions. During self-agency, activity in the anterior ventromedial prefrontal cortex correlated with pride and guilt, whereas activity in the subgenual cingulate solely correlated with guilt. In contrast, indignation/anger activated lateral orbitofrontal-insular cortices. Pride and gratitude additionally evoked mesolimbic and basal forebrain activations. Our results demonstrate that social values emerge from coactivation of stable abstract social conceptual representations in the superior aTL and context-dependent moral sentiments encoded in fronto-mesolimbic regions. This neural architecture may provide the basis of our ability to communicate about the meaning of social values across cultural contexts without limiting our flexibility to adapt their emotional interpretation.

Conceptual Knowledge Is Underpinned by the Temporal Pole Bilaterally: Convergent Evidence from rTMS

Abstract: Conceptual knowledge provides the basis on which we bring meaning to our world. Studies of semantic dementia patients and some functional neuroimaging studies indicate that the anterior temporal lobes, bilaterally, are the core neural substrate for the formation of semantic representations. This hypothesis remains controversial, however, as traditional neurological models of comprehension do not posit a role for these regions. To adjudicate on this debate, we conducted 2 novel experiments that used off-line, low-frequency, repetitive transcranial magnetic stimulation to disrupt neural processing temporarily in the left or right temporal poles (TPs). The time required to make semantic decisions was slowed considerably, yet specifically, by this procedure. The results confirm that both TPs form a critical substrate within the neural network that supports conceptual knowledge.

Striatal Dopamine and Working Memory

Abstract: Recent studies have emphasized the importance of dopamine projections to the prefrontal cortex (PFC) for working memory (WM) function, although this system has rarely been studied in humans in vivo. However, dopamine and PFC activity can be directly measured with positron emission tomography (PET) and functional magnetic resonance imaging (fMRI), respectively. In this study, we examined WM capacity, dopamine, and PFC function in healthy older participants in order to test the hypothesis that there is a relationship between these 3 factors. We used the PET tracer 6-[18F]fluoro-L-m-tyrosine to measure dopamine synthesis capacity in the striatum (caudate, putamen), and event-related fMRI to measure brain activation during different epochs (cue, delay, probe) of a WM task. Caudate (but not putamen) dopamine correlated positively with WM capacity, whereas putamen (but not caudate) dopamine correlated positively with motor speed. In addition, delay-related fMRI activation in a left inferior prefrontal region was related to both caudate dopamine and task accuracy, suggesting that this may be a critical site for the integration of WM maintenance processes. These results provide new evidence that striatal dopaminergic function is related to PFC-dependent functions, particularly brain activation and behavioral performance during WM tasks.

Characterization of Nkx6-2-Derived Neocortical Interneuron Lineages

Abstract: Ventral telencephalic progenitors expressing the homeodomain transcription factor Nkx6-2 have been shown to give rise to a multitude of cortical interneuron subtypes usually associated with origin in either the medial ganglionic eminence or the caudal ganglionic eminence. The function of Nkx6-2 in directing the fate of those progenitors has, however, not been thoroughly analyzed. We used a combination of genetic inducible fate mapping and in vivo loss-of-function to analyze the requirement of Nkx6-2 in determining the fate of cortical interneurons. We have found that interneuron subtypes are born with a characteristic temporal pattern. Furthermore, we extend the characterization of interneurons from the Nkx6-2 lineage through the application of electrophysiological methods. Analysis of these populations in Nkx6-2 null mice suggests that there is a small and partially penetrant loss of delayed non-fast spiking somatostatin/calretinin double positive cortical interneurons in the absence of Nkx6-2 gene function.

The Neural Architecture of Music-Evoked Autobiographical Memories

Abstract: The medial prefrontal cortex (MPFC) is regarded as a region of the brain that supports self-referential processes, including the integration of sensory information with self-knowledge and the retrieval of autobiographical information. I used functional magnetic resonance imaging and a novel procedure for eliciting autobiographical memories with excerpts of popular music dating to one's extended childhood to test the hypothesis that music and autobiographical memories are integrated in the MPFC. Dorsal regions of the MPFC (Brodmann area 8/9) were shown to respond parametrically to the degree of autobiographical salience experienced over the course of individual 30 s excerpts. Moreover, the dorsal MPFC also responded on a second, faster timescale corresponding to the signature movements of the musical excerpts through tonal space. These results suggest that the dorsal MPFC associates music and memories when we experience emotionally salient episodic memories that are triggered by familiar songs from our personal past. MPFC acted in concert with lateral prefrontal and posterior cortices both in terms of tonality tracking and overall responsiveness to familiar and autobiographically salient songs. These findings extend the results of previous autobiographical memory research by demonstrating the spontaneous activation of an autobiographical memory network in a naturalistic task with low retrieval demands.

Functional Dissociation in Right Inferior Frontal Cortex during Performance of Go/No-Go Task

Abstract: The contribution of the right inferior frontal cortex to response inhibition has been demonstrated by previous studies of neuropsychology, electrophysiology, and neuroimaging. The inferior frontal cortex is also known to be activated during processing of infrequent stimuli such as stimulus-driven attention. Response inhibition has most often been investigated using the go/no-go task, and the no-go trials are usually given infrequently to enhance prepotent response tendency. Thus, it has not been clarified whether the inferior frontal activation during the go/no-go task is associated with response inhibition or processing of infrequent stimuli. In the present functional magnetic resonance imaging study, we employed not only frequent-go trials but also infrequent-go trials that were presented as infrequently as the no-go trials. The imaging results demonstrated that the posterior inferior frontal gyrus (pIFG) was activated during response inhibition as revealed by the no-go vs. infrequent-go trials, whereas the inferior frontal junction (IFJ) region was activated primarily during processing of infrequent stimuli as revealed by the infrequent-go versus frequent-go trials. These results indicate that the pIFG and IFJ within the inferior frontal cortex are spatially close but are associated with different cognitive control processes in the go/no-go paradigm.

Reading and Subcortical Auditory Function

Abstract: Although it is largely agreed that phonological processing deficits are a major cause of poor reading, the neural origins of phonological processing are not well understood. We now show, for the first time, that phonological decoding, measured with a test of single-nonword reading, is significantly correlated with the timing of subcortical auditory processing and also, to a lesser extent, with the robustness of subcortical representation of the harmonic content of speech, but not with pitch encoding. The relationships we observe between reading and subcortical processing fall along a continuum, with poor readers at one end and good readers at the other. These data suggest that reading skill may depend on the integrity of subcortical auditory mechanisms and are consistent with the idea that subcortical representation of the acoustic features of speech may play a role in normal reading as well as in the development of reading disorders. These data establish a significant link between subcortical auditory function and reading, thereby contributing to the understanding of the biological bases of reading. At a more general level, these findings are among the first to establish a direct relationship between subcortical sensory function and a specific cognitive skill (reading). We argue that this relationship between cortical and subcortical function could be shaped during development by the corticofugal pathway and that this cortical–subcortical link could contribute to the phonological processing deficits experienced by poor readers.

Structural Asymmetries in the Infant Language and Sensori-Motor Networks

Abstract: Both language capacity and strongly lateralized hand preference are among the most intriguing particularities of the human species. They are associated in the adult brain with functional and anatomical hemispheric asymmetries in the speech perceptionproduction network and in the sensori-motor system. Only studies in early life can help us to understand how such asymmetries arise during brain development, and to which point structural left--right differences are the source or the consequence of functional lateralization. In this study, we aimed to provide new in vivo structural markers of hemispheric asymmetries in infants from 1 to 4 months of age, with diffusion tensor imaging. We used 3 complementary analysis methods based on local diffusion indices and spatial localizations of tracts. After a prospective approach over the whole brain, we demonstrated early leftward asymmetries in the arcuate fasciculus and in the cortico-spinal tract. These results suggest that the early macroscopic geometry, microscopic organization, and maturation of these white matter bundles are related to the development of later functional lateralization.

Two Types of Thalamocortical Projections from the Motor Thalamic Nuclei of the Rat: A Single Neuron-Tracing Study Using Viral Vectors

Abstract: The axonal arborization of single motor thalamic neurons was examined in rat brain using a viral vector expressing membrane-targeted palmitoylation site-attached green fluorescent protein (palGFP). We first divided the ventral anterior-ventral lateral motor thalamic nuclei into 1) the rostromedial portion, which was designated inhibitory afferent-dominant zone (IZ) with intense glutamate decarboxylase immunoreactivity and weak vesicular glutamate transporter 2 immunoreactivity, and 2) the caudolateral portion, named excitatory subcortical afferent-dominant zone (EZ) with the reversed immunoreactivity profile. We then labeled 38 motor thalamic neurons in 29 hemispheres by injecting a diluted palGFP-Sindbis virus solution and isolated 10 IZ and EZ neurons for reconstruction. All the reconstructed IZ neurons widely projected not only to the cerebral cortex but also to the neostriatum, whereas the EZ neurons sent axons almost exclusively to the cortex. More interestingly, 47-66% of axon varicosities of IZ neurons were observed in layer I of cortical areas. In contrast, only 2-15% of varicosities of EZ neurons were found in layer I, most varicosities being located in middle layers. These results suggest that 2 forms of information from the basal ganglia and cerebellum are differentially supplied to apical and basal dendrites, respectively, of cortical pyramidal neurons and integrated to produce a motor execution command.