Cerebral Cortex - current issue

Studying the Neurobiology of Social Interaction with Transcranial Direct Current Stimulation--The Example of Punishing Unfairness

2008-08-15

Studying social behavior often requires the simultaneous interaction of many subjects. As yet, however, no painless, noninvasive brain stimulation tool existed that allowed the simultaneous affection of brain processes in many interacting subjects. Here we show that transcranial direct current stimulation (tDCS) can overcome these limits. We apply right prefrontal cathodal tDCS and show that subjects’ propensity to punish unfair behavior is reduced significantly.

Fundamental Requirements for Primary Visual Perception

Pollen, D. A. — 2008-08-15

A novel perspective for the necessary and sufficient conditions for primary visual perception is proposed based upon relating recent discoveries from the visual sciences to relevant foundational neurological observations. This analysis suggests that a fundamental requirement for the emergence of normal primary visual perception is the coupling between the early visual cortices in the occipital lobe subserving image content with specific areas in the parietal lobe subserving selective attention, representations of extrapersonal space, the body schema, and the initiation of perceptual ownership. Fully intact primary visual perception, which includes the normal placement of image content within extrapersonal space, seems to require at each instant a mutually consistent completeness and corresponding removal of ambiguities in each of the linked neural representations subserving image, space and self. Experimental approaches that could either invalidate or strengthen the proposed framework are suggested as well as opportunities to differentiate some aspects of normal primary visual perception from the severely compromised visual experience that survives bilateral parieto-occipital lesions (Balint's syndrome) when visual experience may persist for single but unlocalizable objects.

The Central Sulcus: an Observer-Independent Characterization of Sulcal Landmarks and Depth Asymmetry

2008-08-15

Studies of the central sulcus (CS) often use observer-dependent procedures to assess CS morphology and sulcal landmarks. Here, we applied a novel method combining automated sulcus reconstruction, surface parameterization, and an observer-independent depth measurement to study the CS. This facilitated the quantitative assessment of the spatial position and intersubject variability of several sulcal landmarks. Sulcal depth profiles also allowed us to develop an algorithm for the clear identification of several landmarks, including the pli de passage fronto-pariétal moyen (PPFM), first described by Broca. Using this algorithm, the PPFM was identified in the majority of sulci, but exhibited limited spatial variability. This appears to support Cunningham's theory that this landmark may be a developmental remnant, and may argue against its role as a guide to the more variable somatotopic hand area. Sulcal depth profiles were also utilized to assess the influence of sex, handedness, and age on CS morphology. These profiles revealed leftward depth asymmetry in the superior extent of the CS of male subjects and near the midpoint of the CS in female subjects. Age correlations were performed for these asymmetries, and a significant correlation was seen only in the male subgroup.

Spontaneous Fluctuations in Posterior {alpha}-Band EEG Activity Reflect Variability in Excitability of Human Visual Areas

Romei, V., Brodbeck, V., Michel, C., Amedi, A., Pascual-Leone, A., Thut, G. — 2008-08-15

Neural activity fluctuates dynamically with time, and these changes have been reported to be of behavioral significance, despite occurring spontaneously. Through electroencephalography (EEG), fluctuations in -band (8–14 Hz) activity have been identified over posterior sites that covary on a trial-by-trial basis with whether an upcoming visual stimulus will be detected or not. These fluctuations are thought to index the momentary state of visual cortex excitability. Here, we tested this hypothesis by directly exciting human visual cortex via transcranial magnetic stimulation (TMS) to induce illusory visual percepts (phosphenes) in blindfolded participants, while simultaneously recording EEG. We found that identical TMS-stimuli evoked a percept (P-yes) or not (P-no) depending on prestimulus -activity. Low prestimulus -band power resulted in TMS reliably inducing phosphenes (P-yes trials), whereas high prestimulus -values led the same TMS-stimuli failing to evoke a visual percept (P-no trials). Additional analyses indicated that the perceptually relevant fluctuations in -activity/visual cortex excitability were spatially specific and occurred on a subsecond time scale in a recurrent pattern. Our data directly link momentary levels of posterior -band activity to distinct states of visual cortex excitability, and suggest that their spontaneous fluctuation constitutes a visual operation mode that is activated automatically even without retinal input.

Mapping the Relationship between Cortical Convolution and Intelligence: Effects of Gender

2008-08-15

The pronounced convolution of the human cortex may be a morphological substrate that supports some of our species’ most distinctive cognitive abilities. Therefore, individual intelligence within humans might be modulated by the degree of folding in certain cortical regions. We applied advanced methods to analyze cortical convolution at high spatial resolution and correlated those measurements with intelligence quotients. Within a large sample of healthy adult subjects (n = 65), we detected the most prominent correlations in the left medial hemisphere. More specifically, intelligence scores were positively associated with the degree of folding in the temporo-occipital lobe, particularly in the outermost section of the posterior cingulate gyrus (retrosplenial areas). Thus, this region might be an important contributor toward individual intelligence, either via modulating pathways to (pre)frontal regions or by serving as a location for the convergence of information. Prominent gender differences within the right frontal cortex were observed; females showed uncorrected significant positive correlations and males showed a nonsignificant trend toward negative correlations. It is possible that formerly described gender differences in regional convolution are associated with differences in the underlying architecture. This might lead to the development of sexually dimorphic information processing strategies and affect the relationship between intelligence and cortical convolution.

The Expression of Contextual Fear Conditioning Involves Activation of an NMDA Receptor-Nitric Oxide Pathway in the Medial Prefrontal Cortex

Moraes Resstel, L. B., de Aguiar Correa, F. M., Guimaraes, F. S. — 2008-08-15

The ventral portion of medial prefrontal cortex (vMPFC) is involved in contextual fear-conditioning expression in rats. In the present study, we investigated the role of local N-methyl-D-aspartic acid (NMDA) glutamate receptors and nitric oxide (NO) in vMPFC on the behavioral (freezing) and cardiovascular (increase of arterial pressure and heart rate) responses of rats exposed to a context fear conditioning. The results showed that both freezing and cardiovascular responses to contextual fear conditioning were reduced by bilateral administration of NMDA receptor antagonist LY235959 (4 nmol/200 nL) into the vMPFC before reexposition to conditioned chamber. Bilateral inhibition of neuronal NO synthase (nNOS) by local vMPFC administration of the N-propyl-L-arginine (N-propyl, 0.04 nmol/200 nL) or the NO scavenger carboxy-PTIO (1 nmol/200 nL) caused similar results, inhibiting the fear responses. We also investigated the effects of inhibiting glutamate- and NO-mediated neurotransmission in the vMPFC at the time of aversive context exposure on reexposure to the same context. It was observed that the 1st exposure results in a significant attenuation of the fear responses on reexposure in vehicle-treated animals, which was not modified by the drugs. The present results suggest that a vMPFC NMDA–NO pathway may play an important role on expression of contextual fear conditioning.

Discharge Synchrony during the Transition of Behavioral Goal Representations Encoded by Discharge Rates of Prefrontal Neurons

Sakamoto, K., Mushiake, H., Saito, N., Aihara, K., Yano, M., Tanji, J. — 2008-08-15

To investigate the temporal relationship between synchrony in the discharge of neuron pairs and modulation of the discharge rate, we recorded the neuronal activity of the lateral prefrontal cortex of monkeys performing a behavioral task that required them to plan an immediate goal of action to attain a final goal. Information about the final goal was retrieved via visual instruction signals, whereas information about the immediate goal was generated internally. The synchrony of neuron pair discharges was analyzed separately from changes in the firing rate of individual neurons during a preparatory period. We focused on neuron pairs that exhibited a representation of the final goal followed by a representation of the immediate goal at a later stage. We found that changes in synchrony and discharge rates appeared to be complementary at different phases of the behavioral task. Synchrony was maximized during a specific phase in the preparatory period corresponding to a transitional stage when the neuronal activity representing the final goal was replaced with that representing the immediate goal. We hypothesize that the transient increase in discharge synchrony is an indication of a process that facilitates dynamic changes in the prefrontal neural circuits in order to undergo profound state changes.

Depression of Human Corticospinal Excitability Induced by Magnetic Theta-burst Stimulation: Evidence of Rapid Polarity-Reversing Metaplasticity

Gentner, R., Wankerl, K., Reinsberger, C., Zeller, D., Classen, J. — 2008-08-15

Metaplasticity refers to the activity-dependent modification of the ability of synapses to undergo subsequent potentiation or depression, and is thought to maintain homeostasis of cortical excitability. Continuous magnetic theta-burst stimulation (cTBS; 50 Hz-bursts of 3 subthreshold magnetic stimuli repeated at 5 Hz) is a novel repetitive magnetic stimulation protocol used to model changes of synaptic efficacy in human motor cortex. Here we examined the influence of prior activity on the effects induced by cTBS. Without prior voluntary motor activation, application of cTBS for a duration of 20 s (cTBS300) facilitated subsequently evoked motor potentials (MEP) recorded from APB muscle. In contrast, MEP-size was depressed, when cTBS300 was preceded by voluntary activity of sufficient duration. Remarkably, even without prior voluntary activation, depression of MEP-size was induced when cTBS was extended over 40 s. These findings provide in vivo evidence for extremely rapid metaplasticity reversing potentiation of corticospinal excitability to depression. Polarity-reversing metaplasticity adds considerable complexity to the brain's response toward new experiences. Conditional dependence of cTBS-induced depression of corticospinal excitability on prior neuronal activation suggests that the TBS-model of synaptic plasticity may be closer to synaptic mechanisms than previously thought.

A Developmental fMRI Study of Reading and Repetition Reveals Changes in Phonological and Visual Mechanisms Over Age

Church, J. A., Coalson, R. S., Lugar, H. M., Petersen, S. E., Schlaggar, B. L. — 2008-08-15

In this study of reading development, children (ages 7–10) and adults (ages 18–32) performed overt single-word reading and aural repetition tasks on high-frequency word stimuli during functional magnetic resonance imaging. Most regions showed similar activity across age groups. These widespread regions of similarity indicate that children and adults use largely overlapping mechanisms when processing high-frequency words. Significant task-related differences included greater activity in occipital cortex for the read task, and greater activity in temporal cortex for the repeat task; activity levels in these regions were similar for adults and children. However, age group differences were found in several posterior regions, including a set of regions implicated in adult reading: the left supramarginal gyrus, the left angular gyrus, and bilateral anterior extrastriate cortex. The angular and supramarginal gyrus regions, hypothesized to play a role in phonology, showed decreased activity in adults relative to children for high-frequency words. The extrastriate regions had significant activity for both the visual read task and auditory repeat task in children, but just for the read task in adults, showing significant task and age interactions. These results are consistent with decreasing reliance on phonological processing, and increasing tuning of visual mechanisms, with age.

Do Cross-Modal Projections Always Result in Multisensory Integration?

2008-08-15

Convergence of afferents from different sensory modalities has generally been thought to produce bimodal (and trimodal) neurons (i.e., exhibit suprathreshold excitation to more than 1 sensory modality). Consequently, studies identifying cross-modal connections assume that such convergence results in bimodal (or trimodal) neurons that produce familiar forms of multisensory integration: response enhancement or depression. The present study questioned that assumption by anatomically identifying a projection from ferret auditory to visual cortex Area 21. However, electrophysiological recording within Area 21 not only failed to identify a single bimodal neuron but also familiar forms of multisensory integration were not observed either. Instead, a small proportion of neurons (9%; 27/296) showed subthreshold multisensory integration, in which visual responses were significantly modulated by auditory inputs. Such subthreshold multisensory effects were enhanced by -aminobutyric acid antagonism, whereby a majority of neurons (87%; 20/23) now participated in a significant, multisensory population effect. Thus, multisensory convergence does not de facto result in bimodal (or trimodal) neurons or the traditional forms of multisensory integration. However, the fact that unimodal neurons exhibited a subthreshold form of multisensory integration not only affirms the relationship between convergence and integration but also expands our understanding of the functional repertoire of multisensory processing itself.

Remediation of Sleep-Deprivation-Induced Working Memory Impairment with fMRI-Guided Transcranial Magnetic Stimulation

2008-08-15

Repetitive transcranial magnetic stimulation (rTMS) was applied to test the role of selected cortical regions in remediating sleep-deprivation–induced deficits in visual working memory (WM) performance. Three rTMS targets were chosen using a functional magnetic resonance imaging (fMRI)–identified network associated with sleep-deprivation–induced WM performance impairment: 2 regions from the network (upper left middle occipital gyrus and midline parietal cortex) and 1 nonnetwork region (lower left middle occipital gyrus). Fifteen participants underwent total sleep deprivation for 48 h. rTMS was applied at 5 Hz during a WM task in a within-subject sham-controlled design. The rTMS to the upper-middle occipital site resulted in a reduction of the sleep-induced reaction time deficit without a corresponding decrease in accuracy, whereas stimulation at the other sites did not. Each subject had undergone fMRI scanning while performing the task both pre- and postsleep deprivation, and the degree to which each individual activated the fMRI network was measured. The degree of performance enhancement with upper-middle occipital rTMS correlated with the degree to which each individual failed to sustain network activation. No effects were found in a subset of participants who performed the same rTMS procedure after recovering from sleep deprivation, suggesting that the performance enhancements seen following sleep deprivation were state dependent.

The Dynamical Response Properties of Neocortical Neurons to Temporally Modulated Noisy Inputs In Vitro

Kondgen, H., Geisler, C., Fusi, S., Wang, X.-J., Luscher, H.-R., Giugliano, M. — 2008-08-15

Cortical neurons are often classified by current–frequency relationship. Such a static description is inadequate to interpret neuronal responses to time-varying stimuli. Theoretical studies suggested that single-cell dynamical response properties are necessary to interpret ensemble responses to fast input transients. Further, it was shown that input-noise linearizes and boosts the response bandwidth, and that the interplay between the barrage of noisy synaptic currents and the spike-initiation mechanisms determine the dynamical properties of the firing rate. To test these model predictions, we estimated the linear response properties of layer 5 pyramidal cells by injecting a superposition of a small-amplitude sinusoidal wave and a background noise. We characterized the evoked firing probability across many stimulation trials and a range of oscillation frequencies (1–1000 Hz), quantifying response amplitude and phase-shift while changing noise statistics. We found that neurons track unexpectedly fast transients, as their response amplitude has no attenuation up to 200 Hz. This cut-off frequency is higher than the limits set by passive membrane properties (~50 Hz) and average firing rate (~20 Hz) and is not affected by the rate of change of the input. Finally, above 200 Hz, the response amplitude decays as a power-law with an exponent that is independent of voltage fluctuations induced by the background noise.

Hearing Loss Prevents the Maturation of GABAergic Transmission in the Auditory Cortex

Kotak, V. C., Takesian, A. E., Sanes, D. H. — 2008-08-15

Inhibitory neurotransmission is a critical determinant of neuronal network gain and dynamic range, suggesting that network properties are shaped by activity during development. A previous study demonstrated that sensorineural hearing loss (SNHL) in gerbils leads to smaller inhibitory potentials in L2/3 pyramidal neurons in the thalamorecipient auditory cortex, ACx. Here, we explored the mechanisms that account for proper maturation of -amino butyric acid (GABA)ergic transmission. SNHL was induced at postnatal day (P) 10, and whole-cell voltage-clamp recordings were obtained from layer 2/3 pyramidal neurons in thalamocortical slices at P16–19. SNHL led to an increase in the frequency of GABAzine-sensitive (antagonist) spontaneous (s) and miniature (m) inhibitory postsynaptic currents (IPSCs), accompanied by diminished amplitudes and longer durations. Consistent with this, the amplitudes of minimum-evoked IPSCs were also reduced while their durations were longer. The 1- and β2/3 subunit–specific agonists zolpidem and loreclezole increased control but not SNHL sIPSC durations. To test whether SNHL affected the maturation of GABAergic transmission, sIPSCs were recorded at P10. These sIPSCs resembled the long SNHL sIPSCs. Furthermore, zolpidem and loreclezole were ineffective in increasing their durations. Together, these data strongly suggest that the presynaptic release properties and expression of key postsynaptic GABA_A receptor subunits are coregulated by hearing.

Evidence of Temporal Cortical Dysfunction in Rhesus Monkeys following Chronic Cocaine Self-Administration

Liu, S., Heitz, R. P., Sampson, A. R., Zhang, W., Bradberry, C. W. — 2008-08-15

Cocaine abusers show impaired performance on cognitive tasks that engage prefrontal cortex. These deficits may contribute to impaired control and relapse in abusers. Understanding the neuronal substrates that lead to these deficits requires animal models that are relevant to the human condition. However, to date, models have mostly focused on behaviors mediated by subcortical systems. Here we evaluated the impact of long-term self-administration of cocaine in the rhesus monkey on cognitive performance. Tests included stimulus discrimination (SD)/reversal and delayed alternation tasks. The chronic cocaine animals showed marked deficits in ability to organize their behavior for maximal reward. This was demonstrated by an increased time needed to acquire SDs. Deficits were also indicated by an increased time to initially learn the delayed alternation task, and to adapt strategies for bypassing a reliance on working memory to respond accurately. Working memory per se (delay dependent performance) was not affected by chronic self-administration. This pattern of cognitive deficits suggests dysfunction that extends beyond localized prefrontal cortical areas. In particular, it appears that temporal cortical function is also compromised. This agrees with other recent clinical and preclinical findings, and suggests further study into addiction related dysfunction across more widespread cortical networks is warranted.

COUP-TFI Coordinates Cortical Patterning, Neurogenesis, and Laminar Fate and Modulates MAPK/ERK, AKT, and ss-Catenin Signaling

2008-08-15

A major unsolved question in cortical development is how proliferation, neurogenesis, regional growth, regional identity, and laminar fate specification are coordinated. Here we provide evidence, using loss-of-function and gain-of-function manipulations, that the COUP-TFI orphan nuclear receptor promotes ventral cortical fate, promotes cell cycle exit and neural differentiation, regulates the balance of early- and late-born neurons, and regulates the balanced production of different types of layer V cortical projection neurons. We suggest that COUP-TFI controls these processes by repressing Mapk/Erk, Akt, and β-catenin signaling.

COMT val158met Genotype Affects Recruitment of Neural Mechanisms Supporting Fluid Intelligence

Bishop, S. J., Fossella, J., Croucher, C. J., Duncan, J. — 2008-08-15

Fluid intelligence (g_f) influences performance across many cognitive domains. It is affected by both genetic and environmental factors. Tasks tapping g_f activate a network of brain regions including the lateral prefrontal cortex (LPFC), the presupplementary motor area/anterior cingulate cortex (pre-SMA/ACC), and the intraparietal sulcus (IPS). In line with the "intermediate phenotype" approach, we assessed effects of a polymorphism (val¹⁵⁸met) in the catechol-O-methyltransferase (COMT) gene on activity within this network and on actual task performance during spatial and verbal g_f tasks. COMT regulates catecholaminergic signaling in prefrontal cortex. The val¹⁵⁸ allele is associated with higher COMT activity than the met¹⁵⁸ allele. Twenty-two volunteers genotyped for the COMT val¹⁵⁸met polymorphism completed high and low g_f versions of spatial and verbal problem-solving tasks. Our results showed a positive effect of COMT val allele load upon the blood oxygen level–dependent response in LPFC, pre-SMA/ACC, and IPS during high g_f versus low g_f task performance in both spatial and verbal domains. These results indicate an influence of the COMT val¹⁵⁸met polymorphism upon the neural circuitry supporting g_f. The behavioral effects of val allele load differed inside and outside the scanner, consistent with contextual modulation of the relation between COMT val¹⁵⁸met genotype and g_f task performance.

Probabilistic Maps, Morphometry, and Variability of Cytoarchitectonic Areas in the Human Superior Parietal Cortex

2008-08-15

Recently, 8 areas (5Ci, 5M, 5L, 7PC, 7A, 7P, 7M, hIP3) in the human superior parietal cortex (SPC) were delineated in 10 postmortem brains using observer-independent cytoarchitectonic analysis. Here we present 3D probabilistic maps of these areas, quantifying the interindividual overlap for each voxel in stereotaxic reference space, and a maximum probability map, providing a contiguous parcellation. For all areas, we determined probabilities of mutual borders, calculated stereotaxic centers of gravity, and estimated volumes. A basic pattern of areas and borders was observed, which showed, however, intersubject variations and a significant interhemispheric asymmetry (7P, 7M) that may be functionally relevant. There was a trend toward higher intersubject anatomical variability in lateral compared with medial areas. For several areas (5M, 7PC, 7A, 7P), variability was significantly higher in the left hemisphere and/or in men, whereas for areas 5Ci and 5M there was a hemisphere-by-gender interaction. Differences in anatomical variability could bias group analyses in functional imaging studies by reducing sensitivity for activations of entities with high variability. The probabilistic maps provide an objective anatomical reference and account for the structural variability of the human brain. Integrated into functional imaging experiments, they can improve structure–function investigations of the human SPC.

Retinotopy and Attention in Human Occipital, Temporal, Parietal, and Frontal Cortex

Saygin, A. P., Sereno, M. I. — 2008-08-15

Novel mapping stimuli composed of biological motion figures were used to study the extent and layout of multiple retinotopic regions in the entire human brain and to examine the independent manipulation of retinotopic responses by visual stimuli and by attention. A number of areas exhibited retinotopic activations, including full or partial visual field representations in occipital cortex, the precuneus, motion-sensitive temporal cortex (extending into the superior temporal sulcus), the intraparietal sulcus, and the vicinity of the frontal eye fields in frontal cortex. Early visual areas showed mainly stimulus-driven retinotopy; parietal and frontal areas were driven primarily by attention; and lateral temporal regions could be driven by both. We found clear spatial specificity of attentional modulation not just in early visual areas but also in classical attentional control areas in parietal and frontal cortex. Indeed, strong spatiotopic activity in these areas could be evoked by directed attention alone. Conversely, motion-sensitive temporal regions, while exhibiting attentional modulation, also responded significantly when attention was directed away from the retinotopic stimuli.

The Effects of Aging on the Neural Correlates of Subjective and Objective Recollection

Duarte, A., Henson, R. N., Graham, K. S. — 2008-08-15

High-functioning older adults can exhibit normal recollection when measured subjectively, via "remember" judgments, but not when measured objectively, via source judgments, whereas low-functioning older adults exhibit impairments for both measures. A potential explanation for this is that typical subjective and objective tests of recollection necessitate different processing demands, supported by distinct brain regions, and that deficits in these tests are observed according to the degree of age-related changes in these regions. Here, we used event-related functional magnetic resonance imaging to measure the effects of aging on neural correlates of subjective and objective measures of recollection, in young, high-functioning (Old-High) and low-functioning (Old-Low) older adults. Behaviorally, the Old-High group showed intact subjective ("remember" judgments) but impaired objective recollection (for 1 of 2 spatial or temporal sources), whereas the Old-Low group was impaired on both measures. Imaging data showed changes in parietal subjective recollection effects in the Old-Low group and in lateral frontal objective recollection effects in both older adult groups. Our results highlight the importance of examining performance variability in older adults and suggest that differential effects of aging on brain regions are associated with different patterns of performance on tests of subjective and objective recollection.

Brain Size and Cortical Structure in the Adult Human Brain

Im, K., Lee, J.-M., Lyttelton, O., Kim, S. H., Evans, A. C., Kim, S. I. — 2008-08-15

We investigated the scale relationship between size and cortical structure of human brains in a large sample of magnetic resonance imaging data. Cortical structure was estimated with several measures (cortical volume, surface area, and thickness, sulcal depth, and absolute mean curvature in sulcal regions and sulcal walls) using three-dimensional surface-based methods in 148 normal subjects (n [men/women]: 83/65, age [mean ± standard deviation]: 25.0 ± 4.9 years). We found significantly larger scaling exponents than geometrically predicted for cortical surface area, absolute mean curvature in sulcal regions and in sulcal walls, and smaller ones for cortical volume and thickness. As brain size increases, the cortex thickens only slightly, but the degree of sulcal convolution increases dramatically, indicating that human cortices are not simply scaled versions of one another. Our results are consistent with previous hypotheses that greater local clustering of interneuronal connections would be required in a larger brain, and fiber tension between local cortical areas would induce cortical folds. We suggest that sex effects are explained by brain size effects in cortical structure at a macroscopic and lobar regional level, and that it is necessary to consider true relationships between cortical measures and brain size due to the limitations of linear stereotaxic normalization.

Dissociation between Explicit Memory and Configural Memory in the Human Medial Temporal Lobe

Preston, A. R., Gabrieli, J. D. E. — 2008-08-15

Using functional magnetic resonance imaging, the current study explored the differential mnemonic contributions of the hippocampus and surrounding medial temporal lobe (MTL) cortices to explicit recognition memory and configural learning. Using a task that required processing of repeated and novel visuospatial contexts across multiple trials, we examined MTL activation in relation to 3 forms of learning in a single paradigm: 1) context-independent procedural learning, 2) context-dependent configural learning, and 3) explicit recognition memory. Activations in hippocampus and parahippocampal cortex were associated with explicit memory, differentiating between subsequently remembered and forgotten repeated contexts, but were unrelated to context-dependent configural learning. Activations in regions of perirhinal and entorhinal cortex were associated with configural learning of repeated contexts independent from explicit memory for those contexts. Procedural learning was unrelated to activation in any MTL region. The time course of activation across learning further differed in MTL subregions with MTL cortex demonstrating repetition-related decreases and hippocampus repetition-related increases. These repetition effects were differentially sensitive to recognition with only activation in hippocampus and parahippocampal cortex tracking recognized items. These imaging findings converge with studies of amnesia and indicate dissociable roles for hippocampus in learning that supports explicit recognition and for anterior MTL cortex in configural learning.

Neurodevelopmental Correlates of True and False Recognition

Paz-Alonso, P. M., Ghetti, S., Donohue, S. E., Goodman, G. S., Bunge, S. A. — 2008-08-15

The Deese/Roediger–McDermott (DRM) false-memory effect has been extensively documented in psychological research. People falsely recognize critical lures or nonstudied items that are semantically associated with studied items. Behavioral research has provided evidence for age-related increases in the DRM false-recognition effect. The present event-related functional magnetic resonance imaging study was aimed at investigating neurodevelopmental changes in brain regions associated with true- and false-memory recognition in 8-year olds, 12-year olds, and adults. Relative to 8-year olds, adults correctly endorsed more studied items as "old" but also mistakenly endorsed more critical lures. Age-related increases in recollection were associated with changes in the medial temporal lobe (MTL) activation profile. Additionally, age-related increases in false alarms (FAs) to semantically related lures were associated with changes in the activation profile of left ventrolateral prefrontal cortex, a region associated with semantic processing. Additional regions exhibiting age-related changes include posterior parietal and anterior prefrontal cortices. In summary, concomitant changes in the MTL, prefrontal cortex, and parietal cortex underlie developmental increases in true and false recognition during childhood and adolescence.

Activation of DOR Attenuates Anoxic K+ Derangement via Inhibition of Na+ Entry in Mouse Cortex

Chao, D., Bazzy-Asaad, A., Balboni, G., Salvadori, S., Xia, Y. — 2008-08-15

We have recently found that in the mouse cortex, activation of -opioid receptor (DOR) attenuates the disruption of K⁺ homeostasis induced by hypoxia or oxygen–glucose deprivation. This novel observation suggests that DOR may protect neurons from hypoxic/ischemic insults via the regulation of K⁺ homeostasis because the disruption of K⁺ homeostasis plays a critical role in neuronal injury under hypoxic/ischemic stress. The present study was performed to explore the ionic mechanism underlying the DOR-induced neuroprotection. Because anoxia causes Na⁺ influx and thus stimulates K⁺ leakage, we investigated whether DOR protects the cortex from anoxic K⁺ derangement by targeting the Na⁺-based K⁺ leakage. By using K⁺-sensitive microelectrodes in mouse cortical slices, we showed that 1) lowering Na⁺ concentration and substituting with impermeable N-methyl-D-glucamine caused a concentration-dependent attenuation of anoxic K⁺ derangement; 2) lowering Na⁺ concentration by substituting with permeable Li⁺ tended to potentiate the anoxic K⁺ derangement; and 3) the DOR-induced protection against the anoxic K⁺ responses was largely abolished by low-Na⁺ perfusion irrespective of the substituted cation. We conclude that external Na⁺ concentration greatly influences anoxic K⁺ derangement and that DOR activation likely attenuates anoxic K⁺ derangement induced by the Na⁺-activated mechanisms in the cortex.