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fMRI activation in a visual-perception task: network of areas detected using the general linear model and independent components analysis.

The Motor-Free Visual Perception Test, revised (MVPT-R), provides a measure of visual perceptual processing. It involves different cognitive elements including visual discrimination, spatial relationships, and mental rotation. We adapted the MVPT-R to an event-related functional MRI (fMRI) environment to investigate the brain regions involved in the interrelation of these cognitive elements. Two complementary analysis methods were employed to characterize the fMRI data: (a) a general linear model SPM approach based upon a model of the time course and a hemodynamic response estimate and (b) independent component analysis (ICA), which does not constrain the specific shape of the time course per se, although we did require it to be at least transiently task-related. Additionally, we implemented ICA in a novel way to create a group average that was compared with the SPM group results. Both methods yielded similar, but not identical, results and detected a network of robustly activated visual, inferior parietal, and frontal eye-field areas as well as thalamus and cerebellum. SPM appeared to be the more sensitive method and has a well-developed theoretical approach to thresholding. The ICA method segregated functional elements into separate maps and identified additional regions with extended activation in response to presented events. The results demonstrate the utility of complementary analyses for fMRI data and suggest that the cerebellum may play a significant role in visual perceptual processing. Additionally, results illustrate functional connectivity between frontal eye fields and prefrontal and parietal regions.

Attention↗

Functional GABAergic synaptic connection in neonatal mouse barrel cortex.

Intracortical inhibition is crucial to proper functioning of the mature neocortex, yet, paradoxically, is reported to be rare or absent in the neonatal animal. We reexamined this issue by recording whole-cell postsynaptic currents (PSCs) of barrel cortex neurons in thalamocortical brain slices from neonatal mice. Monosynaptic, excitatory thalamocortical responses were elicited in layers V/VI neurons as early as postnatal day 0 (P0, the first 24 hr after birth) and in presumptive layer IV as early as P2. At very low stimulation frequencies, the monosynaptic response was invariably followed by a prolonged (up to 1 sec) synaptic barrage, which fatigued at stimulus repetition rates of 2/min or higher. This barrage consisted of postsynaptic responses to spiking activity in neighboring cortical cells, because (1) it could also be evoked by intracortical stimulation in coronal slices and (2) it was abolished by antagonists to NMDA receptors (NMDARs), even when NMDARs on the recorded cell were under a voltage-dependent block. Some of the larger polysynaptic events changed polarity at a negative reversal potential and were blocked by GABAA receptor (GABAAR) antagonists, with a concurrent enhancement of the extracellular field potential, indicating that they were GABAAR- mediated, CI-dependent inhibitory PSCs (IPSCs). We conclude that a network of functional intracortical GABAAR-mediated synaptic connections exists from the earliest postnatal ages, although it gives rise to responses that differ from mature IPSCs in reversal potential and latency.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

Functional neuroanatomy of the hypnotic state.

The neural mechanisms underlying hypnosis and especially the modulation of pain perception by hypnosis remain obscure. Using PET we first described the distribution of regional cerebral blood flow during the hypnotic state. Hypnosis relied on revivification of pleasant autobiographical memories and was compared to imaging autobiographical material in "normal alertness". The hypnotic state was related to the activation of a widespread set of cortical areas involving occipital, parietal, precentral, premotor, and ventrolateral prefrontal and anterior cingulate cortices. This pattern of activation shares some similarities with mental imagery, from which it mainly differs by the relative deactivation of precuneus. Second, we looked at the anti-nociceptive effects of hypnosis. Compared to the resting state, hypnosis reduced pain perception by approximately 50%. The hypnosis-induced reduction of affective and sensory responses to noxious thermal stimulation were modulated by the activity in the midcingulate cortex (area 24a'). Finally, we assessed changes in cerebral functional connectivity related to hypnosis. Compared to normal alertness (i.e., rest and mental imagery), the hypnotic state, significantly enhanced the functional modulation between midcingulate cortex and a large neural network involved in sensory, affective, cognitive and behavioral aspects of nociception. These findings show that not only pharmacological but also psychological strategies for pain control can modulate the cerebral network involved in noxious perception.

Brain↗

Creative innovation: possible brain mechanisms.

This article reviews and develops some theories about the neurobiological basis of creative innovation (CI). CI is defined as the ability to understand and express novel orderly relationships. A high level of general intelligence, domain-specific knowledge and special skills are necessary components of creativity. Specialized knowledge is stored in specific portions of the temporal and parietal lobes. Some anatomic studies suggest that talented people might have alterations of specific regions of the posterior neocortical architecture, but further systematic studies are needed. Intelligence, knowledge and special skills, however, are not sufficient for CI. Developing alternative solutions or divergent thinking has been posited to be a critical element of CI, and clinical as well as functional imaging studies suggest that the frontal lobes are important for these activities. The frontal lobes have strong connections with the polymodal and supramodal regions of the temporal and parietal lobes where concepts and knowledge are stored. These connections might selectively inhibit and activate portions of posterior neocortex and thus be important for developing alternative solutions. Although extensive knowledge and divergent thinking together are critical for creativity they alone are insufficient for allowing a person to find the thread that unites. Finding this thread might require the binding of different forms of knowledge, stored in separate cortical modules that have not been previously associated. Thus, CI might require the co-activation and communication between regions of the brain that ordinarily are not strongly connected. The observations that CI often occurs during levels of low arousal and that many people with depression are creative suggests that alterations of neurotransmitters such as norepinephrine might be important in CI. High levels of norepinephrine, produced by high rates of locus coeruleus firing, restrict the breadth of concept representations and increase the signal to noise ratio, but low levels of norepinephrine shift the brain toward intrinsic neuronal activation with an increase in the size of distributed concept representations and co-activation across modular networks. In addition to being important in divergent thinking, the frontal lobes are also the primary cortical region that controls the locus coeruleus-norepinephrine system. Thus creative people may be endowed with brains that are capable of storing extensive specialized knowledge in their temporoparietal cortex, be capable of frontal mediated divergent thinking and have a special ability to modulate the frontal lobe-locus coeruleus (norepinephrine) system, such that during creative innovation cerebral levels of norepinephrine diminish, leading to the discovery of novel orderly relationships.

Animals↗

Cortical orofacial motor representation in Old World monkeys, great apes, and humans. II. Stereologic analysis of chemoarchitecture.

This study presents a comparative stereologic investigation of neurofilament protein- and calcium-binding protein-immunoreactive neurons within the region of orofacial representation of primary motor cortex (Brodmann's area 4) in several catarrhine primate species (Macaca fascicularis, Papio anubis, Pongo pygmaeus, Gorilla gorilla, Pan troglodytes, and Homo sapiens). Results showed that the density of interneurons involved in vertical interlaminar processing (i.e., calbindin- and calretinin-immunoreactive neurons) as well pyramidal neurons that supply heavily-myelinated projections (i.e., neurofilament protein-immunoreactive neurons) are correlated with overall neuronal density, whereas interneurons making transcolumnar connections (i.e., parvalbumin-immunoreactive neurons) do not exhibit such a relationship. These results suggest that differential scaling rules apply to different neuronal subtypes depending on their functional role in cortical circuitry. For example, cortical columns across catarrhine species appear to involve a similar conserved network of intracolumnar inhibitory interconnections, as represented by the distribution of calbindin- and calretinin-immunoreactive neurons. The subpopulation of horizontally-oriented wide-arbor interneurons, on the other hand, increases in density relative to other interneuron subpopulations in large brains. Due to these scaling trends, the region of orofacial representation of primary motor cortex in great apes and humans is characterized by a greater proportion of neurons enriched in neurofilament protein and parvalbumin compared to the Old World monkeys examined. These modifications might contribute to the voluntary dexterous control of orofacial muscles in great ape and human communication.

Animal Communication↗

Signal propagation and logic gating in networks of integrate-and-fire neurons.

Transmission of signals within the brain is essential for cognitive function, but it is not clear how neural circuits support reliable and accurate signal propagation over a sufficiently large dynamic range. Two modes of propagation have been studied: synfire chains, in which synchronous activity travels through feedforward layers of a neuronal network, and the propagation of fluctuations in firing rate across these layers. In both cases, a sufficient amount of noise, which was added to previous models from an external source, had to be included to support stable propagation. Sparse, randomly connected networks of spiking model neurons can generate chaotic patterns of activity. We investigate whether this activity, which is a more realistic noise source, is sufficient to allow for signal transmission. We find that, for rate-coded signals but not for synfire chains, such networks support robust and accurate signal reproduction through up to six layers if appropriate adjustments are made in synaptic strengths. We investigate the factors affecting transmission and show that multiple signals can propagate simultaneously along different pathways. Using this feature, we show how different types of logic gates can arise within the architecture of the random network through the strengthening of specific synapses.

Action Potentials↗

On the function of dendritic spines.

Dendritic spines occupy a strategic position in the central nervous system, yet their function is still under debate. Over the past decades, many hypotheses have been put forward to explain the specific function of spines. Recently, imaging experiments have demonstrated that spines compartmentalize calcium, a role that appears necessary for input-specific forms of synaptic plasticity. In addition, it has been discovered that spine morphology is plastic over fast time scales and can be controlled by specific biochemical pathways. Also, several aspects of the spine's morphology appear to be intricately linked to its function. The authors review these recent data and incorporate them into a model for the function of dendritic spines in CNS circuits. In their proposal, spines serve to specifically connect sparse inputs and therefore minimize the wiring necessary in the CNS while maximizing connectivity. By virtue of the same design, spines isolate inputs and thus implement local learning rules. These rules appear only necessary with sparse inputs so these two functions are intimately related. Spines therefore would play a crucial circuit role, remarkably analogous to synaptic matrix elements of associative neural networks. This model highlights the economical, yet elegant, design of CNS circuits.

Animals↗

Characteristic functional networks in high- versus low-proficiency second language speakers detected also during native language processing: an explorative EEG coherence study in 6 frequency bands.

An EEG coherence study was performed with a twofold objective: first, to scrutinize the theoretical concept of "cortical efficiency" in connection with second language (L2) acquisition and, second, to detect cooperations between cortical areas in specific frequency bands indicative for highly proficient L2 processing. Two groups differing only in their level of L2 proficiency were contrasted during presentation of natural language videos in English (L2) and German (native language, L1), with explorative coherence analysis in 6 frequency bands (0.5-31.5 Hz). The coherence brain maps revealed more pronounced and widespread increases in coherences in the alpha1-band (8-10 Hz) in low-proficiency than in the high-proficiency L2 speakers. Surprisingly, this difference was obtained also during L1 processing and corroborated for both languages by multivariate permutation tests. These tests revealed additional differences between the low- and the high-proficiency group also for coherences within the beta1- (13-18 Hz) and the beta2-band (18.5-31.5 Hz), again during L2 and L1 processing. Since the same group differences were observed during L1 and L2 processing, our high-proficiency group might have profited from a more generic advantage in language or text processing strategy. This strategic advantage was most evident at alpha1 frequencies, possibly related to a specific way of processing internal mental states (top-down processing).

Acoustic Stimulation↗

Differential modulation of subcortical target and cortex during deep brain stimulation.

The combination of electrical deep brain stimulation (DBS) with functional imaging offers a unique model for tracing brain circuitry and for testing the modulatory potential of electrical stimulation on a neuronal network in vivo. We therefore applied parametric positron emission tomography (PET) analyses that allow characterization of rCBF responses as linear and nonlinear functions of the experimentally modulated stimulus (variable stimulator setting). In patients with electrodes in the thalamic ventrointermediate nucleus (VIM) for the treatment of essential tremor (ET) here we show that variations in voltage and frequency of thalamic stimulation have differential effects in a thalamo-cortical circuitry. Increasing stimulation amplitude was associated with a linear raise in rCBF at the thalamic stimulation site, but with a nonlinear rCBF response in the primary sensorimotor cortex (M1/S1). The reverse pattern in rCBF changes was observed with increasing stimulation frequency. These results indicate close connectivity between the stimulated nucleus (VIM) and primary sensorimotor cortex. Likewise, stimulation parameter-specific modulation occurs at this simple interface between an electrical and a cerebral system and suggests that the scope of DBS extends beyond an ablation-like on-off effect: DBS could rather allow a gradual tuning of activity within a neuronal circuit.

Aged↗

Analysis of information transmission in the Schaffer collaterals.

Hippocampal region CA1 seems from comparative studies to be particularly important in the primate brain, in addition to being crucial to memory function. Thus, it is an extremely appropriate place to begin a quantitative investigation of the information representation and transmission capabilities of cerebral neural networks. In this study, a mathematical model of the Schaffer collateral projection from CA3 to CA1 is described. From the model, the amount of information that can be conveyed by the Schaffer collaterals is calculated, i.e., the information that a pattern of firing in CA1 conveys about a pattern of firing in CA3, because of the connections between them. The calculation is performed analytically for an arbitrary probability distribution describing the pattern of CA3 firing and then solved numerically for particular input distributions. The effect of a number of issues on the information conveyed is examined. Consideration of the effect of the amount of analog resolution of firing rates in the patterns of activity in CA3 confirmed information transmission to be most efficient for binary codes, to a degree that depends on the sparseness of activity. For very sparse codes, a binary code allows more information to be received even in absolute terms, but for more distributed codes, slightly more information can be received by CA1 by making use of analog resolution. The pattern of convergence of connections from CA3 to CA1 is examined, i.e., the spatial distribution of the number of connections each CA1 neuron receives. It is found that the effect of the difference between a uniform convergence model and a proposed real convergence pattern (Bernard and Wheal, Hippocampus 1994;4:497-529) is minimal. The effect of the ratio of expansion between CA3 and CA1 due to the relative numbers of neurons in these two areas is studied. The Schaffer collaterals in all mammalian species reported in the literature seem to operate in a regime in which there is at least the scope for efficient transfer of information. In addition, the effect of topography (with respect to the transverse hippocampal axis) in the Schaffer collateral connectivity is examined. In the absence of spatial correlations, topography is found to have essentially no effect on information transmission. If spatial correlations in firing were present in CA3 (which, however, would be less efficient for memory storage in the recurrent collaterals), information transmission would be maximized by matching the topographic spread to the spatial scale of correlation.

Animals↗

Brain-derived neurotrophic factor controls functional differentiation and microcircuit formation of selectively isolated fast-spiking GABAergic interneurons.

GABAergic interneurons with high-frequency firing, fast-spiking (FS) cells, form synapses on perisomatic regions of principal cells in the neocortex and hippocampus to control the excitability of cortical networks. Brain-derived neurotrophic factor (BDNF) is essential for the differentiation of multiple interneuron subtypes and the formation of their synaptic contacts. Here, we examined whether BDNF, alone or in conjunction with sustained KCl-induced depolarization, drives functional FS cell differentiation and the formation of inhibitory microcircuits. Homogeneous FS cell cultures were established by target-specific isolation using the voltage-gated potassium channel 3.1b subunit as the selection marker. Isolated FS cells expressed parvalbumin, were surrounded by perineuronal nets, formed immature inhibitory connections and generated slow action potentials at 12 days in vitro. Brain-derived neurotrophic factor (BDNF) promoted FS cell differentiation by increasing the somatic diameter, dendritic branching and the frequency of action potential firing. In addition, BDNF treatment led to a significant up-regulation of synaptophysin and vesicular GABA transporter expression, components of the synaptic machinery critical for GABA release, which was paralleled by an increase in synaptic strength. Long-term membrane depolarization alone was detrimental to dendritic branching. However, we observed that BDNF and KCl exerted additive effects, as reflected by the significantly accelerated maturation of synaptic contacts and high discharge frequencies, and was required for the formation of reciprocal connections between FS cells. Our results show that BDNF, along with membrane depolarization, is critical for FS cells to establish inhibitory circuitries during corticogenesis.

Action Potentials↗

Cognitive map formation through sequence encoding by theta phase precession.

The rodent hippocampus has been thought to represent the spatial environment as a cognitive map. The associative connections in the hippocampus imply that a neural entity represents the map as a geometrical network of hippocampal cells in terms of a chart. According to recent experimental observations, the cells fire successively relative to the theta oscillation of the local field potential, called theta phase precession, when the animal is running. This observation suggests the learning of temporal sequences with asymmetric connections in the hippocampus, but it also gives rather inconsistent implications on the formation of the chart that should consist of symmetric connections for space coding. In this study, we hypothesize that the chart is generated with theta phase coding through the integration of asymmetric connections. Our computer experiments use a hippocampal network model to demonstrate that a geometrical network is formed through running experiences in a few minutes. Asymmetric connections are found to remain and distribute heterogeneously in the network. The obtained network exhibits the spatial localization of activities at each instance as the chart does and their propagation that represents behavioral motions with multidirectional properties. We conclude that theta phase precession and the Hebbian rule with a time delay can provide the neural principles for learning the cognitive map.

Algorithms↗

Effects of healthy aging on hippocampal and rhinal memory functions: an event-related fMRI study.

Event-related functional magnetic resonance imaging was used to study the effects of healthy aging on hippocampal and rhinal memory functions. Memory for past events can be based on retrieval accompanied by specific contextual details (recollection) or on the feeling that an event is old or new without the recovery of contextual details (familiarity). There is evidence that recollection is more dependent on hippocampus, whereas familiarity is more dependent on the rhinal cortex, and that healthy aging has greater effects on recollection than on familiarity. However, little evidence is available about the neural correlates of these effects. Here, we isolated activity associated with recollection and familiarity by distinguishing between linear and quasi-exponential "perceived oldness" functions derived from recognition confidence levels. The main finding was a double dissociation within the medial temporal lobes between recollection-related activity in hippocampus, which was reduced by aging, and familiarity-related activity in rhinal cortex, which was increased by aging. In addition, age dissociations were found within parietal and posterior midline regions. Finally, aging reduced functional connectivity within a hippocampal-retrosplenial/parietotemporal network but increased connectivity within a rhinal-frontal network. These findings indicate that older adults compensate for hippocampal deficits by relying more on rhinal cortex, possibly through a top-down frontal modulation. This finding has important clinical implications because early Alzheimer's disease impairs both hippocampus and rhinal cortex.

Adult↗

Human anterior and frontal midline theta and lower alpha reflect emotionally positive state and internalized attention: high-resolution EEG investigation of meditation.

EEG spectral power and coherence estimates in the individually defined delta, theta, alpha-1, alpha-2, and alpha-3 bands were used to identify and characterize brain regions involved in meditative states, in which focused internalized attention gives rise to emotionally positive "blissful" experience. Blissful state was accompanied by increased anterior frontal and midline theta synchronization as well as enhanced theta long-distant connectivity between prefrontal and posterior association cortex with distinct "center of gravity" in the left prefrontal region (AF3 site). Subjective scores of emotional experience significantly correlated with theta, whereas scores of internalized attention with both theta and alpha lower synchronization. Our results propose selective associations of theta and alpha oscillating networks activity with states of internalized attention and positive emotional experience.

Adult↗

Discrimination between demented patients and normals based on topographic EEG slow wave activity: comparison between z statistics, discriminant analysis and artificial neural network classifiers.

The topographic distributions of absolute delta and theta powers were used to classify demented patients and normals by means of z statistics, discriminant analysis and artificial neural networks (NN). The data were taken from two psychopharmacological studies in mildly to moderately demented patients (111 and 96 patients for studies I and II, respectively) and from 56 normal healthy controls. All patients were diagnosed according to DSM-III criteria and were free of medication for at least 2 weeks. The NN used was a strictly layered feed-forward network with complete connections. The z-transformed absolute power values in the combined delta and theta frequency range at 17 electrodes, recorded in a 3 min vigilance-controlled EEG with eyes closed, were used as input. After having trained the NN successfully by backpropagating of errors, the generalization test with independent data results in a classification performance of 90% determined by "relative operating characteristic" analysis. The NN out-performed z statistics and discriminant analysis. This high percentage of correct classifications may justify the development of further application of NNs based on topographic EEG data.

Aged↗

Intrahippocampal connections in the pigeon (Columba livia) as revealed by stimulation evoked field potentials.

The hippocampal formation (HF) of mammals and birds is crucial for spatial learning and memory. However, although the underlying synaptic organization and connectivity of the mammalian HF are well characterized, comparatively little is known about the avian HF. Localized regions of the homing pigeon HF were stimulated at 400-600 microA while evoked field potentials (EFPs) were recorded from adjacent and more distant HF areas relative to the stimulation site. The shortest discernible EFP latency was 12.2 msec. The emerging connectivity profile (using the location of peak EFP amplitude after stimulation and making no determination of the number of intervening synapses) was characterized by projections from the dorsolateral (DL) HF to the dorsomedial (DM) HF (15-msec latency) at the same anterior/posterior (A/P) level, DM to ventrolateral (VL) and ventromedial (VM; 15 msec) HF across A/P levels, VM to VL (12 msec) and contralateral VM (15 msec) at the same A/P level, and VL to ventral DL (DLv; 15 msec) across A/P levels posterior to the stimulation site. Using these data as a first approximation, connectivity through the avian HF appears to be characterized by a discernible feed-forward network starting with a projection from DL to DM, DM to VL, VM, and contralateral VM, VM to VL, and VL to posterior ventral DLv. Although still speculative, the results suggest that the internal connectivity of the avian HF is similar to that of the mammalian HF, despite the large evolutionary divergence between the two taxa.

Animals↗

Prefrontal and executive attention network lesions and the development of attention-deficit/hyperactivity symptomatology.

OBJECTIVE: To investigate the association between focal stroke lesions of Posner's executive attention network and a specific region of interest in the frontal lobes (orbital frontal and mesial frontal) and either attention-deficit/hyperactivity disorder (ADHD) or traits of the disorder (ADHD symptomatology). METHOD: Twenty-nine children with focal stroke lesions were studied with standardized psychiatric assessments and anatomical brain magnetic resonance imaging. The pattern of lesion overlap in subjects with ADHD symptomatology was determined. RESULTS: Fifteen of 28 subjects with no prestroke ADHD were diagnosed with ADHD symptomatology at the time of assessment. The extent of lesions within the executive attention network was marginally related to ADHD symptomatology (p = .088; effect size = 0.66), whereas the extent of lesions in the specific frontal region of interest was significantly related to ADHD symptomatology (p = .040; effect size = 0.82). CONCLUSIONS: Lesions within Posner's executive attention network and its orbital frontal connections may be linked to important mechanisms in the expression of ADHD symptomatology after childhood stroke. These findings are consistent with functional and structural imaging findings in studies of idiopathic ADHD.

Attention Deficit Disorder with Hyperactivity↗

[Changes in synaptic potentials and axonal delays as factors causing epileptic instability of neuronal networks].

Synaptic weights, axonal delays and excitability thresholds are three basic parameters influencing the function of neuronal network as a dynamic system. Changes of the general level of the signal flow, without changes in relation between excitatory and inhibitory connections can cause pathologic oscillations in the network. The conductivity in neuronal nets depends on electrochemical processes and may be influenced by the pH-status, ion concentrations, among other parameters. Also different pathological processes can change it. Even slight changes of axonal delays, as shown above, can cause in certain situations unstable, epileptic oscillations of the net.

Action Potentials↗