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Traumatic brain injury (TBI) is characterized by acute neurological dysfunction and associated with the development of chronic traumatic encephalopathy (CTE) and Alzheimer's disease. We previously showed that cis phosphorylated tau (cis P-tau), but not the trans form, contributes to tau pathology and functional impairment in an animal model of severe TBI. Here we found that in human samples obtained post TBI due to a variety of causes, cis P-tau is induced in cortical axons and cerebrospinal fluid and positively correlates with axonal injury and clinical outcome. Using mouse models of severe or repetitive TBI, we showed that cis P-tau elimination with a specific neutralizing antibody administered immediately or at delayed time points after injury, attenuates the development of neuropathology and brain dysfunction during acute and chronic phases including CTE-like pathology and dysfunction after repetitive TBI. Thus, cis P-tau contributes to short-term and long-term sequelae after TBI, but is effectively neutralized by cis antibody treatment.Induction of the cis form of phosphorylated tau (cis P-tau) has previously been shown to occur in animal models of traumatic brain injury (TBI), and blocking this form of tau using antibody was beneficial in a rodent model of severe TBI. Here the authors show that cis P-tau induction is a feature of several different forms of TBI in humans, and that administration of cis P-tau targeting antibody to rodents reduces or delays pathological features of TBI.

Understanding how the brain extracts and combines temporal structure (rhythm) information from events presented to different senses remains unresolved. Many neuroimaging beat perception studies have focused on the auditory domain and show the presence of a highly regular beat (isochrony) in "auditory" stimulus streams enhances neural responses in a distributed brain network and affects perceptual performance. Here, we acquired functional magnetic resonance imaging (fMRI) measurements of brain activity while healthy human participants performed a visual task on isochronous versus randomly timed "visual" streams, with or without concurrent task-irrelevant sounds. We found that visual detection of higher intensity oddball targets was better for isochronous than randomly timed streams, extending previous auditory findings to vision. The impact of isochrony on visual target sensitivity correlated positively with fMRI signal changes not only in visual cortex but also in auditory sensory cortex during audiovisual presentations. Visual isochrony activated a similar timing-related brain network to that previously found primarily in auditory beat perception work. Finally, activity in multisensory left posterior superior temporal sulcus increased specifically during concurrent isochronous audiovisual presentations. These results indicate that regular isochronous timing can modulate visual processing and this can also involve multisensory audiovisual brain mechanisms.

The brain seeks to combine related inputs from different senses (e.g., hearing and vision), via multisensory integration. Temporal information can indicate whether stimuli in different senses are related or not. A recent human fMRI study (Noesselt et al. [2007]: J Neurosci 27:11431-11441) used auditory and visual trains of beeps and flashes with erratic timing, manipulating whether auditory and visual trains were synchronous or unrelated in temporal pattern. A region of superior temporal sulcus (STS) showed higher BOLD signal for the synchronous condition. But this could not be related to performance, and it remained unclear if the erratic, unpredictable nature of the stimulus trains was important. Here we compared synchronous audiovisual trains to asynchronous trains, while using a behavioral task requiring detection of higher-intensity target events in either modality. We further varied whether the stimulus trains had predictable temporal pattern or not. Synchrony (versus lag) between auditory and visual trains enhanced behavioral sensitivity (d') to intensity targets in either modality, regardless of predictable versus unpredictable patterning. The analogous contrast in fMRI revealed BOLD increases in several brain areas, including the left STS region reported by Noesselt et al. [2007: J Neurosci 27:11431-11441]. The synchrony effect on BOLD here correlated with the subject-by-subject impact on performance. Predictability of temporal pattern did not affect target detection performance or STS activity, but did lead to an interaction with audiovisual synchrony for BOLD in inferior parietal cortex., (Copyright © 2011 Wiley-Liss, Inc.)

Cognitive processes such as visual perception and selective attention induce specific patterns of brain oscillations. The neurochemical bases of these spectral changes in neural activity are largely unknown, but neuromodulators are thought to regulate processing. The cholinergic system is linked to attentional function in vivo, whereas separate in vitro studies show that cholinergic agonists induce high-frequency oscillations in slice preparations. This has led to theoretical proposals that cholinergic enhancement of visual attention might operate via gamma oscillations in visual cortex, although low-frequency alpha/beta modulation may also play a key role. Here we used MEG to record cortical oscillations in the context of administration of a cholinergic agonist (physostigmine) during a spatial visual attention task in humans. This cholinergic agonist enhanced spatial attention effects on low-frequency alpha/beta oscillations in visual cortex, an effect correlating with a drug-induced speeding of performance. By contrast, the cholinergic agonist did not alter high-frequency gamma oscillations in visual cortex. Thus, our findings show that cholinergic neuromodulation enhances attentional selection via an impact on oscillatory synchrony in visual cortex, for low rather than high frequencies. We discuss this dissociation between high- and low-frequency oscillations in relation to proposals that lower-frequency oscillations are generated by feedback pathways within visual cortex., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Although oscillatory activity in the alpha band was traditionally associated with lack of alertness, more recent work has linked it to specific cognitive functions, including visual attention. The emerging method of rhythmic transcranial magnetic stimulation (TMS) allows causal interventional tests for the online impact on performance of TMS administered in short bursts at a particular frequency. TMS bursts at 10 Hz have recently been shown to have an impact on spatial visual attention, but any role in featural attention remains unclear. Here we used rhythmic TMS at 10 Hz to assess the impact on attending to global or local components of a hierarchical Navon-like stimulus (D. Navon (1977) Forest before trees: The precedence of global features in visual perception. Cognit. Psychol., 9, 353), in a paradigm recently used with TMS at other frequencies (V. Romei, J. Driver, P.G. Schyns & G. Thut. (2011) Rhythmic TMS over parietal cortex links distinct brain frequencies to global versus local visual processing. Curr. Biol., 2, 334-337). In separate groups, left or right posterior parietal sites were stimulated at 10 Hz just before presentation of the hierarchical stimulus. Participants had to identify either the local or global component in separate blocks. Right parietal 10 Hz stimulation (vs. sham) significantly impaired global processing without affecting local processing, while left parietal 10 Hz stimulation vs. sham impaired local processing with a minor trend to enhance global processing. These 10 Hz outcomes differed significantly from stimulation at other frequencies (i.e. 5 or 20 Hz) over the same site in other recent work with the same paradigm. These dissociations confirm differential roles of the two hemispheres in local vs. global processing, and reveal a frequency-specific role for stimulation in the alpha band for regulating feature-based visual attention., (© 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.)

Cognitive processes, such as spatial attention, are thought to rely on extended networks in the human brain. Both clinical data from lesioned patients and fMRI data acquired when healthy subjects perform particular cognitive tasks typically implicate a wide expanse of potentially contributing areas, rather than just a single brain area. Conversely, evidence from more targeted interventions, such as transcranial magnetic stimulation (TMS) or invasive microstimulation of the brain, or selective study of patients with highly focal brain damage, can sometimes indicate that a single brain area may make a key contribution to a particular cognitive process. But this in turn raises questions about how such a brain area may interface with other interconnected areas within a more extended network to support cognitive processes. Here, we provide a brief overview of new approaches that seek to characterise the causal role of particular brain areas within networks of several interacting areas, by measuring the effects of manipulations for a targeted area on function in remote interconnected areas. In human participants, these approaches include concurrent TMS-fMRI and TMS-EEG, as well as combination of the focal lesion method in selected patients with fMRI and/or EEG measures of the functional impact from the lesion on interconnected intact brain areas. Such approaches shed new light on how frontal cortex and parietal cortex modulate sensory areas in the service of attention and cognition, for the normal and damaged human brain.

We used functional magnetic resonance imaging (fMRI) to investigate the brain basis of overt and covert forms of attention during search, while employing stringent control of both eye movements and attentional shifts. A factorial design compared overt and covert forms of goal-directed serial search versus stimulus-driven tracking. To match ocular changes and the number and magnitude of attention shifts across cells in the design, stimulus-driven tracking involved trial-specific "replay" of previous goal-directed eye movements. We found that, in terms of cortical activations, engagement of the dorsal fronto-parietal network by goal-directed attention did not depend on oculomotor requirements, being found similarly for covert attention, in accord with other work. However, analyses of effective connectivity (or "functional coupling") revealed that information flow within this network changed significantly as a function of both the task (goal-directed or stimulus-driven) and the overt versus covert form of attention. Additionally, we observed a distinct set of subcortical regions (pulvinar and caudate nucleus) engaged primarily during the covert form of goal-directed search. We conclude that dynamics within the dorsal fronto-parietal attentional system flexibly reorganize to integrate task demands and oculomotor requirements.

Neuroimaging can address activity across the entire brain in relation to cognition, but is typically correlative rather than causal. Brain stimulation can target a local brain area causally, but without revealing the entire network affected. Combining brain stimulation with concurrent neuroimaging allows a new causal approach to how interplay between extended networks of brain regions can support cognition. Brain stimulation does not affect only the targeted local region but also activity in remote interconnected regions. These remote effects depend on cognitive factors (e.g. task-condition), revealing dynamic changes in interplay between brain areas. We illustrate this with examples from top-down modulation of visual cortex, response-competition, inter-hemispheric rivalry and motor tasks; but the new approach should be applicable to many domains of cognition.

Purpose: To characterize and eliminate a new type of image artifact in concurrent transcranial magnetic stimulation and functional MRI (TMS-fMRI) caused by small leakage currents originating from the high-voltage capacitors in the TMS stimulator system., Materials and Methods: The artifacts in echo-planar images (EPI) caused by leakage currents were characterized and quantified in numerical simulations and phantom studies with different phantom-coil geometries. A relay-diode combination was devised and inserted in the TMS circuit that shorts the leakage current. Its effectiveness for artifact reduction was assessed in a phantom scan resembling a realistic TMS-fMRI experiment., Results: The leakage-current-induced signal changes exhibited a multipolar spatial pattern and the maxima exceeded 1% at realistic coil-cortex distances. The relay-diode combination effectively reduced the artifact to a negligible level., Conclusion: The leakage-current artifacts potentially obscure effects of interest or lead to false-positives. Since the artifact depends on the experimental setup and design (eg, amplitude of the leakage current, coil orientation, paradigm, EPI parameters), we recommend its assessment for each experiment. The relay-diode combination can eliminate the artifacts if necessary.

Transcranial magnetic stimulation (TMS) produces a direct causal effect on brain activity that can now be studied by new approaches that simultaneously combine TMS with neuroimaging methods, such as functional magnetic resonance imaging (fMRI). In this review we highlight recent concurrent TMS-fMRI studies that illustrate how this novel combined technique may provide unique insights into causal interactions among brain regions in humans. We show how fMRI can detect the spatial topography of local and remote TMS effects and how these may vary with psychological factors such as task-state. Concurrent TMS-fMRI may furthermore reveal how the brain adapts to so-called virtual lesions induced by TMS, and the distributed activity changes that may underlie the behavioural consequences often observed during cortical stimulation with TMS. We argue that combining TMS with neuroimaging techniques allows a further step in understanding the physiological underpinnings of TMS, as well as the neural correlated of TMS-evoked consequences on perception and behaviour. This can provide powerful new insights about causal interactions among brain regions in both health and disease that may ultimately lead to developing more efficient protocols for basic research and therapeutic TMS applications.

To investigate whether saccade preparation can modulate processing of auditory stimuli in a spatially-specific fashion, ERPs were recorded for a Saccade task, in which the direction of a prepared saccade was cued, prior to an imperative auditory stimulus indicating whether to execute or withhold that saccade. For comparison, we also ran a conventional Covert Attention task, where the same cue now indicated the direction for a covert endogenous attentional shift prior to an auditory target-nontarget discrimination. Lateralised components previously observed during cued shifts of attention (ADAN, LDAP) did not differ significantly across tasks, indicating commonalities between auditory spatial attention and oculomotor control. Moreover, in both tasks, spatially-specific modulation of auditory processing was subsequently found, with enhanced negativity for lateral auditory nontarget stimuli at cued versus uncued locations. This modulation started earlier and was more pronounced for the Covert Attention task, but was also reliably present in the Saccade task, demonstrating that the effects of covert saccade preparation on auditory processing can be similar to effects of endogenous covert attentional orienting, albeit smaller. These findings provide new evidence for similarities but also some differences between oculomotor preparation and shifts of endogenous spatial attention. They also show that saccade preparation can affect not just vision, but also sensory processing of auditory events.

Although much traditional sensory research has studied each sensory modality in isolation, there has been a recent explosion of interest in causal interplay between different senses. Various techniques have now identified numerous multisensory convergence zones in the brain. Some convergence may arise surprisingly close to low-level sensory-specific cortex, and some direct connections may exist even between primary sensory cortices. A variety of multisensory phenomena have now been reported in which sensory-specific brain responses and perceptual judgments concerning one sense can be affected by relations with other senses. We survey recent progress in this multisensory field, foregrounding human studies against the background of invasive animal work and highlighting possible underlying mechanisms. These include rapid feedforward integration, possible thalamic influences, and/or feedback from multisensory regions to sensory-specific brain areas. Multisensory interplay is more prevalent than classic modular approaches assumed, and new methods are now available to determine the underlying circuits.

We compared the contribution of featural information and second-order spatial relations (spacing between features) in face processing. A fully factorial design has the same or different "features" (eyes, mouth, and nose) across two successive displays, whereas, orthogonally, the second-order spatial relations between those features were the same or different. The range of such changes matched the possibilities within the population of natural face images. Behaviorally, we found that judging whether two successive faces depicted the same person was dominated by features, although second-order spatial relations also contributed. This influence of spatial relations correlated, for individual subjects, with their skill at recognition of faces (as famous, or as previously exposed) in separate behavioral tests. Using the same repetition design in functional magnetic resonance imaging, we found feature-dependent effects in the lateral occipital and right fusiform regions. In addition, there were spatial relation effects in the bilateral inferior occipital gyrus and right fusiform that correlated with individual differences in (separately measured) behavioral sensitivity to those changes. The results suggest that featural and second-order spatial relation aspects of faces make distinct contributions to behavioral discrimination and recognition, with features contributing most to face discrimination and second-order spatial relational aspects correlating best with recognition skills. Distinct neural responses to these aspects were found with functional magnetic resonance imaging, particularly when individual skills were taken into account for the impact of second-order spatial relations.

Visual processing is not determined solely by retinal inputs. Attentional modulation can arise when the internal attentional state (current task) of the observer alters visual processing of the same stimuli. This can influence visual cortex, boosting neural responses to an attended stimulus. Emotional modulation can also arise, when affective properties (emotional significance) of stimuli, rather than their strictly visual properties, influence processing. This too can boost responses in visual cortex, as for fear-associated stimuli. Both attentional and emotional modulation of visual processing may reflect distant influences upon visual cortex, exerted by brain structures outside the visual system per se. Hence, these modulations may provide windows onto causal interactions between distant but interconnected brain regions. We review recent evidence, noting both similarities and differences between attentional and emotional modulation. Both can affect visual cortex, but can reflect influences from different regions, such as fronto-parietal circuits versus the amygdala. Recent work on this has developed new approaches for studying causal influences between human brain regions that may be useful in other cognitive domains. The new methods include application of functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) measures in brain-damaged patients to study distant functional impacts of their focal lesions, and use of transcranial magnetic stimulation concurrently with fMRI or EEG in the normal brain. Cognitive neuroscience is now moving beyond considering the putative functions of particular brain regions, as if each operated in isolation, to consider, instead, how distinct brain regions (such as visual cortex, parietal or frontal regions, or amygdala) may mutually influence each other in a causal manner.

Incoming signals from different sensory modalities are initially processed in separate brain regions. But because these different signals can arise from common events or objects in the external world, integration between them can be useful. Such integration is subject to spatial and temporal constraints, presumably because a common source is more likely for information arising from around the same place and time. This review focuses on recent neuroimaging data concerning spatial aspects of multisensory integration in the human brain. These findings indicate not only that multisensory integration involves anatomical convergence from sensory-specific ('unimodal') cortices into multisensory ('heteromodal') brain areas, but also that multisensory spatial interactions can affect even so-called 'unimodal' brain regions. Such findings call for a revision of traditional assumptions about multisensory processing in the brain.

How the brain represents different aspects of faces remains controversial. Here we presented subjects with stimuli drawn from morph continua between pairs of famous faces. In the paired presentations, a second face could be identical to the first, could share perceived identity but differ physically (30% along the morph continuum), or could differ physically by the same distance along the continuum (30%) but in the other direction. We show that, behaviorally, subjects are more likely to classify face pairs in the third paired presentation as different and that this effect is more pronounced for subjects who are more familiar with the faces. In functional magnetic resonance imaging (fMRI), inferior occipital gyrus (IOG) shows sensitivity to physical rather than to identity changes, whereas right fusiform gyrus (FFG) shows sensitivity to identity rather than to physical changes. Bilateral anterior temporal regions show sensitivity to identity change that varies with the subjects' pre-experimental familiarity with the faces. These findings provide neurobiological support for a hierarchical model of face perception.

We used positron emission tomography (PET) to investigate the neural correlates of selective attention in humans. We examined the effects of attending to one side of space versus another (spatial selection) and to one sensory modality versus another (intermodal selection) during bilateral, bimodal stimulation of vision and touch. Attention toward one side resulted in greater activity in several contralateral areas. In somatosensory cortex, these spatial attentional modulations were found only when touch was relevant. In the intraparietal sulcus, spatial attentional effects were multimodal, independent of the modality attended. In occipital areas, spatial modulations were also found during both visual and tactile attention, indicating that tactile attention can affect activity in visual cortex; but occipital areas also showed more activity overall during visual attention. This suggests that while spatial attention can exert multimodal influences on visual areas, these still maintain their specificity for the visual modality. Additionally, irrespective of the attended side, attending to vision activated posterior parietal and superior premotor cortices, while attending to touch activated the parietal operculi. We conclude that attentional selection operates at multiple levels, with attention to locations and attention to modalities showing distinct effects. These jointly contribute to boost processing of stimuli at the attended location in the relevant modality.

Several recent studies have shown cross-modal visual-tactile extinction in patients with right hemisphere lesions. In the present case, patient BV, a visual stimulus close to the right hand extinguished awareness of a touch on the left hand that would otherwise have been felt. Such extinction was reduced if the right visual stimulus was placed more distant from the patient's hand in the radial plane. However, when the patient held sticks in both hands, so that a far right visual stimulus was now at the end of the "tool" in his right hand, cross-modal extinction from this far stimulus increased. This effect depended on the patient holding a stick that reached to the position of the far visual stimulus; a similar large stick, but not connected with the patient's hand and laying passively on the right, had no effect. Wielding the stick induced a re-mapping of space, so that the far light became treated as near (and reachable by) the hand, thus modifying the spatial nature of cross-modal extinction. This may relate to the properties of multimodal neurons as found in the monkey intraparietal sulcus.

In the present paper, we review several functional imaging studies investigating crossmodal interactions between vision and touch relating to spatial attention. We asked how the spatial unity of a multimodal event in the external world might be represented in the brain, where signals from different modalities are initially processed in distinct brain regions. The results highlight several links between visual and tactile spatial representations. First, we found that activity in the anterior part of the intraparietal sulcus was influenced by stimulus position independently of the modality of the stimulation. This is consistent with crossmodal interactions via sensory convergence from early modality-specific spatial maps to higher-order multimodal regions. Second, we found that stimulation in, or attention to, one modality could affect activity in areas dedicated to a different modality, in a spatially-specific manner. These spatial crossmodal effects in unimodal regions demonstrate congruous activity in anatomically distant brain areas that represent similar external locations, implicating a distributed network of spatial representations in crossmodal integration. Finally, the results suggest that the temporo-parietal junction may be involved in aspects of controlling spatial attention, for both vision and touch. A multimodal attentional system may influence activity in distinct brain areas representing common regions of space for different modalities, thus suggesting a link between spatial attention and crossmodal integration.

Selective attention allows people to process some stimuli more thoroughly than others. This is partly under voluntary control, and partly determined by stimulus salience. Selective attention has been studied with psychological methods for many years, but recent cognitive neuroscience studies using brain-imaging methods (and other neurobiological measures) have transformed the topic. Such studies have demonstrated that sensory processing can be strongly modulated by attention throughout perceptual networks, including even processing in primary sensory cortex. They have shown that some of these modulations can be anticipatory, arising prior to stimulus presentation, while other components reflect a changed neural response to an incoming stimulus. Recent imaging studies have also examined the mechanisms involved in controlling such attentional modulation of sensory processing. In addition to answering many long-standing questions about selective attention, such research also raises new questions. The various contributions in this volume provide an overview of the spectacular recent advances in attention research using neurobiological measures, and they outline critical issues to be resolved in the future.

When observing ourselves in a mirror, we see our body and adjacent objects (e.g. a comb or razor) projecting the image of distant objects. Are these recoded by the brain as reflecting stimuli in peripersonal space? To address this, we exploited the neuropsychological phenomenon of crossmodal, visual-tactile extinction, as shown by patient BV following right-hemisphere stroke. In such crossmodal extinction, a right visual event impairs the perception of a simultaneous left tactile event. In BV, the right visual stimulus (an LED flash) induced more extinction of touch on the contralesional left hand when presented near the ipsilesional right hand, than when distant from it. This agrees with previous data in patients and monkeys showing that visual-tactile interactions are strongest within peripersonal space. Crucially, we also found that an ipsilesional flash produced more extinction when observed as the distant mirror-reflection of an LED that lay close to the ipsilesional hand, rather than as a distant LED flash projecting an equivalent visual image directly. This suggests that in BV, seeing his own hand via a mirror activates a representation of peripersonal space around that hand, not of the extrapersonal space suggested by the distant visual image in the mirror. We discuss the possible neural basis of interpreting mirror reflections.

Psychophysical and physiological studies have shown that attending to a stimulus can enhance its sensory processing. Functional imaging studies now reveal that attention can also modulate activity in sensory brain areas before stimulus onset, when the observer prepares to attend to an anticipated stimulus. These preparatory 'baseline shifts' in brain activity pose many new questions, and potentially offer new insights into the neural basis of perceptual awareness.

Recent research on multisensory perception suggests a number of general principles for crossmodal integration and that the standard model in the field--feedforward convergence of information--must be modified to include a role for feedback projections from multimodal to unimodal brain areas.

A great deal is now known about the effects of spatial attention within individual sensory modalities, especially for vision and audition. However, there has been little previous study of possible cross-modal links in attention. Here, we review recent findings from our own experiments on this topic, which reveal extensive spatial links between the modalities. An irrelevant but salient event presented within touch, audition, or vision, can attract covert spatial attention in the other modalities (with the one exception that visual events do not attract auditory attention when saccades are prevented). By shifting receptors in one modality relative to another, the spatial coordinates of these cross-modal interactions can be examined. For instance, when a hand is placed in a new position, stimulation of it now draws visual attention to a correspondingly different location, although some aspects of attention do not spatially remap in this way. Cross-modal links are also evident in voluntary shifts of attention. When a person strongly expects a target in one modality (e.g. audition) to appear in a particular location, their judgements improve at that location not only for the expected modality but also for other modalities (e.g. vision), even if events in the latter modality are somewhat more likely elsewhere. Finally, some of our experiments suggest that information from different sensory modalities may be integrated preattentively, to produce the multimodal internal spatial representations in which attention can be directed. Such preattentive cross-modal integration can, in some cases, produce helpful illusions that increase the efficiency of selective attention in complex scenes.

Several lines of evidence demonstrate that faces undergo specialized processing within the primate visual system. It has been claimed that dedicated modules for such biologically significant stimuli operate in a mandatory fashion whenever their triggering input is presented. However, the possible role of covert attention to the activating stimulus has never been examined for such cases. We used functional magnetic resonance imaging to test whether face-specific activity in the human fusiform face area (FFA) is modulated by covert attention. The FFA was first identified individually in each subject as the ventral occipitotemporal region that responded more strongly to visually presented faces than to other visual objects under passive central viewing. This then served as the region of interest within which attentional modulation was tested independently, using active tasks and a very different stimulus set. Subjects viewed brief displays each comprising two peripheral faces and two peripheral houses (all presented simultaneously). They performed a matching task on either the two faces or the two houses, while maintaining central fixation to equate retinal stimulation across tasks. Signal intensity was reliably stronger during face-matching than house matching in both right- and left-hemisphere predefined FFAs. These results show that face-specific fusiform activity is reduced when stimuli appear outside (vs. inside) the focus of attention. Despite the modular nature of the FFA (i.e., its functional specificity and anatomic localization), face processing in this region nonetheless depends on voluntary attention.

It is currently controversial whether auditory events produce inhibition of return (IOR). Although some authors argue that this can arise, others propose that peripheral auditory cues do not produce the characteristic IOR pattern of delayed detection latencies for ipsilaterally presented auditory or visual targets, unless a saccade is made to the cued location. We suggest that these previous discrepancies may depend on whether attention is reoriented centrally following the peripheral sound. We presented spatially uninformative peripheral auditory cues prior to visual targets requiring speeded detection responses. IOR was found in the absence of eye movements, provided an auditory reorienting event was presented at central fixation between onset of the peripheral cue and the subsequent target, but not when the central reorienting event was visual. A subsequent experiment demonstrated that auditory IOR between successive targets is similarly significantly reduced in the absence of an appropriate central reorienting event. These results imply that auditory stimuli can induce IOR directly. Previous failures to demonstrate IOR following auditory cues may have been due to an opposing influence of long-lasting attentional facilitation at the cued location, rather than to the putative inability of auditory stimuli to engage oculomotor processes generating IOR.

During sleep there is a two- to threefold increase in the incorporation of inorganic orthophosphate-(32)P into a chemical fraction of the brain of the 20-day-old rat. This increase is not in the lipids or nucleic acids, but is associated with an acid-labile phosphate entity of the tissue residue after extraction of these fractions and phosphorus-containing substances of low molecular weight.

Though all in vitro models of gamma frequency network oscillations are critically dependent on GABAA receptor-mediated synaptic transmission little is known about the specific role played by different subtypes of GABAA receptor. Strong expression of the α5 subunit of the GABAA receptor is restricted to few brain regions, amongst them the hippocampal dendritic layers. Receptors containing this subunit may be expressed on the extrasynaptic membrane of principal cells and can mediate a tonic GABAA conductance. Using hippocampal slices of wild-type (WT) and α5-/- mice we investigated the role of α5 subunits in the generation of kainate-induced gamma frequency oscillations (20-80 Hz). The change in power of the oscillations evoked in CA3 by increasing network drive (kainate, 50-400 nM) was significantly greater in α5-/- than in WT slices. However, the change in frequency of gamma oscillations with increasing network drive seen in WT slices was absent in α5-/- slices. Raising the concentration of extracellular GABA by bathing slices in the GABA transaminase inhibitor vigabatrin and blocking uptake with tiagabine reduced the power of gamma oscillations more in WT slices than α5-/- slices (43% versus 15%). The data suggest that loss of this GABAA receptor subunit alters the dynamic profile of gamma oscillations to changes in network drive, possibly via actions of GABA at extrasynaptic receptors. [ABSTRACT FROM AUTHOR]

Event-related functional magnetic resonance imaging was used to identify brain areas involved in spatial attention and determine whether these operate unimodally or supramodally for vision and touch. On a trial-by-trial basis, a symbolic auditory cue indicated the most likely side for the subsequent target, thus directing covert attention to one side. A subsequent target appeared in vision or touch on the cued or uncued side. Invalidly cued trials (as compared with valid trials) activated the temporo-parietal junction and regions of inferior frontal cortex, regardless of target modality. These brain areas have been associated with multimodal spatial coding in physiological studies of the monkey brain and were linked to a change in the location that must be attended to in the present study. The intraparietal sulcus and superior frontal cortex were also activated in our task, again, regardless of target modality, but did not show any specificity for invalidly cued trials. These results identify a supramodal network for spatial attention and reveal differential activity for inferior circuits involving the temporo-parietal junction and inferior frontal cortex (specific to invalid trials) versus more superior intraparietal-frontal circuits (common to valid and invalid trials). [ABSTRACT FROM AUTHOR]