Four Functionally Distinct Regions in the Left Supramarginal Gyrus Support Word Processing.

We used fMRI in 85 healthy participants to investigate whether different parts of the left supramarginal gyrus (SMG) are involved in processing phonological inputs and outputs. The experiment involved 2 tasks (speech production (SP) and one-back (OB) matching) on 8 different types of stimuli that systematically varied the demands on sensory processing (visual vs. auditory), sublexical phonological input (words and pseudowords vs. nonverbal stimuli), and semantic content (words and objects vs. pseudowords and meaningless baseline stimuli). In ventral SMG, we found an anterior subregion associated with articulatory sequencing (for SP > OB matching) and a posterior subregion associated with auditory short-term memory (for all auditory > visual stimuli and written words and pseudowords > objects). In dorsal SMG, a posterior subregion was most highly activated by words, indicating a role in the integration of sublexical and lexical cues. In anterior dorsal SMG, activation was higher for both pseudoword reading and object naming compared with word reading, which is more consistent with executive demands than phonological processing. The dissociation of these four "functionally-distinct" regions, all within left SMG, has implications for differentiating between different types of phonological processing, understanding the functional anatomy of language and predicting the effect of brain damage.

Reading front to back: MEG evidence for early feedback effects during word recognition.

Magnetoencephalography studies in humans have shown word-selective activity in the left inferior frontal gyrus (IFG) approximately 130 ms after word presentation ( Pammer et al. 2004; Cornelissen et al. 2009; Wheat et al. 2010). The role of this early frontal response is currently not known. We tested the hypothesis that the IFG provides top-down constraints on word recognition using dynamic causal modeling of magnetoencephalography data collected, while subjects viewed written words and false font stimuli. Subject-specific dipoles in left and right occipital, ventral occipitotemporal and frontal cortices were identified using Variational Bayesian Equivalent Current Dipole source reconstruction. A connectivity analysis tested how words and false font stimuli differentially modulated activity between these regions within the first 300 ms after stimulus presentation. We found that left inferior frontal activity showed stronger sensitivity to words than false font and a stronger feedback connection onto the left ventral occipitotemporal cortex (vOT) in the first 200 ms. Subsequently, the effect of words relative to false font was observed on feedforward connections from left occipital to ventral occipitotemporal and frontal regions. These findings demonstrate that left inferior frontal activity modulates vOT in the early stages of word processing and provides a mechanistic account of top-down effects during word recognition.

Multiwavelength interferometry system for the Orion laser facility.

We report on the design and testing of a multiwavelength interferometry system for the Orion laser facility based upon the use of self-path matching Wollaston prisms. The use of UV corrected achromatic optics allows for both easy alignment with an eye-safe light source and small (∼ millimeter) offsets to the focal lengths between different operational wavelengths. Interferograms are demonstrated at wavelengths corresponding to first, second, and fourth harmonics of a 1054 nm Nd:glass probe beam. Example data confirms the broadband achromatic capability of the imaging system with operation from the UV (263 nm) to visible (527 nm) and demonstrates that features as small as 5 µm can be resolved for object sizes of 15 by 10 mm. Results are also shown for an off-harmonic wavelength that will underpin a future capability. The primary optics package is accommodated inside the footprint of a ten-inch manipulator to allow the system to be deployed from a multitude of viewing angles inside the 4 m diameter Orion target chamber.

How number processing survives left occipito-temporal damage.

We investigated the neural systems that support number processing in a patient (JL) who had damage to the left ventral occipito-temporal cortex (LvOT). JL had severely impaired written word recognition but he was remarkably accurate in number tasks, albeit slower than normal. This suggests LvOT activation is necessary for efficient but not for accurate number decisions. Here we investigated how JL made accurate number decisions using fMRI; we compared JL's brain activation to that in healthy controls and in two patients with frontal lobe damage who, like JL, made slow but accurate responses in number tasks. For semantic relative to perceptual decisions on numbers, JL did not activate the left occipito-temporal area that was involved in all other subjects. However, JL had significantly increased activation in a left posterior middle temporal region. In addition, during semantic and perceptual decisions on numbers, JL showed increased activation in: (1) the right occipito-temporal cortex, (2) right caudate, and (3) bilateral frontal regions. These effects were unique to JL and cannot be explained in terms of abnormally long response times because they were not observed in the other patients who made slow but accurate number decisions. Together these results show that although the LvOT usually contributes to efficient number processing, activation in this region is not essential for accurate performance because (i) perceptual processing of numbers can be supported by right occipital, right caudate, and bilateral frontal activation and (ii) semantic processing of numbers can be supported by increased left posterior middle temporal activation associated with hand actions.

Gray and white matter changes associated with tool-use learning in macaque monkeys.

We used noninvasive MRI and voxel-based morphometry (VBM) to detect changes in brain structure in three adult Japanese macaques trained to use a rake to retrieve food rewards. Monkeys, who were naive to any previous tool use, were scanned repeatedly in a 4-T scanner over 6 weeks, comprising 2 weeks of habituation followed by 2 weeks of intensive daily training and a 2-week posttraining period. VBM analysis revealed significant increases in gray matter with rake performance across the three monkeys. The effects were most significant (P < 0.05 corrected for multiple comparisons across the whole brain) in the right superior temporal sulcus, right second somatosensory area, and right intraparietal sulcus, with less significant effects (P < 0.001 uncorrected) in these same regions of the left hemisphere. Bilateral increases were also observed in the white matter of the cerebellar hemisphere in lobule 5. In two of the monkeys who exhibited rapid learning of the rake task, gray matter volume in peak voxels increased by up to 17% during the intensive training period; the earliest changes were seen after 1 week of intensive training, and they generally peaked when performance on the task plateaued. In the third monkey, who was slower to learn the task, peak voxels showed no systematic changes. Thus, VBM can detect significant brain changes in individual trained monkeys exposed to tool-use training for the first time. This approach could open up a means of investigating the underlying neurobiology of motor learning and other higher brain functions in individual animals.

Changing meaning causes coupling changes within higher levels of the cortical hierarchy.

Processing of speech and nonspeech sounds occurs bilaterally within primary auditory cortex and surrounding regions of the superior temporal gyrus; however, the manner in which these regions interact during speech and nonspeech processing is not well understood. Here, we investigate the underlying neuronal architecture of the auditory system with magnetoencephalography and a mismatch paradigm. We used a spoken word as a repeating "standard" and periodically introduced 3 "oddball" stimuli that differed in the frequency spectrum of the word's vowel. The closest deviant was perceived as the same vowel as the standard, whereas the other 2 deviants were perceived as belonging to different vowel categories. The neuronal responses to these vowel stimuli were compared with responses elicited by perceptually matched tone stimuli under the same paradigm. For both speech and tones, deviant stimuli induced coupling changes within the same bilateral temporal lobe system. However, vowel oddball effects increased coupling within the left posterior superior temporal gyrus, whereas perceptually equivalent nonspeech oddball effects increased coupling within the right primary auditory cortex. Thus, we show a dissociation in neuronal interactions, occurring at both different hierarchal levels of the auditory system (superior temporal versus primary auditory cortex) and in different hemispheres (left versus right). This hierarchical specificity depends on whether auditory stimuli are embedded in a perceptual context (i.e., a word). Furthermore, our lateralization results suggest left hemisphere specificity for the processing of phonological stimuli, regardless of their elemental (i.e., spectrotemporal) characteristics.

Creating a population-averaged standard brain template for Japanese macaques (M. fuscata).

A number of modern digital anatomy techniques, based on structural MR brain images, have recently become applicable to the non-human primate brain. Such voxel-based quantitative techniques require a species-specific standardized brain template. Here we present a brain template for the Japanese macaque (Macaca fuscata). The template was designed to be used as a tool for spatially normalising Japanese macaque brains into a standard space. Although this species of macaque monkey is widely used in neuroscience research, including studies of higher cognitive brain functions, no standard MRI template of its brain is presently available. The template presented here is based on T1/T2* weighted, high-resolution 4T MR images obtained from 16 male adult Japanese macaque monkeys. T1/T2* images were used to correct the signal inequalities resulting from the use of a surface coil. Based on these images, population-averaged probability maps were created for grey matter, white matter and cerebrospinal fluid. The new template presented here should facilitate future brain research using the Japanese macaque monkey. Whole brain templates are available at http://brainatlas.brain.riken.jp/jm/modules/xoonips/listitem.php?index_id=9.

Integrating visual and tactile information in the perirhinal cortex.

By virtue of its widespread afferent projections, perirhinal cortex is thought to bind polymodal information into abstract object-level representations. Consistent with this proposal, deficits in cross-modal integration have been reported after perirhinal lesions in nonhuman primates. It is therefore surprising that imaging studies of humans have not observed perirhinal activation during visual-tactile object matching. Critically, however, these studies did not differentiate between congruent and incongruent trials. This is important because successful integration can only occur when polymodal information indicates a single object (congruent) rather than different objects (incongruent). We scanned neurologically intact individuals using functional magnetic resonance imaging (fMRI) while they matched shapes. We found higher perirhinal activation bilaterally for cross-modal (visual-tactile) than unimodal (visual-visual or tactile-tactile) matching, but only when visual and tactile attributes were congruent. Our results demonstrate that the human perirhinal cortex is involved in cross-modal, visual-tactile, integration and, thus, indicate a functional homology between human and monkey perirhinal cortices.

Data warehousing methods and processing infrastructure for brain recovery research.

In order to accelerate translational neuroscience with the goal of improving clinical care it has become important to support rapid accumulation and analysis of large, heterogeneous neuroimaging samples and their metadata from both normal control and patient groups. We propose a multi-centre, multinational approach to accelerate the data mining of large samples and facilitate data-led clinical translation of neuroimaging results in stroke. Such data-driven approaches are likely to have an early impact on clinically relevant brain recovery while we simultaneously pursue the much more challenging model-based approaches that depend on a deep understanding of the complex neural circuitry and physiological processes that support brain function and recovery. We present a brief overview of three (potentially converging) approaches to neuroimaging data warehousing and processing that aim to support these diverse methods for facilitating prediction of cognitive and behavioral recovery after stroke, or other types of brain injury or disease.

Lesion sites that predict the ability to gesture how an object is used.

We used a two stage procedure to predict which stroke patients would have chronic difficulties gesturing how to use an object when object recognition and hand movements were intact. First, we searched our PLORAS database by behavior and identified 5 patients who had chronic difficulty gesturing object use but no difficulty recognising objects, comprehending words or moving their hands. High definition lesion analyses showed that all 5 patients had damage to the white matter underlying the left ventral supramarginal gyrus, (A) close to the cortex, (B) deep towards the midline and (C) extending into the temporal lobe. In addition, 2 patients had damage to (D) the left posterior middle temporal cortex, and 3 patients had damage to (E) the left dorsal supramarginal gyrus and (F) the left premotor cortex. Second, we searched our database by lesion location for patients who had damage to any part of regions ABCDEF. The incidence of gesturing difficulties was higher in patients with damage to ABCD (7/9), ABCE (7/10) or ABCDE (10/13) than ABCF (7/13), ABC (8/16) or partial damage to ABCF (6/32). Thus behaviour was best predicted by the combination of regions that were damaged (a "network-lesion") rather than on the basis of each region alone or overall lesion size. Our results identify which parts of the temporal and parietal lobes impair the ability to gesture object use and which parts need to be intact to support it after damage. Our methods provide a framework for future studies aiming to predict the consequences of brain damage.

Cross-modal plasticity underpins language recovery after cochlear implantation.

Postlingually deaf subjects learn the meaning of sounds after cochlear implantation by forming new associations between sounds and their sources. Implants generate coarse frequency responses, preventing place-coding fine enough to discriminate sounds with similar temporal characteristics, e.g., buck/duck. This limitation imposes a dependency on visual cues, e.g., lipreading. We hypothesized that cross-modal facilitation results from engagement of the visual cortex by purely auditory tasks. In four functional neuroimaging experiments, we show recruitment of early visual cortex (V1/V2) when cochlear implant users listen to sounds with eyes closed. Activity in visual cortex evolved in a stimulus-specific manner as a function of time from implantation reflecting experience-dependent adaptations in the postimplant phase.

Inter-subject variability in the use of two different neuronal networks for reading aloud familiar words.

Cognitive models of reading predict that high frequency regular words can be read in more than one way. We investigated this hypothesis using functional MRI and covariance analysis in 43 healthy skilled readers. Our results dissociated two sets of regions that were differentially engaged across subjects who were reading the same familiar words. Some subjects showed more activation in left inferior frontal and anterior occipito-temporal regions while other subjects showed more activation in right inferior parietal and left posterior occipito-temporal regions. To explore the behavioural correlates of these systems, we measured the difference between reading speed for irregularly spelled words relative to pseudowords outside the scanner in fifteen of our subjects and correlated this measure with fMRI activation for reading familiar words. The faster the lexical reading the greater the activation in left posterior occipito-temporal and right inferior parietal regions. Conversely, the slower the lexical reading the greater the activation in left anterior occipito-temporal and left ventral inferior frontal regions. Thus, the double dissociation in irregular and pseudoword reading behaviour predicted the double dissociation in neuronal activation for reading familiar words. We discuss the implications of these results which may be important for understanding how reading is learnt in childhood or re-learnt following brain damage in adulthood.

Prevalence of Campylobacter and four endoparasites in dog populations associated with Hearing Dogs.

OBJECTIVES: This study established the prevalence of four gastrointestinal parasites (Isopora species, Giardia species, Uncinaria stenocephala, Toxocara canis) and one bacterial infection (Campylobacter jejuni/coli) in dogs associated with the charity Hearing Dogs for Deaf People. METHODS: Dogs' faeces were routinely sampled from dogs according to whether they were in Socialising, Kennelling or Visiting the Hearing Dogs site. A further group consisted of dogs with diarrhoea. RESULTS: Prevalence rates for dogs in Socialising (n=326), Kennelling (n=117), Visiting (n=106) and Diarrhoea (n=59) groups, respectively, were as follows: Campylobacter- 26, 21, 15 and 31 per cent; Coccidia - 3, 0, 0 and 2 per cent; Giardia- 13, 3, 2 and 10 per cent; hookworm - 1, 1, 4 and 5 per cent; and Toxocara- 4, 2, 3 and 2 per cent. There were significant differences in the levels of Giardia and hookworm found between the four different groups of dogs. No significant gender differences were found, and dogs that were positive for Campylobacter in the Visiting group were significantly younger. CLINICAL SIGNIFICANCE: This study provides current information on the infection rates in specific dog populations in the UK. This is relevant to the veterinary health of dogs and the possible risk of zoonotic infection to humans.

Respiratory sinus arrhythmia as a potential measure in substance use treatment--outcome studies.

BACKGROUND AND AIMS: Dysfunction of physiological regulation systems may underlie the disrupted emotional and self-regulatory processes among people with substance use disorder (SUD). This paper reviews evidence as to whether or not respiratory sinus arrhythmia (RSA), as a psychophysiological index of emotional regulation, could provide useful information in treatment-outcome research to provide insights into recovery processes. METHODS: We reviewed the use of RSA in clinical research and studies on SUD treatment. Search terms for the review of RSA in clinical research included respiratory sinus arrhythmia, heart rate variability, vagal, cardiac vagal control, psychophysiology, intervention, treatment, mindfulness, mind-body, mental health, substance use, chemical dependence, regulation and emotion regulation. For the review of RSA in intervention studies, we included only those that provided adequate description of psychophysiological methods, and examined RSA in the context of an intervention study. RESULTS: RSA appears to be able to provide an index of self-regulatory capacity; however, it has been little used in either intervention or treatment research. Of the four intervention studies included in this review, all were mindfulness-based interventions. Two studies were with substance-using samples, and both showed pre-post increases in RSA and related improved substance use outcomes. Two of the three studies were randomized controlled trials (RCTs), and both showed significant increases in RSA in the experimental compared to comparison condition. CONCLUSION: Respiratory sinus arrhythmia may be a useful index of emotional regulation in people with substance use disorder, and a potential measure of underlying mechanisms for SUD treatment studies, particularly mindfulness-based interventions.

Neural changes in the primate brain correlated with the evolution of complex motor skills.

Complex motor skills of eventual benefit can be learned after considerable trial and error. What do structural brain changes that accompany such effortful long-term learning tell us about the mechanisms for developing innovative behavior? Using MRI, we monitored brain structure before, during and after four marmosets learnt to use a rake, over a long period of 10-13 months. Throughout learning, improvements in dexterity and visuo-motor co-ordination correlated with increased volume in the lateral extrastriate cortex. During late learning, when the most complex behavior was maintained by sustained motivation to acquire the skill, the volume of the nucleus accumbens increased. These findings reflect the motivational state required to learn, and show accelerated function in higher visual cortex that is consistent with neurocognitive divergence across a spectrum of primate species.

The functional anatomy of word comprehension and production.

This review describes the functional anatomy of word comprehension and production. Data from functional neuroimaging studies of normal subjects are used to determine the distributed set of brain regions that are engaged during particular language tasks and data from studies of patients with neurological damage are used to determine which of these regions are necessary for task performance. This combination of techniques indicates that the left inferior temporal and left posterior inferior parietal cortices are required for accessing semantic knowledge; the left posterior basal temporal lobe and the left frontal operculum are required for translating semantics into phonological output and the left anterior inferior parietal cortex is required for translating orthography to phonology. Further studies are required to establish the specific functions of the different regions and how these functions interact to provide our sophisticated language system.

Action selectivity in parietal and temporal cortex.

The sensory-action theory proposes that the neural substrates underlying action representations are related to a visuomotor action system encompassing the left ventral premotor cortex, the anterior intraparietal (AIP) and left posterior middle temporal gyrus (LPMT). Using fMRI, we demonstrate that semantic decisions on action, relative to non-action words, increased activation in the left AIP and LPMT irrespective of whether the words were presented in a written or spoken form. Left AIP and LPMT might thus play the role of amodal semantic regions that can be activated via auditory as well as visual input. Left AIP and LPMT did not distinguish between different types of actions such as hand actions and whole body movements, although a right STS region responded selectively to whole body movements.

Vasodilator-stimulated phosphoprotein is involved in stress-fiber and membrane ruffle formation in endothelial cells.

Vasodilator-stimulated phosphoprotein (VASP) is highly expressed in vascular endothelial cells, where it has been implicated in cellular reorganization during angiogenesis, as well as in endothelial retraction and changes in vessel permeability. However, the cellular functions of VASP are not known. In this study, we have expressed wild-type and mutant forms of VASP in endothelial cells to determine in what aspects of cytoskeletal behavior this protein participates. Expression of wild-type VASP induces marked membrane ruffling and formation of prominent stress fibers in bovine aortic endothelial cells. Deletion of the proline-rich domain of VASP abolishes its ability to bind profilin but does not affect ruffling or stress fiber formation. Further deletions reveal a sequence within the carboxy-terminal domain that is responsible for in vivo bundle formation. Ruffling occurs only on the expression of forms of VASP that possess bundling activity and the capacity to bind zyxin/vinculin-derived peptide. The ability of distinct subdomains within VASP to bind adhesion proteins and induce F-actin bundling in vivo suggests that this protein could function in the aggregation and tethering of actin filaments during the formation of endothelial cell-substrate and cell-cell contacts. These data provide a mechanism whereby VASP can influence endothelial migration and organization during capillary formation and modulate vascular permeability via effects on endothelial cell contractility.

An in-vacuo optical levitation trap for high-intensity laser interaction experiments with isolated microtargets.

We report on the design, construction, and characterisation of a new class of in-vacuo optical levitation trap optimised for use in high-intensity, high-energy laser interaction experiments. The system uses a focused, vertically propagating continuous wave laser beam to capture and manipulate micro-targets by photon momentum transfer at much longer working distances than commonly used by optical tweezer systems. A high speed (10 kHz) optical imaging and signal acquisition system was implemented for tracking the levitated droplets position and dynamic behaviour under atmospheric and vacuum conditions, with ±5 µm spatial resolution. Optical trapping of 10 ± 4 µm oil droplets in vacuum was demonstrated, over timescales of >1 h at extended distances of ∼40 mm from the final focusing optic. The stability of the levitated droplet was such that it would stay in alignment with a ∼7 µm irradiating beam focal spot for up to 5 min without the need for re-adjustment. The performance of the trap was assessed in a series of high-intensity (10(17) W cm(-2)) laser experiments that measured the X-ray source size and inferred free-electron temperature of a single isolated droplet target, along with a measurement of the emitted radio-frequency pulse. These initial tests demonstrated the use of optically levitated microdroplets as a robust target platform for further high-intensity laser interaction and point source studies.

Cerebral neutrophil recruitment, histology, and outcome in acute ischemic stroke: an imaging-based study.

BACKGROUND AND PURPOSE: Evidence now exists for a pathogenic role for neutrophils in acute cerebral ischemia. We have studied the patterns and temporal profile of cerebral neutrophil recruitment to areas of acute ischemic stroke (IS) and have attempted to correlate this with neurological status and outcome. METHODS: Patients with cortical middle cerebral artery (MCA) IS were recruited within 24 hours of clinical onset. Neutrophil recruitment was studied using indium-111 (111In) troponolate-labeled neutrophils, planar imaging, and single-photon emission computed tomography (SPECT). Volume of brain infarction was calculated from concurrent computed tomography (CT). Hematoxylin and eosin sections were obtained postmortem (n=2). Outcome was measured using Barthel, Rankin, and National Institute of Health Stroke (NIHSS) scales. RESULTS: Fifteen patients were studied. Significant 111In-neutrophil recruitment to ipsilateral hemisphere, as measured by asymmetry index (AI), was demonstrated within 24 hours of onset in 9 patients; this response was heterogenous between patients and on repeated measurement attenuated over time. Histologically, recruitment was confirmed within intravascular, intramural, and intraparenchymal compartments. Interindividual heterogeneity in neutrophil response did not correlate with infarct volume or outcome. In an exploratory analysis, neutrophil accumulation appeared to correlate significantly with infarct expansion (Spearman rho=0.66; P=0.03, n=12). CONCLUSIONS: Neutrophils recruit to areas of ischemic brain within 24 hours of symptom onset. This recruitment attenuates over time and is confirmed histologically. While neutrophil accumulation may be associated with either the magnitude or the rate of infarct growth, these results require confirmation in future studies.