Richard J S Wise

Imperial College London, Londinium, England, United Kingdom

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Publications (163)1214.92 Total impact

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    ABSTRACT: Blood oxygenation level-dependent (BOLD) contrast functional magnetic resonance imaging (fMRI) is a widely used technique to map brain function, and to monitor its recovery after stroke. Since stroke has a vascular etiology, the neurovascular coupling between cerebral blood flow and neural activity may be altered, resulting in uncertainties when interpreting longitudinal BOLD signal changes. The purpose of this study was to demonstrate the feasibility of using a recently validated breath-hold task in patients with stroke, both to assess group level changes in cerebrovascular reactivity (CVR) and to determine if alterations in regional CVR over time will adversely affect interpretation of task-related BOLD signal changes. Three methods of analyzing the breath-hold data were evaluated. The CVR measures were compared over healthy tissue, infarcted tissue and the peri-infarct tissue, both sub-acutely (∼2 weeks) and chronically (∼4 months). In this cohort, a lack of CVR differences in healthy tissue between the patients and controls indicates that any group level BOLD signal change observed in these regions over time is unlikely to be related to vascular alterations. CVR was reduced in the peri-infarct tissue but remained unchanged over time. Therefore, although a lack of activation in this region compared with the controls may be confounded by a reduced CVR, longitudinal group-level BOLD changes may be more confidently attributed to neural activity changes in this cohort. By including this breath-hold-based CVR assessment protocol in future studies of stroke recovery, researchers can be more assured that longitudinal changes in BOLD signal reflect true alterations in neural activity. Hum Brain Mapp, 2015. © 2014 Wiley Periodicals, Inc. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.
    Human Brain Mapping 02/2015; 36(5). DOI:10.1002/hbm.22735 · 6.92 Impact Factor
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    ABSTRACT: Remembering what a speaker said depends on attention. During conversational speech, the emphasis is on working memory, but listening to a lecture encourages episodic memory encoding. With simultaneous interference from background speech, the need for auditory vigilance increases. We recreated these context-dependent demands on auditory attention in 2 ways. The first was to require participants to attend to one speaker in either the absence or presence of a distracting background speaker. The second was to alter the task demand, requiring either an immediate or delayed recall of the content of the attended speech. Across 2 fMRI studies, common activated regions associated with segregating attended from unattended speech were the right anterior insula and adjacent frontal operculum (aI/FOp), the left planum temporale, and the precuneus. In contrast, activity in a ventral right frontoparietal system was dependent on both the task demand and the presence of a competing speaker. Additional multivariate analyses identified other domain-general frontoparietal systems, where activity increased during attentive listening but was modulated little by the need for speech stream segregation in the presence of 2 speakers. These results make predictions about impairments in attentive listening in different communicative contexts following focal or diffuse brain pathology. © The Author 2015. Published by Oxford University Press.
    Cerebral Cortex 01/2015; DOI:10.1093/cercor/bhu325 · 8.31 Impact Factor
  • Fatemeh Geranmayeh, Robert Leech, Richard J S Wise
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    ABSTRACT: Retrieval of semantic representations is a central process during overt speech production. There is an increasing consensus that an amodal semantic 'hub' must exist that draws together modality-specific representations of concepts. Based on the distribution of atrophy and the behavioral deficit of patients with the semantic variant of fronto-temporal lobar degeneration, it has been proposed that this hub is localized within both anterior temporal lobes (ATL), and is functionally connected with verbal 'output' systems via the left ATL. An alternative view, dating from Geschwind's proposal in 1965, is that the angular gyrus (AG) is central to object-based semantic representations. In this fMRI study we examined the connectivity of the left ATL and parietal lobe (PL) with whole brain networks known to be activated during overt picture description. We decomposed each of these two brain volumes into 15 regions of interest (ROIs), using independent component analysis. A dual regression analysis was used to establish the connectivity of each ROI with whole brain-networks. An ROI within the left anterior superior temporal sulcus (antSTS) was functionally connected to other parts of the left ATL, including anterior ventromedial left temporal cortex (partially attenuated by signal loss due to susceptibility artifact), a large left dorsolateral prefrontal region (including 'classic' Broca's area), extensive bilateral sensory-motor cortices, and the length of both superior temporal gyri. The time-course of this functionally connected network was associated with picture description but not with non-semantic baseline tasks. This system has the distribution expected for the production of overt speech with appropriate semantic content, and the auditory monitoring of the overt speech output. In contrast, the only left PL ROI that showed connectivity with brain systems most strongly activated by the picture-description task, was in the superior parietal lobe (supPL). This region showed connectivity with predominantly posterior cortical regions required for the visual processing of the pictorial stimuli, with additional connectivity to the dorsal left AG and a small component of the left inferior frontal gyrus. None of the other PL ROIs that included part of the left AG were activated by Speech alone. The best interpretation of these results is that the left antSTS connects the proposed semantic hub (specifically localized to ventral anterior temporal cortex based on clinical neuropsychological studies) to posterior frontal regions and sensory-motor cortices responsible for the overt production of speech. Copyright © 2014. Published by Elsevier Ltd.
    Neuropsychologia 12/2014; DOI:10.1016/j.neuropsychologia.2014.12.012 · 3.45 Impact Factor
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    ABSTRACT: We present two patients in whom the combination of lesion site and cognitive performance was uniquely informative about the organisation and functional anatomy of semantic memory. One had had a single lobar stroke with an unusual distribution, largely destroying the whole of the left temporal lobe ventral to the superior temporal sulcus. The other patient had had herpes simplex encephalitis with destruction that was confined to the left cerebral hemisphere. The lesion again mainly encompassed the left temporal lobe, but also extended to the left inferior frontal gyrus. Cognitive outcomes in the two patients were compared with each other and with published results from patients with semantic dementia. This is because, whereas the majority of semantic dementia patients present with more prominent atrophy of the left rostroventral temporal lobe, they invariably have a degree of atrophy in the mirror region on the right that progresses. Semantic dementia therefore provides no clear evidence about the specific role of the left rostroventral temporal lobe. The two patients showed a highly consistent cognitive profile. Their deficits were also similar in many respects to that observed in patients with mild-moderate semantic dementia, including severe anomia that was not resolved by phonological cues and impairment on non-verbal as well as verbal semantic tasks. Certain key features of the semantic dementia profile, however-including sensitivity to the familiarity and typicality of the stimulus materials-appeared only in tasks requiring verbal output in these two patients with unilateral left temporal lesions. Results in these cases provide some of the first definitive evidence regarding the specific functions of the left anterior temporal lobe. Copyright © 2014. Published by Elsevier Ltd.
    Neuropsychologia 11/2014; DOI:10.1016/j.neuropsychologia.2014.11.024 · 3.45 Impact Factor
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    ABSTRACT: Speech production relies on fine voluntary motor control of respiration, phonation, and articulation. The cortical initiation of complex sequences of coordinated movements is thought to result in parallel outputs, one directed toward motor neurons while the "efference copy" projects to auditory and somatosensory fields. It is proposed that the latter encodes the expected sensory consequences of speech and compares expected with actual postarticulatory sensory feedback. Previous functional neuroimaging evidence has indicated that the cortical target for the merging of feedforward motor and feedback sensory signals is left-lateralized and lies at the junction of the supratemporal plane with the parietal operculum, located mainly in the posterior half of the planum temporale (PT). The design of these studies required participants to imagine speaking or generating nonverbal vocalizations in response to external stimuli. The resulting assumption is that verbal and nonverbal vocal motor imagery activates neural systems that integrate the sensory-motor consequences of speech, even in the absence of primary motor cortical activity or sensory feedback. The present human functional magnetic resonance imaging study used univariate and multivariate analyses to investigate both overt and covert (internally generated) propositional and nonpropositional speech (noun definition and counting, respectively). Activity in response to overt, but not covert, speech was present in bilateral anterior PT, with no increased activity observed in posterior PT or parietal opercula for either speech type. On this evidence, the response of the left and right anterior PTs better fulfills the criteria for sensory target and state maps during overt speech production.
    The Journal of Neuroscience : The Official Journal of the Society for Neuroscience 09/2014; 34(39):12963-72. DOI:10.1523/JNEUROSCI.0336-14.2014 · 6.75 Impact Factor
  • Novraj S Dhanjal, Richard J S Wise
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    ABSTRACT: Objective: Episodic memory retrieval is reliant upon cognitive control systems, of which two have been identified with functional neuroimaging: a cingulo-opercular 'salience network' (SN), and a fronto-parietal 'executive network' (EN). In Alzheimer's disease (AD), pathology is distributed throughout higher-order cortices. The hypotheses were that this fronto-parietal pathology, would impair activity associated with verbal memory recall; and that central cholinesterase inhibition (ChI) would modulate this, improving memory recall. Methods: Functional magnetic resonance imaging was used to study normal participants and two patient groups: mild cognitive impairment (MCI) and AD. Activity within EN and SN was observed during free recall of previously heard sentences, and related to measures of recall accuracy. Results: In normals, trials with reduced recall were associated with greater activity in both SN and EN. Better recall was associated with greater activity in medial regions of the default mode network. By comparison, AD patients showed attenuated responses in both SN and EN compared with either controls or MCI patients, even after recall performance was matched between groups. Following ChI, AD patients showed no modulation of activity within SN, but increased activity within EN. There was also enhanced activity within regions associated with episodic and semantic memory, during less successful recall, requiring greater cognitive control. Interpretation: The results indicate that in AD, impaired responses of cognitive control networks during verbal memory recall are partly responsible for reduced recall performance. One action of symptom-modifying treatment is partially to reverse the abnormal function of fronto-parietal cognitive control and temporal lobe memory networks. ANN NEUROL 2014. © 2014 American Neurological Association.
    Annals of Neurology 08/2014; 76(2). DOI:10.1002/ana.24199 · 11.91 Impact Factor
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    ABSTRACT: The estimated prevalence of aphasia in the UK and the USA is 250 000 and 1 000 000, respectively. The commonest aetiology is stroke. The impairment may improve with behavioural therapy, and trials using cortical stimulation or pharmacotherapy are undergoing proof-of-principle investigation, but with mixed results. Aphasia is a heterogeneous syndrome, and the simple classifications according to the Broca-Wernicke-Lichtheim model inadequately describe the diverse communication difficulties with which patients may present. Greater knowledge of how intact neural networks promote recovery after aphasic stroke, either spontaneously or in response to interventions, will result in clearer hypotheses about how to improve the treatment of aphasia. Twenty-five years ago, a pioneering study on healthy participants heralded the introduction of functional neuroimaging to the study of mechanisms of recovery from aphasia. Over the ensuing decades, such studies have been interpreted as supporting one of three hypotheses, which are not mutually exclusive. The first two predate the introduction of functional neuroimaging: that recovery is the consequence of the reconstitution of domain-specific language systems in tissue around the lesion (the 'perilesional' hypothesis), or by homotopic cortex in the contralateral hemisphere (the 'laterality-shift' hypothesis). The third is that loss of transcallosal inhibition to contralateral homotopic cortex hinders recovery (the 'disinhibition' hypothesis). These different hypotheses at times give conflicting views about rehabilitative intervention; for example, should one attempt to activate or inhibit a contralateral homotopic region with cortical stimulation techniques to promote recovery? This review proposes that although the functional imaging data are statistically valid in most cases, their interpretation has often favoured one explanation while ignoring plausible alternatives. In our view, this is particularly evident when recovery is attributed to activity in 'language networks' occupying sites not observed in healthy participants. In this review we will argue that much of the distribution of what has often been interpreted as language-specific activity, particularly in midline and contralateral cortical regions, is an upregulation of activity in intact domain-general systems for cognitive control and attention, responding in a task-dependent manner to the increased 'effort' when damaged downstream domain-specific language networks are impaired. We further propose that it is an inability fully to activate these systems that may result in sub optimal recovery in some patients. Interpretation of the data in terms of activity in domain-general networks affords insights into novel approaches to rehabilitation.
    Brain 06/2014; 137. DOI:10.1093/brain/awu163 · 10.23 Impact Factor
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    ABSTRACT: Spoken language production is a complex brain function that relies on large-scale networks. These include domain-specific networks that mediate language-specific processes, as well as domain-general networks mediating top-down and bottom-up attentional control. Language control is thought to involve a left-lateralized fronto-temporal-parietal (FTP) system. However, these regions do not always activate for language tasks and similar regions have been implicated in nonlinguistic cognitive processes. These inconsistent findings suggest that either the left FTP is involved in multidomain cognitive control or that there are multiple spatially overlapping FTP systems. We present evidence from an fMRI study using multivariate analysis to identify spatiotemporal networks involved in spoken language production in humans. We compared spoken language production (Speech) with multiple baselines, counting (Count), nonverbal decision (Decision), and "rest," to pull apart the multiple partially overlapping networks that are involved in speech production. A left-lateralized FTP network was activated during Speech and deactivated during Count and nonverbal Decision trials, implicating it in cognitive control specific to sentential spoken language production. A mirror right-lateralized FTP network was activated in the Count and Decision trials, but not Speech. Importantly, a second overlapping left FTP network showed relative deactivation in Speech. These three networks, with distinct time courses, overlapped in the left parietal lobe. Contrary to the standard model of the left FTP as being dominant for speech, we revealed a more complex pattern within the left FTP, including at least two left FTP networks with competing functional roles, only one of which was activated in speech production.
    The Journal of Neuroscience : The Official Journal of the Society for Neuroscience 06/2014; 34(26):8728-40. DOI:10.1523/JNEUROSCI.0428-14.2014 · 6.75 Impact Factor
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    ABSTRACT: Research on mammals predicts that the anterior striatum is a central component of human motor learning. However, as vocalizations in most mammals are innate, much of the neurobiology of human vocal learning has been inferred from studies on songbirds. Essential for song learning is a pathway, the homologue of mammalian cortical-basal ganglia 'loops', which includes the avian striatum. The present functional magnetic resonance imaging (fMRI) study investigated adult human vocal learning, a skill that persists throughout life, albeit imperfectly as late-acquired languages are spoken with an accent. Monolingual adult participants were scanned while repeating novel non-native words. After training on the pronunciation of half the words for one week, they underwent a second scan. During scanning there was no external feedback on performance. Activity declined sharply in left and right anterior striatum, both within and between scanning sessions, and this change was independent of training and performance. This indicates that adult speakers rapidly adapt to the novel articulatory movements, possibly by using motor sequences from their native speech to approximate those required for the novel speech sounds. Improved accuracy correlated only with activity in motor-sensory perisylvian cortex. We propose that future studies on vocal learning, using different behavioral and pharmacological manipulations, will provide insights into adult striatal plasticity and its potential for modification in both educational and clinical contexts.
    Journal of Neurophysiology 05/2014; 112(4). DOI:10.1152/jn.00901.2013 · 3.04 Impact Factor
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    ABSTRACT: Modern neuroimaging techniques have advanced our understanding of the distributed anatomy of speech production, beyond that inferred from clinico-pathological correlations. However, much remains unknown about functional interactions between anatomically distinct components of this speech production network. One reason for this is the need to separate spatially overlapping neural signals supporting diverse cortical functions. We took three separate human functional magnetic resonance imaging (fMRI) datasets (two speech production, one "rest"). In each we decomposed the neural activity within the left posterior perisylvian speech region into discrete components. This decomposition robustly identified two overlapping spatio-temporal components, one centered on the left posterior superior temporal gyrus (pSTG), the other on the adjacent ventral anterior parietal lobe (vAPL). The pSTG was functionally connected with bilateral superior temporal and inferior frontal regions, whereas the vAPL was connected with other parietal regions, lateral and medial. Surprisingly, the components displayed spatial anti-correlation, in which the negative functional connectivity of each component overlapped with the other component's positive functional connectivity, suggesting that these two systems operate separately and possibly in competition. The speech tasks reliably modulated activity in both pSTG and vAPL suggesting they are involved in speech production, but their activity patterns dissociate in response to different speech demands. These components were also identified in subjects at "rest" and not engaged in overt speech production. These findings indicate that the neural architecture underlying speech production involves parallel distinct components that converge within posterior peri-sylvian cortex, explaining, in part, why this region is so important for speech production. Hum Brain Mapp, 2013. © 2013 Wiley Periodicals, Inc.
    Human Brain Mapping 05/2014; 35(5). DOI:10.1002/hbm.22303 · 6.92 Impact Factor
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    ABSTRACT: Understanding how dynamic changes in brain activity control behavior is a major challenge of cognitive neuroscience. Here, we consider the brain as a complex dynamic system and define two measures of brain dynamics: the synchrony of brain activity, measured by the spatial coherence of the BOLD signal across regions of the brain; and metastability, which we define as the extent to which synchrony varies over time. We investigate the relationship among brain network activity, metastability, and cognitive state in humans, testing the hypothesis that global metastability is "tuned" by network interactions. We study the following two conditions: (1) an attentionally demanding choice reaction time task (CRT); and (2) an unconstrained "rest" state. Functional MRI demonstrated increased synchrony, and decreased metastability was associated with increased activity within the frontoparietal control/dorsal attention network (FPCN/DAN) activity and decreased default mode network (DMN) activity during the CRT compared with rest. Using a computational model of neural dynamics that is constrained by white matter structure to test whether simulated changes in FPCN/DAN and DMN activity produce similar effects, we demonstate that activation of the FPCN/DAN increases global synchrony and decreases metastability. DMN activation had the opposite effects. These results suggest that the balance of activity in the FPCN/DAN and DMN might control global metastability, providing a mechanistic explanation of how attentional state is shifted between an unfocused/exploratory mode characterized by high metastability, and a focused/constrained mode characterized by low metastability.
    The Journal of Neuroscience : The Official Journal of the Society for Neuroscience 01/2014; 34(2):451-461. DOI:10.1523/JNEUROSCI.1853-13.2014 · 6.75 Impact Factor
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    Richard J S Wise, Rodrigo M Braga
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    ABSTRACT: Literacy implies convergence, with heard and read narratives directed from separate sensory pathways towards common linguistic and semantic brain systems - very 'bottom-up'. But we also actively infer, relate, remember, attend and, above all, imagine - very 'top-down'. We comment on an interesting investigation of the listening and reading brain.
    Trends in Cognitive Sciences 11/2013; 18(3). DOI:10.1016/j.tics.2013.11.001 · 21.15 Impact Factor
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    ABSTRACT: Aphasic deficits are usually only interpreted in terms of domain-specific language processes. However, effective human communication and tests that probe this complex cognitive skill are also dependent on domain-general processes. In the clinical context, it is a pragmatic observation that impaired attention and executive functions interfere with the rehabilitation of aphasia. One system that is important in cognitive control is the salience network, which includes dorsal anterior cingulate cortex and adjacent cortex in the superior frontal gyrus (midline frontal cortex). This functional imaging study assessed domain-general activity in the midline frontal cortex, which was remote from the infarct, in relation to performance on a standard test of spoken language in 16 chronic aphasic patients both before and after a rehabilitation programme. During scanning, participants heard simple sentences, with each listening trial followed immediately by a trial in which they repeated back the previous sentence. Listening to sentences in the context of a listen-repeat task was expected to activate regions involved in both language-specific processes (speech perception and comprehension, verbal working memory and pre-articulatory rehearsal) and a number of task-specific processes (including attention to utterances and attempts to overcome pre-response conflict and decision uncertainty during impaired speech perception). To visualize the same system in healthy participants, sentences were presented to them as three-channel noise-vocoded speech, thereby impairing speech perception and assessing whether this evokes domain general cognitive systems. As expected, contrasting the more difficult task of perceiving and preparing to repeat noise-vocoded speech with the same task on clear speech demonstrated increased activity in the midline frontal cortex in the healthy participants. The same region was activated in the aphasic patients as they listened to standard (undistorted) sentences. Using a region of interest defined from the data on the healthy participants, data from the midline frontal cortex was obtained from the patients. Across the group and across different scanning sessions, activity correlated significantly with the patients' communicative abilities. This correlation was not influenced by the sizes of the lesion or the patients' chronological ages. This is the first study that has directly correlated activity in a domain general system, specifically the salience network, with residual language performance in post-stroke aphasia. It provides direct evidence in support of the clinical intuition that domain-general cognitive control is an essential factor contributing to the potential for recovery from aphasic stroke.
    Brain 10/2013; 137(1). DOI:10.1093/brain/awt289 · 10.23 Impact Factor
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    ABSTRACT: Intrinsic connectivity networks (ICNs), such as the default mode, frontoparietal control, and salience networks, provide a useful large-scale description of the functional architecture of the brain. Although ICNs are functionally specialized, the information that they process needs to be integrated for coherent cognition, perception, and behavior. A region capable of performing this integration might be expected to contain traces, or "echoes," of the neural signals from multiple ICNs. Here, using fMRI in humans, we show the existence of specific "transmodal" regions containing echoes of multiple ICNs. These regions include core nodes of the default mode network, as well as multimodal association regions of the temporoparietal and temporo-occipito-parietal junction, right middle frontal gyrus, and dorsal anterior cingulate cortex. In contrast, "unimodal" regions such as the primary sensory and motor cortices show a much more singular pattern of activity, containing traces of few or even single ICNs. The presence of ICN echoes might explain how transmodal regions are involved in multiple different cognitive states. Our results suggest that these transmodal regions have a particular local spatial organization containing topographic maps that relate to multiple ICNs. This makes transmodal regions uniquely placed to be able to mediate the cross talk between the brain's functional networks through local modulation of adjacent regions that communicate with different ICNs.
    The Journal of Neuroscience : The Official Journal of the Society for Neuroscience 08/2013; 33(35):14031-9. DOI:10.1523/JNEUROSCI.0570-13.2013 · 6.75 Impact Factor
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    ABSTRACT: This study tested the efficacy of audio-visual reading training in nine patients with pure alexia, an acquired reading disorder caused by damage to the left ventral occipitotemporal cortex. As well as testing the therapy's impact on reading speed, we investigated the functional reorganization underlying therapy-induced behavioural changes using magnetoencephalography. Reading ability was tested twice before training (t1 and t2) and twice after completion of the 6-week training period (t3 and t4). At t3 there was a significant improvement in word reading speed and reduction of the word length effect for trained words only. Magnetoencephalography at t3 demonstrated significant differences in reading network connectivity for trained and untrained words. The training effects were supported by increased bidirectional connectivity between the left occipital and ventral occipitotemporal perilesional cortex, and increased feedback connectivity from the left inferior frontal gyrus. Conversely, connection strengths between right hemisphere regions became weaker after training.
    Brain 08/2013; 136(Pt 8):2579-91. DOI:10.1093/brain/awt186 · 10.23 Impact Factor
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    ABSTRACT: An anterior pathway, concerned with extracting meaning from sound, has been identified in nonhuman primates. An analogous pathway has been suggested in humans, but controversy exists concerning the degree of lateralization and the precise location where responses to intelligible speech emerge. We have demonstrated that the left anterior superior temporal sulcus (STS) responds preferentially to intelligible speech (Scott SK, Blank CC, Rosen S, Wise RJS. 2000. Identification of a pathway for intelligible speech in the left temporal lobe. Brain. 123:2400-2406.). A functional magnetic resonance imaging study in Cerebral Cortex used equivalent stimuli and univariate and multivariate analyses to argue for the greater importance of bilateral posterior when compared with the left anterior STS in responding to intelligible speech (Okada K, Rong F, Venezia J, Matchin W, Hsieh IH, Saberi K, Serences JT,Hickok G. 2010. Hierarchical organization of human auditory cortex: evidence from acoustic invariance in the response to intelligible speech. 20: 2486-2495.). Here, we also replicate our original study, demonstrating that the left anterior STS exhibits the strongest univariate response and, in decoding using the bilateral temporal cortex, contains the most informative voxels showing an increased response to intelligible speech. In contrast, in classifications using local "searchlights" and a whole brain analysis, we find greater classification accuracy in posterior rather than anterior temporal regions. Thus, we show that the precise nature of the multivariate analysis used will emphasize different response profiles associated with complex sound to speech processing.
    Cerebral Cortex 04/2013; 24(9). DOI:10.1093/cercor/bht083 · 8.31 Impact Factor
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    ABSTRACT: A central question for cognitive neuroscience is whether there is a single neural system controlling the allocation of attention. A dorsal frontoparietal network of brain regions is often proposed as a mediator of top-down attention to all sensory inputs. We used functional magnetic resonance imaging in humans to show that the cortical networks supporting top-down attention are in fact modality-specific, with distinct superior fronto-parietal and fronto-temporal networks for visuospatial and non-spatial auditory attention respectively. In contrast, parts of the right middle and inferior frontal gyri showed a common response to attentional control regardless of modality, providing evidence that the amodal component of attention is restricted to the anterior cortex.
    NeuroImage 02/2013; 74(100). DOI:10.1016/j.neuroimage.2013.02.023 · 6.13 Impact Factor
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    ABSTRACT: OBJECTIVE: Episodic memory encoding of a verbal message depends upon initial registration, which requires sustained auditory attention followed by deep semantic processing of the message. Motivated by previous data demonstrating modulation of auditory cortical activity during sustained attention to auditory stimuli, we investigated the response of the human auditory cortex during encoding of sentences to episodic memory. Subsequently, we investigated this response in patients with mild cognitive impairment (MCI) and probable Alzheimer's disease (pAD). METHODS: Using functional magnetic resonance imaging, 31 healthy participants were studied. The response in 18 MCI and 18 pAD patients was then determined, and compared to 18 matched healthy controls. Subjects heard factual sentences, and subsequent retrieval performance indicated successful registration and episodic encoding. RESULTS: The healthy subjects demonstrated that suppression of auditory cortical responses was related to greater success in encoding heard sentences; and that this was also associated with greater activity in the semantic system. In contrast, there was reduced auditory cortical suppression in patients with MCI, and absence of suppression in pAD. Administration of a central cholinesterase inhibitor (ChI) partially restored the suppression in patients with pAD, and this was associated with an improvement in verbal memory. INTERPRETATION: Verbal episodic memory impairment in AD is associated with altered auditory cortical function, reversible with a ChI. Although these results may indicate the direct influence of pathology in auditory cortex, they are also likely to indicate a partially reversible impairment of feedback from neocortical systems responsible for sustained attention and semantic processing. ANN NEUROL 2012.
    Annals of Neurology 02/2013; 73(2). DOI:10.1002/ana.23789 · 11.91 Impact Factor
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    Zarinah K Agnew, Richard J S Wise, Robert Leech
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    ABSTRACT: Mirror neurons are single cells found in macaque premotor and parietal cortices that are active during action execution and observation. In non-human primates, mirror neurons have only been found in relation to object-directed movements or communicative gestures, as non-object directed actions of the upper limb are not well characterized in non-human primates. Mirror neurons provide important evidence for motor simulation theories of cognition, sometimes referred to as the direct matching hypothesis, which propose that observed actions are mapped onto associated motor schemata in a direct and automatic manner. This study, for the first time, directly compares mirror responses, defined as the overlap between action execution and observation, during object directed and meaningless non-object directed actions. We present functional MRI data that demonstrate a clear dissociation between object directed and non-object directed actions within the human mirror system. A premotor and parietal network was preferentially active during object directed actions, whether observed or executed. Moreover, we report spatially correlated activity across multiple voxels for observation and execution of an object directed action. In contrast to predictions made by motor simulation theory, no similar activity was observed for non-object directed actions. These data demonstrate that object directed and meaningless non-object directed actions are subserved by different neuronal networks and that the human mirror response is significantly greater for object directed actions. These data have important implications for understanding the human mirror system and for simulation theories of motor cognition. Subsequent theories of motor simulation must account for these differences, possibly by acknowledging the role of experience in modulating the mirror response.
    PLoS ONE 04/2012; 7(4):e32517. DOI:10.1371/journal.pone.0032517 · 3.53 Impact Factor
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    ABSTRACT: This functional MRI study investigated the involvement of the left inferior parietal cortex (IPC) in spoken language production (Speech). Its role has been apparent in some studies but not others, and is not convincingly supported by clinical studies as they rarely include cases with lesions confined to the parietal lobe. We compared Speech with non-communicative repetitive tongue movements (Tongue). The data were analyzed with both univariate contrasts between conditions and probabilistic independent component analysis (ICA). The former indicated decreased activity of left IPC during Speech relative to Tongue. However, the ICA revealed a Speech component in which there was correlated activity between left IPC, frontal and temporal cortices known to be involved in language. Therefore, although net synaptic activity throughout the left IPC may not increase above baseline conditions during Speech, one or more local systems within this region are involved, evidenced by the correlated activity with other language regions.
    Brain and Language 02/2012; 121(1):47-57. DOI:10.1016/j.bandl.2012.02.005 · 3.31 Impact Factor

Publication Stats

14k Citations
1,214.92 Total Impact Points

Institutions

  • 1999–2015
    • Imperial College London
      • • Division of Brain Sciences
      • • Division of Experimental Medicine
      • • Department of Imaging Sciences
      • • MRC Clinical Sciences Centre
      Londinium, England, United Kingdom
  • 2001–2011
    • MRC Clinical Sciences Centre
      London Borough of Harrow, England, United Kingdom
    • Newcastle University
      Newcastle-on-Tyne, England, United Kingdom
    • University of Bristol
      Bristol, England, United Kingdom
  • 2004–2009
    • University College London
      • Institute of Cognitive Neuroscience
      London, ENG, United Kingdom
  • 1983–2009
    • Ealing, Hammersmith & West London College
      Londinium, England, United Kingdom
  • 2001–2006
    • Oxford University Hospitals NHS Trust
      • Department of Clinical Neurology
      Oxford, England, United Kingdom
  • 2004–2005
    • University of Oxford
      • Nuffield Department of Clinical Neurosciences
      Oxford, England, United Kingdom
  • 2000
    • MRC Cognition and Brain Sciences Unit
      Cambridge, England, United Kingdom
  • 1997
    • University of Birmingham
      Birmingham, England, United Kingdom
  • 1996
    • University of Cambridge
      Cambridge, England, United Kingdom
  • 1995
    • Birkbeck, University of London
      Londinium, England, United Kingdom
  • 1993
    • London School of Hygiene and Tropical Medicine
      Londinium, England, United Kingdom
  • 1991
    • Tel Aviv University
      Tell Afif, Tel Aviv, Israel
    • Medical Research Council (UK)
      Londinium, England, United Kingdom