J.A. Gray

King's College London, London, ENG, United Kingdom

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Publications (150)624.66 Total impact

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    ABSTRACT: There is an increasing body of evidence pointing to a neurobiological basis of personality. The purpose of this study was to investigate the biological bases of the major dimensions of Eysenck's and Cloninger's models of personality using a noninvasive magnetic resonance perfusion imaging technique in 30 young, healthy subjects. An unbiased voxel-based analysis was used to identify regions where the regional perfusion demonstrated significant correlation with any of the personality dimensions. Highly significant positive correlations emerged between extraversion and perfusion in the basal ganglia, thalamus, inferior frontal gyrus and cerebellum and between novelty seeking and perfusion in the cerebellum, cuneus and thalamus. Strong negative correlations emerged between psychoticism and perfusion in the basal ganglia and thalamus and between harm avoidance and perfusion in the cerebellar vermis, cuneus and inferior frontal gyrus. These observations suggest that personality traits are strongly associated with resting cerebral perfusion in a variety of cortical and subcortical regions and provide further evidence for the hypothesized neurobiological basis of personality. These results may also have important implications for functional neuroimaging studies, which typically rely on the modulation of cerebral hemodynamics for detection of task-induced activation since personality effects may influence the intersubject variability for both task-related activity and resting cerebral perfusion. This technique also offers a novel approach for the exploration of the neurobiological correlates of human personality.
    No preview · Article · Jul 2006 · NeuroImage
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    ABSTRACT: The amplitude of the startle reflex response is known to be influenced by the concomitant presentation of affect-toned material--if it is positive affect-toned, the reflex is inhibited, and if it is negative affect-toned, the reflex is augmented. Abundant evidence demonstrates the utility of the affect-startle paradigm as a significant tool for measuring both positive and negative emotions. We applied this paradigm to study emotional reactivity in depression, particularly in relation to symptoms of depression, anhedonia, and anxiety. Depressed patients (22) and controls (22) were shown a series of film clips, consisting of two clips with positive valence, two with negative valence, and two with relatively neutral valence. The startle response was measured in reaction to the acoustic startle-eliciting stimuli presented three times binaurally during each clip. Highly depressed and anhedonic patients, relative to controls, showed a reduced mood (self-ratings) and a lack of startle modulation in response to affective film clips whereas patients relatively low on depression/anhedonia displayed a reduced mood only with pleasant clips and a normal pattern of affective startle modulation. Anhedonia and depression were highly positively correlated but neither correlated with anxiety. Anxious patients displayed larger reflexes across all clips and showed a reduced mood modulation with pleasant, but not unpleasant, clips. The large majority of patients was medicated with antidepressants which may have influenced the results. CONCLUSIONS. Reactivity to pleasant stimuli is diminished in patients suffering from low levels of depression and/or anhedonia, but reactivity even to unpleasant stimuli seems compromised at high levels of depression and/or anhedonia. Anxiety is associated with hyperstartle responding.
    Full-text · Article · Dec 2004 · Journal of Affective Disorders
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    ABSTRACT: Clozapine-like atypical antipsychotic drugs, such as olanzapine, risperidone and sertindole, bind most strongly to 5-HT(2A) receptors, which may contribute to their antipsychotic effects. Antipsychotic drugs, such as clozapine and haloperidol, have been found to enhance latent inhibition (LI) in humans and rats. LI is a process of learning to ignore irrelevant stimuli that is disrupted in acute, positive-symptom schizophrenia, and can be modelled in animals. The aim of this study was to determine the effects of two selective 5-HT(2A) receptor antagonists, SR 46,349B and ICI 169,369, on LI, as a test of their antipsychotic potential. Doses of the 5-HT(2A) receptor antagonists that were sufficient for receptor blockade were determined in 5-HT behavioural syndrome tests. SR 46,349B and ICI 169,369 were then tested for enhancement of LI and reversal of amphetamine-induced attenuation of LI in a conditioned suppression paradigm. SR 46,349B (0.6-2.4 mg kg(-1) i.p.) and ICI 169,369 (10-40 mg kg(-1) i.p.) antagonised 5-hydroxytryptophan (5-HTP)-induced head twitches and wet dog shakes, which are mediated by 5-HT(2A) receptors, but had no effect on mCPP-induced hypolocomotion, which is mediated by 5-HT(2C) receptors. Neither SR 46,349B (1.2 mg kg(-1) i.p.) nor ICI 169,369 (40 mg kg(-1) i.p) affected 8-hydroxy-2-(di- n-propylamino)tetralin (8-OH-DPAT)-induced forepaw treading, suggesting that they were not in vivo 5-HT(1A) receptor antagonists. SR 46,349B (2.4 mg kg(-1) i.p.) and ICI 169,369 (40 mg kg(-1) i.p.) enhanced LI when given at both the pre-exposure and conditioning stages of the paradigm, but not when given at either pre-exposure or conditioning only. Both drugs also reversed the disruption of LI induced by D-amphetamine (1 mg kg(-1) i.p.). The profile of SR 46,349B and ICI 169,369 in LI differs from that of clozapine and haloperidol in LI, which both enhance LI when given only at the conditioning stage of the paradigm.
    No preview · Article · Oct 2003 · Psychopharmacology
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    ABSTRACT: Latent inhibition describes a process of learning to ignore stimuli of no consequence, and is disrupted in acute, positive-symptomatic schizophrenia. Understanding the neural basis of latent inhibition in animals may help to elucidate the neural dysfunction underlying positive schizophrenic symptoms in man. Evidence suggests a crucial role for dopamine transmission in the nucleus accumbens in the control of latent inhibition. The present studies investigated the role of the GABA-ergic efferent from the nucleus accumbens to the ventral pallidum in latent inhibition. The GABA(A) agonist muscimol (4.56 ng/microl), and antagonist picrotoxin (0.2 microg/microl), were infused into the ventral pallidum, and effects on latent inhibition were assessed using a conditioned suppression procedure. Neither drug produced specific effects on latent inhibition when given alone and, in the case of muscimol, failed to reverse the disruption of latent inhibition induced by systemic amphetamine. In addition to significant non-specific drug effects, a positive control experiment revealed that intra-pallidal picrotoxin significantly enhanced locomotion, suggesting that our manipulations of ventral pallidal GABA function were behaviourally effective. We conclude that modulating ventral pallidal GABA transmission does not affect latent inhibition. The implications of this finding for theories of the neural circuitry mediating latent inhibition and for understanding the functional role of ventral pallidal GABA transmission are discussed.
    No preview · Article · Feb 2003 · Neuroscience
  • K P Datla · R G Ahier · A M J Young · J A Gray · M H Joseph
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    ABSTRACT: This study used in vivo microdialysis to examine the release of dopamine (DA) in the nucleus accumbens (nAc) during the performance of a previously learned, signalled sucrose reward task, and during conditioning of a neutral tone stimulus to this reward. Behavioural measures (magazine entries) confirmed that stimuli associated with sucrose presentation became secondary rewarding stimuli, and DA release was also monitored during subsequent presentation of these stimuli alone. Perhaps surprisingly, during magazine entry for consumption of sucrose, i.e. in conditions similar to routine training, dialysate DA levels in the nAc did not increase. In contrast, during conditioning of the tone with light-sucrose, dopamine levels increased consistently and significantly. Interestingly, DA levels were somewhat, but significantly, increased when tone alone was presented in a test session, i.e. two hours after conditioning, and even more so when tone was combined with the light previously associated with sucrose. In this latter case the number of magazine entries increased to a level similar to that seen during conditioning. Presentation of light alone resulted in a similar level of magazine entries to tone alone, but no significant increase in DA. In summary, these studies confirm that a neutral stimulus can acquire the behavioural properties of reward when conditioned. The neurochemical data, on the other hand, suggest that increases of DA in nAc are more likely to be related to new associative learning than to established incentive or consumatory processes. The increase in DA release in the test session may be related either to the secondary reinforcing properties acquired by the stimulus, or to the change in contingencies, or to the aversive effects of the omission of reward.
    No preview · Article · Dec 2002 · European Journal of Neuroscience
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    ABSTRACT: Latent inhibition (LI) is a model of attention, which is a cognitive process that can be modulated by stressors such as chronic intermittent broadband noise, e.g. caused by building work, which is particularly stressful to rats. The aim of this study was to analyse the effect of chronic noise stress, caused by a building project, on LI, and its interaction with SR 46,349B, a 5-HT2A receptor antagonist. Control groups from LI experiments conducted during periods of chronic intermittent noise were compared with control groups from LI experiments conducted in normal quiet conditions. The interaction of SR 46,349B with the effects of chronic noise stress was then tested. Chronic intermittent noise attenuated LI, an effect which was partially reversed by SR 46,349B, 2.4 mg/kg i.p. Attenuation of LI by chronic intermittent noise and reversal of this effect by SR 46,349B support suggestions that stress can modulate attention and that 5-HT2A receptors are involved in mediating the effects of chronic stress.
    No preview · Article · Nov 2002 · Behavioural Pharmacology
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    ABSTRACT: In 'colored-hearing' synesthesia, individuals report color experiences when they hear spoken words. If the synesthetic color experience resembles that of normal color perception, one would predict activation of parts of the visual system specialized for such perception, namely the human 'color center', referred to as either V4 or V8. Using functional magnetic resonance imaging (fMRI), we here locate the region activated by speech in synesthetes to area V4/V8 in the left hemisphere, and demonstrate overlap with V4/V8 activation in normal controls in response to color. No activity was detected in areas V1 or V2, suggesting that activity in primary visual cortex is not necessary for such experience. Control subjects showed no activity in V4/V8 when imagining colors in response to spoken words, despite overtraining on word-color associations similar to those spontaneously reported by synesthetes.
    Full-text · Article · May 2002 · Nature Neuroscience
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    ABSTRACT: Functionalism offers an account of the relations that hold between behavioural functions, information and neural processing, and conscious experience from which one can draw two inferences: (1) for any discriminable difference between qualia there must be an equivalent discriminable difference in function; and (2) for any discriminable functional difference within a behavioural domain associated with qualia, there must be a discriminable difference between qualia. The phenomenon of coloured hearing synaesthesia (in which individuals see colours when they hear or see words) appears to contradict the second of these inferences. We report data showing that this form of synaesthesia is genuine and probably results from an aberrant projection from cortical language areas to a region (V4/V8) specialized for the perception of colour. Since functionalism purports to be a general account of consciousness, one such negative instance, if it can be further sustained empirically, is sufficient to invalidate it.
    No preview · Article · Dec 2001 · Journal of Consciousness Studies
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    ABSTRACT: Many theoretical accounts of selective attention and memory retrieval include reference to active inhibitory processes, such as those argued to underlie the negative priming effect. fMRI was used in order to investigate the areas of cortical activation associated with Stroop interference, Stroop facilitation and Stroop negative priming tasks. The most significant activation within the negative priming task was within the inferior parietal lobule, left temporal lobe and frontal lobes. Areas of cortical activation are discussed with reference to theoretical accounts of the negative priming effect.
    Full-text · Article · Dec 2001 · Neuroreport
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    ABSTRACT: Early neuropathology following a prolonged duration of four-vessel occlusion (4 VO) ischemia in the rat was charted using magnetic resonance imaging (MRI). Animals received either 30 minutes of 4 VO (N = 6) or sham operation (N = 6) prior to in vivo assessment. Proton density and T(2) and combined T(2)/diffusion-weighted (T(2)/DW) MRI were performed at 6, 24, and 72 hours postocclusion. T(2)/DW imaging was the most effective sequence for delineating between injured and intact tissues, indicating neuropathology in the dorsolateral striatum at 24 hours and in the CA1/CA2 subfields of the hippocampus at 72 hours following ischemia. Apparent diffusion coefficient values were significantly reduced in the striatum (P = 0.03) and hippocampus (P = 0.005) at 24 and 72 hours, respectively. This is the first report, to our knowledge, of T(2)/DW imaging detecting lesions following 4 VO in accord with the known temporal evolution of ischemic brain damage.
    No preview · Article · Sep 2001 · Journal of Magnetic Resonance Imaging

  • No preview · Article · Jun 2001 · NeuroImage
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    ABSTRACT: Despite the many studies highlighting the role of the amygdala in fear perception, few have examined differences between right and left amygdalar responses. Using functional magnetic resonance imaging (fMRI), we examined neural responses in three groups of healthy volunteers (n = 18) to alternating blocks of fearful and neutral faces. Initial observation of extracted time series of both amygdalae to these stimuli indicated more rapid decreases of right than left amygdalar responses to fearful faces, and increasing magnitudes of right amygdalar responses to neutral faces with time. We compared right and left responses statistically by modeling each time series with (1) a stationary fit model (assuming a constant magnitude of amygdalar response to consecutive blocks of fearful faces) and (2) an adaptive model (no assumptions). Areas of significant sustained nonstationarity (time series points with significantly greater adaptive than stationary model fits) were demonstrated for both amygdalae. There was more significant nonstationarity of right than left amygdalar responses to neutral, and left than right amygdalar responses to fearful faces. These findings indicate significant variability over time of both right and left amygdalar responses to fearful and neutral facial expressions and are the first demonstration of specific differences in time courses of right and left amygdalar responses to these stimuli.
    Full-text · Article · May 2001 · Human Brain Mapping
  • A.Martins Serra · S H Jones · B Toone · JA Gray
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    ABSTRACT: The performance of chronic schizophrenic probands (n=21), their first-degree schizotypal (22) and non-schizotypal (19) relatives, and normal controls (24), was measured in two associative learning paradigms, latent inhibition and the Kamin blocking effect. These paradigms assess the effects on learning of initial exposure to other learning contingencies. The normal subjects showed latent inhibition (retarded learning of an association between a burst of white noise and a visually displayed counter increment, if the subject had first been pre-exposed to the white noise without any other consequence) and Kamin blocking (retarded learning of an association between two visual stimuli, if the conditioned stimulus was presented simultaneously with a second, already conditioned stimulus). The schizophrenic probands and both the schizotypal and non-schizotypal relatives were severely impaired in basic associative learning, performing much worse than the normal subjects in the control conditions (i.e. those lacking stimulus pre-exposure of any kind) of both the latent inhibition and the Kamin paradigms and also showed a loss of the normal latent inhibition and Kamin blocking effects. The performance of the three clinically defined groups was statistically indistinguishable. These findings contrast with previous reports of the performance of normal subjects classified as schizotypal by questionnaire, who are not impaired in basic associative learning, and are particularly fast to learn after stimulus pre-exposure. The results question the assumption that high schizotypy, as assessed by questionnaire, is like schizotypy in schizophrenic kin. The severe impairment in basic associative learning in schizophrenic patients and their kin warrants further investigation.
    No preview · Article · Apr 2001 · Schizophrenia Research

  • No preview · Article · Sep 2000 · European Neuropsychopharmacology

  • No preview · Article · May 2000 · NeuroImage

  • No preview · Article · Apr 2000 · Biological Psychiatry
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    ABSTRACT: Experiments are described using rats with two kinds of brain damage and consequent cognitive deficit (in the Morris water maze, three-door runway, and radial maze): 1) ischemic damage to the CA1 hippocampal cell field after four-vessel occlusion (4VO), and 2) damage to the forebrain cholinergic projection system by local injection of excitotoxins to the nuclei of origin or prolonged ethanol administration. Cell suspension grafts derived from primary fetal brain tissue display a stringent requirement for homotypical cell replacement in the 4VO model: cells from the embryonic day (E)18-19 CA1 hippocampal subfield, but not from CA3 or dentate gyrus or from E16 basal forebrain (cholinergic rich) led to recovery of cognitive function. After damage to the cholinergic system, conversely, recovery of function was seen with cell suspension grafts from E16 basal forebrain or cholinergic-rich E14 ventral mesencephalon, but not with implants of hippocampal tissue. These two models therefore provided a test of multifunctionality for a clonal line of conditionally immortalized neural stem cells, MHP36, derived from the E14 "immortomouse" hippocampal anlage. Implanted above the damaged CA1 cell field in 4VO-treated adult rats, these cells (multipotential in vitro) migrated to the damaged area, reconstituted the gross morphology of the CA1 pyramidal layer, took up both neuronal and glial phenotypes, and gave rise to cognitive recovery. Similar recovery of function and restoration of species-typical morphology was observed when MHP36 cells were implanted into marmosets with excitotoxic CAI damage. MHP36 implants led to recovery of cognitive function also in two experiments with rats with excitotoxic damage to the cholinergic system damage, either unilaterally in the nucleus basalis or bilaterally in both the nucleus basalis and the medial septal area. Thus, MHP36 cells are both multipotent (able to take up multiple cellular phenotypes) and multifunctional (able to repair diverse types of brain damage).
    No preview · Article · Mar 2000 · Cell Transplantation
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    ABSTRACT: Late fetal CA1 hippocampal grafts and stem cell grafts from the conditionally immortal MHP36 clonal line derived from the H-2Kb-tsA58 transgenic mouse neuroepithelium both improved spatial deficits in rats with ischaemic CA1 damage induced by four-vessel occlusion (4VO). However, the distribution of fetal and MHP36 grafts differed. Fetal cells lodged in clumps around the implant sites and along the corpus callosum, whilst MHP36 grafts infiltrated the area of CA1 ischaemic damage, achieving apparent architectural reconstruction of the hippocampus. The migration of MHP36 cells is damage-dependent. Few cells were found in intact brain; after 15 min of 4VO cells repopulated only the discrete area of CA1 cell loss, whereas with more extensive damage after 30 min occlusion cells migrated to all hippocampal fields and to cortex. A higher proportion of grafted MHP36 cells differentiated into neurons in the host CA1 field than grafts of striatal or cortical expanded cell populations. Cortical population grafts were as effective as MHP36 grafts in improving water maze learning, whereas striatal or ventral mesencephalic cells were ineffective, indicating a degree of stem cell specificity. The efficacy of MHP36 cells extends to primates. In marmosets with profound impairments in conditional discrimination tasks after lesions of the CA1 field, MHP36 cells improved performance as effectively as fetal grafts and migrated evenly through the CA1 field, in contrast to clustered fetal cells. These findings suggest that MHP36 stem cell grafts are as effective as fetal grafts in functional repair of hippocampal damage, and that their preference for areas of cell loss and adoption of appropriate morphologies is consistent with a point-to-point repair mechanism.
    No preview · Article · Feb 2000 · Novartis Foundation symposium
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    ABSTRACT: In order to investigate the effects of stem cell grafts on water maze deficits in aged (22-month-old) rats, three groups of aged rats, assigned by pre-training latency scores to unimpaired, impaired control and impaired grafted groups, were compared with young (five-month-old) controls, six to eight weeks after implantation of cells from the conditionally immortal Maudsley hippocampal stem cell line, clone 36 (MHP36 stem cell line), in the cortex, striatum and hippocampus. Grafted rats were substantially superior to their matched impaired aged controls, and learned to find the platform as rapidly as unimpaired aged rats, although young controls were more efficient than all aged groups in several measures of spatial search during training. On the probe trial, however, aged rats with grafts showed significantly better recall of the precise position of the platform than any other group, including young controls, possibly indicating some perseveration. A further comparison found that groups of unimpaired and moderately impaired aged rats showed far less improvement from water maze pre-training to acquisition phases than young controls, indicative of progressive deficits over time. Histological investigation showed that beta-galactosidase-positive MHP36 cells migrated widely from the implantation sites to infiltrate the striatal matrix, all hippocampal fields and areas of the cortex. Grafted cells showed both astrocytic and neuronal morphologies, with cells of pyramidal and granular appearance in appropriate hippocampal strata.Taken together, these results indicate that neuroepithelial stem cell grafts extensively colonize the aged rat brain and substantially reverse progressive cognitive decline associated with ageing.
    Full-text · Article · Feb 2000 · Neuroscience
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    ABSTRACT: Purpose: Loss of cholinergic projections from the basal forebrain (BF) to the cortex and from the medial septal area (MSA) to tbe hippocampus is a reliable correlate of cognitive deficits in aging and Alzheimer's disease (AD). We assessed the capacity of grafts of the conditionally immortal MHP36 clonal stem cell line to improve spatial learning in rats showing profound deficits after lesions to these projections. Methods: Rats were lesioned by infusions of S-AMPA unilaterally into BF or bilaterally into both BF and MSA. MHP36 cells were implanted ipsilaterally in cortex or basal forebrain two weeks after unilateral BF lesions, and in cortex and hippocampus bilaterally six months after bilateral BF-MSA lesions. Intact and lesion-only controls received vehicle. Six weeks later rats were assessed in spatial learning and memory tasks in the water maze, and then perfused for identification of grafted cells by beta-galactosidase immunohistocheniistry. Results: Lesioned rats with MHP36 grafts, whether implanted two weeks or six months after lesioning, learned to find a submerged platform in the water maze as rapidly as intact controls, and showed a strong preference for the platform quadrant on probe trials, whereas lesioned controls were impaired in all measures. Grafted cells of both neuronal and glial morphologies, migrated away from cortical implantation sites in BF Lesioned rats to the striatum, thalamus and basal forebrain lesion area. Cells implanted in basal forebrain showed a similar distribution. In rats with bilateral BF-MSA lesions, grafts implanted in the hippocampus migrated widely through all layers but cortical grafts largely escaped up the needle tract into the meninges. Conclusions: Although MHP36 grafts were functionally effective in both lesion models, the site and age of lesions and site of implantation influenced the pattern of engraftment. This flexibility encourages the development of conditionally immortal human stem cell lines with similar capacities for functional repair of variable neuronal degeneration in AD or aging.
    No preview · Article · Feb 2000 · Restorative neurology and neuroscience

Publication Stats

9k Citations
624.66 Total Impact Points


  • 2000-2006
    • King's College London
      • • Department of Psychology
      • • Institute of Psychiatry
      London, ENG, United Kingdom
    • Reneuron
      Guilford, England, United Kingdom
  • 2002
    • Goldsmiths, University of London
      • Department of Psychology
      Londinium, England, United Kingdom
  • 1998
    • The Peninsula College of Medicine and Dentistry
      Plymouth, England, United Kingdom
  • 1984-1998
    • University of London
      Londinium, England, United Kingdom
  • 1997
    • University of Leicester
      Leiscester, England, United Kingdom
  • 1976-1993
    • University of Oxford
      • Department of Experimental Psychology
      Oxford, England, United Kingdom
  • 1992
    • New South Wales Institute of Psychiatry
      Sydney, New South Wales, Australia
  • 1980
    • University of Cambridge
      Cambridge, England, United Kingdom