M E Corcoran

University of Victoria, Victoria, British Columbia, Canada

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Publications (79)256.49 Total impact

  • T H Gilbert, R K McNamara, M E Corcoran
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    ABSTRACT: We used two procedures to assess the spatial learning and memory of rats in the Morris water maze task subsequent to kindling of hippocampal field CA1: (1) seizures were kindled with stimulation of CA1 prior to training in the water maze (acquisition); and (2) maze training was imposed until performance stabilized, seizures were kindled with stimulation of CA1, and then performance in the maze was reassessed (retention). In both conditions, behavioral testing occurred 24 h after the last kindled seizure. When the effects of CA1 kindling on acquisition were tested, we found that kindling of generalized seizures with stimulation of field CA1 (kindling), but not kindling of non-convulsive or partial seizures (partial kindling), produced deficits in the water maze. When the effects of CA1 kindling on retention were tested, however, we found that kindling of either partial or generalized seizures produced deficits in the water maze. The results suggest that the processing of spatial information is vulnerable to the long-lasting changes in neural excitability associated with kindling.
    Behavioural Brain Research 01/1997; 82(1):57-66. · 3.33 Impact Factor
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    ABSTRACT: Alternating stimulation of two sites in the forebrain culminates in typical kindling of generalized seizures from one site (dominant), whereas the other site (suppressed) supports only nongeneralized seizures for as long as stimulation of the dominant site continues, a phenomenon referred to as kindling antagonism. With the termination of stimulation of the dominant site, however, seizures provoked from the suppressed site eventually generalize, a progression thought to reflect the resumption of kindling from a previous point of arrest. To further assess the nature of kindling antagonism, we established antagonism between the amygdala and the septal area and subsequently evaluated the development of seizures provoked by stimulation of sites distal to the dominant site (always the amygdala). In Experiment 1, a 30-d stimulation-free period imposed after the establishment of antagonism failed to result in immediate generalization of seizures provoked from the suppressed site (septal area) in seven of eight rats. Although these results suggest that antagonism reflects an actual arrest of kindling rather than a transient inhibition of seizures, they are not entirely unambiguous: Rats exposed to the prolonged stimulation-free period required only half the number of septal stimulations for the expression of a generalized seizure as compared to rats receiving septal stimulation immediately after the establishment of antagonism. The latter finding is suggestive of a transient component of antagonism. In Experiment 2, development of generalized seizures from the previously naive right amygdala was virtually identical in rats previously kindled from the left amygdala and in rats expressing antagonism between the septal area and left amygdala. Development of generalized seizures from the right amygdala was faster than from the left amygdala in both groups of rats, however, suggesting that the expression of seizures provoked from the suppressed site after the establishment of antagonism does not involve a general impairment or enhancement of transfer. Experiment 3 revealed that radio-frequency lesions of the dominant site (amygdala) after the establishment of antagonism did not alter the subsequent development of generalized seizures from the suppressed site (septal area). This suggests that the expression of generalized seizures from the suppressed site after the establishment of kindling antagonism is not dictated by the functional state of the dominant site.
    Epilepsy Research 07/1995; 21(2):115-24. · 2.24 Impact Factor
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    ABSTRACT: Previous experiments have described highly specific effects of noradrenergic agonists on synaptic transmission in the dentate gyrus (DG). For example, perfusion of hippocampal slices with the beta-noradrenergic agonist isoproterenol induces a long-lasting potentiation (LLP) of extracellularly recorded responses following stimulation of the medial perforant path (PP), and long-lasting depression (LLD) of responses evoked by stimulation of the lateral PP (Dahl D, Sarvey JM, 1989, Proc Natl Acad Sci USA 86:4776-4780). To examine the possible interactions of LLP, LLD, and long-term potentiation induced by tetanic stimulation (LTP), the authors recorded extracellular field potentials evoked in the DG by stimulation of the lateral or medial perforant path following LTP and LLP or LLD, invoked in different orders. After establishment of LLP or LLD by bath application of isoproterenol, subsequent tetanization of the respective afferents resulted in additional potentiation of the medial PP-evoked response and return of the lateral PP-evoked response to baseline levels. In other slices, application of isoproterenol after establishment of LTP resulted in further potentiation of medial PP-evoked responses but no change in the potentiated response evoked by lateral PP stimulation. Thus the pathway specificity was maintained irrespective of the history of previous potentiation or depression. Experiments using the specific beta 1 antagonist metoprolol further confirmed pathway specificity. Perfusion with 20 microM of metoprolol appeared to reduce LTP evoked by stimulation of the medial but not lateral PP. In a subsequent experiment, metoprolol in the absence of tetanization produced LLD of the medial PP-evoked response and LLP of the lateral PP-evoked response, opposite to the effects of ISO.(ABSTRACT TRUNCATED AT 250 WORDS)
    Hippocampus 05/1994; 4(2):181-8. · 5.49 Impact Factor
  • M R Pelletier, M E Corcoran
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    ABSTRACT: We reported previously that activation of alpha-2 adrenoceptors with infusions of clonidine into the amygdala/pyriform region is sufficient to retard kindling. To characterize further the involvement in kindling of alpha-2 receptors in the amygdala/pyriform, we exposed rats to unilateral intraamygdaloid infusions of a variety of noradrenergic drugs followed by either low-frequency stimulation of the amygdala, to induce rapid kindling, or conventional high-frequency stimulation. Infusions and electrical stimulation were administered once every 48 h. The prophylactic effects of clonidine were blocked by simultaneous infusion of idazoxan, an alpha-2 adrenergic antagonist, which suggests strongly that these effects were produced at an alpha-2 receptor. Intraamygdaloid infusions of xylazine, another alpha-2 agonist, also significantly retarded low-frequency kindling. Unexpectedly, intraamygdaloid infusions of the alpha-2 antagonists idazoxan, yohimbine, and SK&F 104856 failed to accelerate kindling. Infusion of the alpha-1 antagonist corynanthine also failed to affect kindling. We propose that the alpha-2 adrenoceptors in the amygdala/pyriform region contribute to the prophylactic effects of systemically administered clonidine and that the facilitation of kindling observed after systemic administration of alpha-2 antagonists may be due to blockade of alpha-2 adrenoceptors outside of the amygdala/pyriform region.
    Brain Research 12/1993; 632(1-2):29-35. · 2.88 Impact Factor
  • R K McNamara, M E Corcoran
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    ABSTRACT: To clarify the role of benzodiazepine receptors in kindling, the present experiment assessed the effects of CL 218,872 (1, 5, 10, and 20 mg/kg), a triazolopyridazine with a selective affinity for the putative benzodiazepine BZ1 receptor subtype, on the development and expression of amygdaloid-kindled seizures. Additionally, we assessed the effects of flumazenil (10 mg/kg), a non-specific benzodiazepine receptor antagonist, on kindling and the expression of kindled seizures alone or concomitantly with CL 218,872 (20 mg/kg). CL 218,872 retarded the development of kindled seizures in a linear dose-dependent manner; rats treated with 5, 10, and 20 mg/kg, but not 1 mg/kg, of CL 218,872 required a greater number of afterdischarges (ADs) to develop generalized seizures than controls. Flumazenil also retarded kindling and failed to attenuate the prophylactic effect of CL 218,872. In a cross-over procedure rats that did not develop generalized seizures after 30 ADs while under drug were rekindled under vehicle and rats kindled under vehicle were subsequently tested under drug. Rats crossed over to vehicle rekindled at a faster rate than did controls during initial kindling, suggesting that some kindling had occurred under the drug. CL 218,872 also dose-dependently depressed kindled seizures and this was attenuated by flumazenil, which had little effect on kindled seizures by itself. Together, these data suggest that CL 218,872 is a potent anticonvulsant, implicating the BZ1 receptor subtype in seizure development and in the expression of kindled seizures.
    Epilepsy Research 10/1993; 16(1):19-26. · 2.24 Impact Factor
  • R D Kirkby, T H Gilbert, M E Corcoran
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    ABSTRACT: Previous research has shown that concurrent alternating stimulation of paired limbic sites culminates in kindling of generalized seizures from 1 (dominant) site, whereas the other (suppressed) site supports only focal or partial seizures. This phenomenon has been referred to as kindling antagonism, and it has been proposed that antagonism reflects an arrest of kindling, which is therefore viewed as a non-continuous stepwise process. We have attempted to replicate these important observations in adult rats stimulated in various combinations of forebrain sites. Kindling antagonism was displayed by rats stimulated in the amygdala and the septal area, in the bilateral amygdala, the septal area and the splenium of the corpus callosum, and the amygdala and the cingulate cortex. We also found that antagonism between the amygdala and septal area as well as electrographic and behavioral correlates of alternating stimulation were sensitive to the hemispheric relation of the electrodes and to the order in which the sites received initial stimulations. That is, rats that carried ipsilateral amygdaloid and septal electrodes were less likely to display antagonism when the amygdala was the first site stimulated. On the other hand, we failed to obtain antagonism from rats stimulated in other limbic pairs (e.g. entorhinal cortex and septal areas.
    Brain Research 08/1993; 616(1-2):17-24. · 2.88 Impact Factor
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    ABSTRACT: There is some controversy about the role of long-term potentiation (LTP) in spatial learning. The authors have found that triggering generalized kindled seizures with stimulation of the perforant path disrupts spatial learning in the Morris water maze but that kindling per se does not affect spatial learning. It is suggested that abnormal electrical activity induced by high-frequency stimulation of the perforant path may have been responsible for the disruption of spatial learning previously attributed to LTP saturation.
    Hippocampus 05/1993; 3(2):149-52. · 5.49 Impact Factor
  • M R Pelletier, M E Corcoran
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    ABSTRACT: It has been reported previously that systemic administration of clonidine, an agonist of alpha-2 noradrenergic receptors, significantly retards amygdaloid kindling by delaying the emergence from partial seizure. We examined the effect of either systemic administration (i.p.) or intra-amygdaloid infusions of clonidine on the kindling of seizures with electrical stimulation of the amygdala. Rats received either low-frequency stimulation of the amygdala, to induce rapid kindling, or conventional high-frequency stimulation. Clonidine and electrical stimulation were administered once every 48 h. We observed a significant retardation of kindling in rats receiving i.p. injections of clonidine (0.1 mg/kg) or infusions of clonidine in concentrations of 10(-7)-10(-4) M, regardless of the stimulation frequency. The prophylactic effect was due to a delay in the progression out of partial seizure. The effect was specific to the amygdala/pyriform region, because infusions of clonidine dorsal to the amygdala were without effect. Intra-amygdaloid clonidine had little effect on established generalized seizures, suggesting that it was producing a genuine prophylactic effect against kindling. We conclude that the subpopulation of alpha-2 adrenoceptors in the amygdala/pyriform region contributes to the antiepileptogenic effect observed after systemic administration of clonidine.
    Brain Research 01/1993; 598(1-2):51-8. · 2.88 Impact Factor
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    ABSTRACT: We investigated the effects of kindling and kindled seizures in different limbic structures on place and cue learning in the Morris water maze. The triggering of seizures by stimulation of the perforant path, septum, or amygdala prior to daily training impaired place learning, but had little effect on visible platform training or swim speed. Seizures triggered by stimulation of the medial perforant path after daily training also impaired place learning. Conversely, place learning proceeded normally in rats tested 24 h after kindling triggered by stimulation of the perforant path, septum, or amygdala, indicating that kindling per se does not affect place learning. Each group was able to learn the location of a reversed platform when pretraining seizures were discontinued; and perforant path and septal kindled rats, but not amygdaloid kindled rats, were impaired at learning the location of a reversed platform when seizures were triggered before training. The results confirm previous reports that limbic seizures produce amnesia, but they contradict the finding that hippocampal kindling impairs learning on tasks sensitive to hippocampal lesions.
    Behavioural Brain Research 10/1992; 50(1-2):167-75. · 3.33 Impact Factor
  • D P Cain, F Boon, M E Corcoran
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    ABSTRACT: D-Tyr-Ser-Gly-Phe-Leu-Thr (DSLET), beta-endorphin, morphiceptin and morphine were microinjected at 48-h intervals into the amygdala or hippocampus of awake rats in an attempt to identify the opiate receptor types involved in opioid kindling. DSLET, beta-endorphin, morphiceptin and morphine were injected into the lateral ventricle to assess the possibility of kindling seizures by this route. The delta-receptor agonist DSLET effectively kindled convulsions when microinjected into amygdala or ventral hippocampus. The convulsions were suppressed or strongly attenuated by ICI 174,864, a specific antagonist of the delta-receptor, microinjected into the same brain site, but were not affected by ICI 174,864 administered peripherally. When microinjected into amygdala or hippocampus, beta-endorphin and morphiceptin also kindled convulsions, which were antagonized by naloxone but not by ICI 174,864. Morphine evoked EEG epileptiform activity but did not kindle convulsions from limbic brain sites. DSLET occasionally evoked epileptiform spiking and submaximal convulsions when injected into ventricle, and morphiceptin evoked epileptiform spiking only, but tolerance to these effects occurred after repetition of the injections. Thus, convulsions can be kindled by activation of either mu-, delta- or epsilon-receptors when opioids are injected directly into limbic tissue. However, the ability of these compounds to kindle seizures is markedly reduced when they are administered into ventricle. The striking differences between the present results and previous results obtained by peripheral or intraventricular administration of opioid peptides suggest that the route of administration, among other variables, is a crucial factor in assessing the epileptogenic properties of opioid peptides.
    Brain Research 06/1990; 517(1-2):236-44. · 2.88 Impact Factor
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    ABSTRACT: Electrical stimulation of the noradrenergic locus coeruleus (LC) delays the generalization of partial seizures during amygdaloid kindling by increasing the time spent in the earliest stages of seizure development. To determine whether noradrenergic axons projecting to the midbrain and forebrain are involved in this antikindling effect, we examined the effects of lesions of the dorsal noradrenergic bundle, induced by intracerebral infusions of 6-hydroxydopamine (6-OHDA), on kindling and the antikindling action of stimulation of the LC. Stimulation of the LC during amygdaloid kindling increased the number of afterdischarges (ADs) spent in the early stages of partial seizure and decreased the number of ADs spent in later stages of generalized seizure, as has been described previously. LC-stimulated rats also displayed longer durations of AD during early stages of kindling. The antikindling effect of LC stimulation was blocked by lesions of the dorsal bundle, whereas the facilitatory effects of LC stimulation on generalization and on the duration of AD were unaffected by the lesions. These results suggest that the antikindling action of LC stimulation is mediated by the ascending projections of noradrenergic neurons, presumably through enhanced release of noradrenaline. On the other hand, the facilitatory effects of LC stimulation on the development of later stages of seizure and on the duration of AD appear to be independent of the ascending dorsal bundle.
    Experimental Neurology 06/1990; · 4.65 Impact Factor
  • G M Grace, M E Corcoran, R W Skelton
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    ABSTRACT: Once daily for 60 days, hooded rats received unilateral high-frequency stimulation in the hilus of the dentate gyrus (DG), at an intensity sufficient to evoke epileptiform afterdischarge (AD). Although most rats eventually developed generalized stage-5 seizures (Generalized group), some did not progress beyond partial stage-1 or stage-2 seizures (Partial group). Hilar kindling also displayed several other characteristics that distinguished it from typical limbic kindling, including low rate of development, marked instability of the seizures, and little or no growth in duration of AD.
    Brain Research 03/1990; 509(2):249-56. · 2.88 Impact Factor
  • Gloria M. Grace, Michael E. Corcoran, Ronald W. Skelton
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    ABSTRACT: Once daily for 60 days, male hooded rats received unilateral high-frequency stimulation in the hilus of the dentate gyrus (DG), at an intensity sufficient to evoke afterdischarge (AD). Every 2nd day, evoked potentials were recorded from the hilus following stimulation of the PP with single 0.1 ms pulses at 6 current intensities. Changes in synaptic excitability of the dentate granule cells were monitored by measuring the amplitudes of the population spikes; changes in the strength of excitatory synaptic transmission were monitored by measuring the slopes of the excitatory postsynaptic potentials (EPSPs). Control rats, which were not given kindling stimulation, were tested for changes in synaptic transmission and excitability in the same way, at comparable times. In general, hilar stimulation resulted in a large decrease in population spike amplitudes to below baseline and control levels, accompanied by a paradoxical potentiation of EPSPs. Population spike amplitudes decreased more in rats that developed generalized stage-5 seizures (Generalized group) than in rats that did not progress beyond partial seizures despite 60 days of stimulation (Partial group). Conversely, EPSP slopes increased more in the Partial group than in the Generalized group. These results suggest that kindling stimulation may potentiate responsiveness of the directly activated dentate granule cells to inputs from the PP, but at the same time suppress the output of the granule cells resulting from this input. Furthermore, the results indicate that kindling is more closely allied to the suppression of output than to the potentiation of responsiveness to input.
    Brain Research 03/1990; 509(2):257-65. · 2.88 Impact Factor
  • D P Cain, A Raithby, M E Corcoran
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    ABSTRACT: The effect of anesthetic and subanesthetic doses of urethane on the development of amygdala kindled seizures and on the expression of previously kindled seizures was studied in hooded rats. An anesthetic dose of urethane (1.5 g/kg) almost completely eliminated evoked afterdischarge and completely eliminated convulsive behavior in both groups. It also eliminated the seizure response to pentylenetetrazol. Subanesthetic doses of urethane (0.25 and 0.5 g/kg) strongly attenuated the expression of previously kindled seizures. These results suggest that urethane may not be an appropriate anesthetic for the study of epileptiform phenomena.
    Life Sciences 02/1989; 44(17):1201-6. · 2.56 Impact Factor
  • Kirk L. Weller, Michael E. Corcoran
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    ABSTRACT: Kindling of seizures with stimulation of anterior neocortex was examined in control rats and in Brattleboro rats deficient in arginine-vasopressin (AVP). There were no significant differences between control rats, homozygous Brattleboro rats, and heterozygous Brattleboro rats in the rate and pattern of kindling of generalized seizures. Thus AVP is not critically involved in anterior neocortical kindling.
    Brain Research 12/1988; 463(2):390-3. · 2.88 Impact Factor
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    ABSTRACT: Rats were electrically kindled in deep prepyriform cortex (DPC) and in immediately surrounding areas, pyriform cortex, and the basolateral amygdala in an effort to identify an area of the basal forebrain crucially involved in epileptogenesis and the kindling of seizures. Picomolar quantities of carbachol were also microinjected into DPC. All of these areas kindled at equivalent rates. Injection of picomolar quantities of carbachol failed to evoke epileptiform spiking, but injection of nanomolar quantities of carbachol usually evoked epileptiform spiking. Bilateral radiofrequency lesions of the DPC did not affect the rate of electrical kindling of the basolateral amygdala. We conclude that the DPC kindles readily at a rate that is similar to that of surrounding basal forebrain tissue and that the integrity of the DPC is not necessary for basolateral amygdaloid kindling.
    Experimental Neurology 05/1988; 100(1):203-9. · 4.65 Impact Factor
  • J Lewis, V Westerberg, M E Corcoran
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    ABSTRACT: High-performance liquid chromatography with electrochemical detection was used to measure the regional concentrations of monoamines and metabolites in the brains of rats killed 2 or 4 weeks after kindling of generalized seizures with amygdaloid stimulation. Each kindled rat was compared to a yoked control that received brief trains of non-convulsive low-frequency stimulation of the amygdala. Two weeks after kindling we found a significant depletion of noradrenaline (NA) in the ipsilateral frontal cortex, a significant depletion of serotonin (5-HT) in the stimulated amygdala and contralateral hypothalamus, and no significant changes in concentration of dopamine (DA). Four weeks after kindling we found significant depletions of NA in the stimulated amygdala and ipsilateral hypothalamus, a significant depletion of 5-HT in the ipsilateral hippocampus, and no significant changes in DA. These findings generally fail to replicate previous reports of monoaminergic correlates of kindling. Furthermore, the alterations in monoamines produced by kindling do not fall into a simple and readily interpretable pattern.
    Brain Research 03/1987; 403(2):205-12. · 2.88 Impact Factor
  • V Westerberg, M E Corcoran
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    ABSTRACT: The effects of antagonism of muscarinic cholinergic receptors on the development of seizures produced by electrical stimulation of the amygdala (kindling) were assessed in three experiments. Rats pretreated with the muscarinic antagonist scopolamine developed seizures more slowly than did untreated rats. Whereas scopolamine retarded the development of seizures in a dose-dependent manner, it did not affect the intensity or duration of seizures when administered to kindled control rats. Pretreatment with methylscopolamine, a quaternary derivative of scopolamine that does not readily cross the blood-brain barrier, did not affect the rate of development of seizures, nor did it affect established seizures. Thus the prophylactic effects of scopolamine are produced in the central nervous system and not in the periphery. The results from these experiments are consistent with the idea that central cholinergic or cholinoceptive neurons are critically involved in amygdala kindling.
    Experimental Neurology 02/1987; 95(1):194-206. · 4.65 Impact Factor
  • D P Cain, J Plant, S Rouleau, M E Corcoran
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    ABSTRACT: In an attempt to kindle seizures with arginine-vasopressin (AVP), we injected AVP into the amygdala or hippocampus of rats. Although behavioral and electrographic alterations were sometimes observed, seizures failed to develop, even in rats that had previously been kindled with electrical stimulation. This and previous failures to kindle seizures by intraventricular injections of AVP call into question the possibility of AVP kindling.
    Life Sciences 04/1986; 38(11):985-9. · 2.56 Impact Factor
  • D P Cain, M E Corcoran
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    ABSTRACT: Repeated spaced injection of small amounts of beta-endorphin or Met-enkephalin into the hippocampus or posterior amygdala of the rat led to the development of kindled generalized convulsions. Similar injection of morphine into the hippocampus or anterior amygdala resulted in epileptiform spiking followed by tolerance. The epileptiform spiking and convulsive behavior varied in a dose-related manner. Naloxone blocked or greatly attenuated the electrographic seizure and convulsive behavior. Prior kindling with beta-endorphin or Met-enkephalin significantly facilitated electrical kindling of the amygdala. Handling or conspecific threat potentiated the epileptiform spiking and convulsive behavior in some cases. The results indicate that the epileptogenic response to intracerebrally applied opioid peptides is site-specific within the rat brain, and they support the idea that endogenous opioid mechanisms may play a role in convulsive seizures. They also suggest a possible opiate-based mechanism for the stress-induced exacerbation of seizures.
    Brain Research 08/1985; 338(2):327-36. · 2.88 Impact Factor

Publication Stats

2k Citations
256.49 Total Impact Points

Institutions

  • 1979–1997
    • University of Victoria
      • Department of Psychology
      Victoria, British Columbia, Canada
  • 1980–1990
    • The University of Western Ontario
      • Department of Psychology
      London, Ontario, Canada
  • 1973–1980
    • University of British Columbia - Vancouver
      • • Department of Psychiatry
      • • Faculty of Medicine
      Vancouver, British Columbia, Canada
  • 1971–1974
    • McGill University
      • Department of Psychology
      Montréal, Quebec, Canada