Publications

2004
Tormos JM, Pascual-Leone A, Wagner T, Merabet L, Kobayashi M, Theoret H. Modulation of right motor cortex excitability without awareness following presentation of masked self-images. Brain research. Cognitive brain research. 2004;20 :54-7. Publisher's VersionAbstract

The neural substrates of self-awareness have been studied with a variety of neurophysiological and behavioral tools. In the present study, unconscious modulation of corticospinal excitability following presentation of self-images was probed with transcranial magnetic stimulation (TMS). TMS-induced motor evoked potentials (MEP) were collected from the contralateral first dorsal interosseus (FDI) muscle while subjects viewed masked pictures of their own face. MEP amplitudes were compared to those obtained when pictures of strangers were masked. Masked self-images induced a relative increase in corticospinal excitability when TMS was applied to the right primary motor cortex. These results demonstrate the utility of TMS to probe unconscious processing and support the notion of hemispheric asymmetry in the processing of self-images.

Pascual-Leone A, Merabet L, Kobayashi M, Halligan E, Theoret H. Unconscious modulation of motor cortex excitability revealed with transcranial magnetic stimulation. Experimental brain research. Experimentelle Hirnforschung. Experimentation cerebrale. 2004;155 :261-4. Publisher's VersionAbstract

The neuronal effects of sensory events that do not enter conscious awareness have been reported in numerous pathological conditions and in normal subjects. In the present study, unconscious modulation of corticospinal excitability was probed in healthy volunteers with transcranial magnetic stimulation (TMS). TMS-induced motor evoked potentials (MEPs) were collected from the first dorsal interosseus muscle while subjects performed a masked semantic priming task that has been shown to elicit covert motor cortex activations. Our data show that the amplitude of the MEPs is modulated by an unseen prime, in line with temporal patterns revealed with event related potentials. These data confirm previous reports showing specific motor neural responses associated with an unseen visual stimulus and establish TMS as a valuable tool in the study of the neural correlates of consciousness.

Stickgold R, Pascual-Leone A, Alterescu K, Warde A, Maguire D, Merabet LB. Visual hallucinations during prolonged blindfolding in sighted subjects. Journal of neuro-ophthalmology : the official journal of the North American Neuro-Ophthalmology Society. 2004;24 :109-13. Publisher's VersionAbstract

The authors report the occurrence of visual hallucinations of varying complexity in 13 normal subjects after sudden, complete, and prolonged visual deprivation. The subjects were all healthy individuals with no history of cognitive dysfunction, psychosis, or ocular pathology. They wore a specially designed blindfold for a period of five consecutive days (96 hours) and were asked to record their daily experiences using a hand-held microcassette recorder. Ten (77%) of the subjects reported visual hallucinations, which were both simple (bright spots of light) and complex (faces, landscapes, ornate objects). The onset of hallucinations was generally after the first day of blindfolding. Subjects were insightful as to their unreal nature. These results indicate that rapid and complete visual deprivation is sufficient to induce visual hallucinations in normal subjects.

Hsiao S, Pascual-Leone A, Andrews J, Murray B, Thut G, Merabet L. Feeling by sight or seeing by touch?. Neuron. 2004;42 :173-9. Publisher's VersionAbstract

We have addressed the role of occipital and somatosensory cortex in a tactile discrimination task. Sight-ed and congenitally blind subjects rated the roughness and distance spacing for a series of raised dot patterns. When judging roughness, intermediate dot spacings were perceived as being the most rough, while distance judgments generated a linear relation. Low-frequency rTMS applied to somatosensory cortex disrupted roughness without affecting distance judgments, while rTMS to occipital cortex disrupted distance but not roughness judgments. We also tested an early blind patient with bilateral occipital cortex damage. Her performance on the roughness determination task was normal; however, she was greatly impaired with distance judgments. The findings suggest a double-dissociation effect in which roughness and distance are primarily processed in somatosensory and occipital cortex, respectively. The differential effect of rTMS on task performance and corroborative clinical evidence suggest that occipital cortex is engaged in tactile tasks requiring fine spatial discrimination.

Marcolin MA, Pascual-Leone A, Merabet L, Fregni F. Modulation in motor threshold after a severe episode of gastrointestinal distress. The journal of ECT. 2004;20 :50-1. Publisher's VersionAbstract
n/a
2003
Merabet LB, Kobayashi M, Barton J, Pascual-Leone A. Suppression of complex visual hallucinatory experiences by occipital transcranial magnetic stimulation: a case report. Neurocase. 2003;9 (5) :436-40.Abstract
Abstract We report a patient with visual hallucinations and illusions along with an associated visual field defect after bilateral ischemic damage to his occipital visual cortex. These hallucinations were long-standing and of both simple and complex (well-formed) type. Application of low frequency (1 Hz) repetitive Transcranial Magnetic Stimulation (rTMS) to the occipital cortex led to a complete cessation of visual hallucinatory symptoms. The use of TMS to probe the neurophysiology, and possibly alleviate, visual hallucinatory experiences is discussed.
Merabet LB, Theoret H, Pascual-Leone A. Transcranial magnetic stimulation as an investigative tool in the study of visual function. Optom Vis Sci. 2003;80 (5) :356-68.Abstract
Transcranial magnetic stimulation (TMS) is a novel and powerful probe to study the relationship between human brain function and behavior. TMS is being widely used to investigate memory, language, attention, learning, and motor function and is even being utilized therapeutically in the treatment of depression. Some of the earliest applications of TMS have been directed toward the investigation of human visual perception. For example, a strong TMS pulse delivered to the occipital cortex in a sighted or even blind individual can evoke the sensation of perceiving light (visual phosphenes). TMS can also be used to suppress visual perception and investigate the timing of visual information processing. Furthermore, the functional connectivity between different brain areas can be mapped using TMS, thus establishing a causal link between visual cortical function and visual perception. The present article is meant as an overview of the technique of TMS and a review of the literature as it pertains to the study of visual function. The application of TMS in the diagnosis as well as possible therapeutic use in various visual disorders is also discussed.
Pascual-Leone A, Theoret H, Merabet LB. Transcranial magnetic stimulation as an investigative tool in the study of visual function. Optometry and vision science : official publication of the American Academy of Optometry. 2003;80 :356-68. Publisher's VersionAbstract

Transcranial magnetic stimulation (TMS) is a novel and powerful probe to study the relationship between human brain function and behavior. TMS is being widely used to investigate memory, language, attention, learning, and motor function and is even being utilized therapeutically in the treatment of depression. Some of the earliest applications of TMS have been directed toward the investigation of human visual perception. For example, a strong TMS pulse delivered to the occipital cortex in a sighted or even blind individual can evoke the sensation of perceiving light (visual phosphenes). TMS can also be used to suppress visual perception and investigate the timing of visual information processing. Furthermore, the functional connectivity between different brain areas can be mapped using TMS, thus establishing a causal link between visual cortical function and visual perception. The present article is meant as an overview of the technique of TMS and a review of the literature as it pertains to the study of visual function. The application of TMS in the diagnosis as well as possible therapeutic use in various visual disorders is also discussed.

Pascual-Leone A, Barton J, Kobayashi M, Merabet LB. Suppression of complex visual hallucinatory experiences by occipital transcranial magnetic stimulation: a case report. Neurocase. 2003;9 :436-40. Publisher's VersionAbstract

Abstract We report a patient with visual hallucinations and illusions along with an associated visual field defect after bilateral ischemic damage to his occipital visual cortex. These hallucinations were long-standing and of both simple and complex (well-formed) type. Application of low frequency (1 Hz) repetitive Transcranial Magnetic Stimulation (rTMS) to the occipital cortex led to a complete cessation of visual hallucinatory symptoms. The use of TMS to probe the neurophysiology, and possibly alleviate, visual hallucinatory experiences is discussed.

2001
Casanova C, Merabet L, Desautels A, Minville K. Higher-order motion processing in the pulvinar. Prog Brain Res. 2001;134 :71-82.Abstract
Thalamic nuclei have long been considered as passive relay stations for sensory signals en route to the cerebral cortex, where higher level processing occurs. In recent years, it has been proposed that thalamic nuclei may actively participate in the processing of specific information in conjunction with cortical areas. In support of this hypothesis, we recently discovered that neurons in the main extrageniculate visual nucleus, the pulvinar, exhibit higher-order visual properties that were, until now, only associated with higher-order cortical areas. Pulvinar neurons can indeed code the veridical direction of a moving plaid pattern, indicating that these cells can integrate ambiguous signals into a coherent percept. This finding as well as our demonstration that there are cortico-thalamo-cortical loops involved in complex motion analysis open promising avenues in unraveling the function of the pulvinar complex in normal vision.
Minville K, Desautels A, Merabet L, Casanova C. Higher-order motion processing in the pulvinar. Progress in brain research. 2001;134 :71-82. Publisher's VersionAbstract

Thalamic nuclei have long been considered as passive relay stations for sensory signals en route to the cerebral cortex, where higher level processing occurs. In recent years, it has been proposed that thalamic nuclei may actively participate in the processing of specific information in conjunction with cortical areas. In support of this hypothesis, we recently discovered that neurons in the main extrageniculate visual nucleus, the pulvinar, exhibit higher-order visual properties that were, until now, only associated with higher-order cortical areas. Pulvinar neurons can indeed code the veridical direction of a moving plaid pattern, indicating that these cells can integrate ambiguous signals into a coherent percept. This finding as well as our demonstration that there are cortico-thalamo-cortical loops involved in complex motion analysis open promising avenues in unraveling the function of the pulvinar complex in normal vision.

2000
Merabet L, Minville K, Ptito M, Casanova C. Responses of neurons in the cat posteromedial lateral suprasylvian cortex to moving texture patterns. Neuroscience. 2000;97 (4) :611-23.Abstract
The posteromedial lateral suprasylvian cortex represents a point of convergence between the geniculostriate and extrageniculostriate visual pathways. Given its purported role in motion analysis and the conflicting reports regarding the texture sensitivity of this area, we have investigated the response properties of cells in PMLS to moving texture patterns ("visual noise"). In contrast to previous reports, we have found that a large majority of cells (80.1%) responds to the motion of a texture pattern with sustained discharges. In general, responses to noise were more broadly tuned for direction compared to gratings; however, direction selectivity appeared more pronounced in response to noise. The majority of cells was selective for drift velocity of the noise pattern (mean optimal velocity: 26.7 degrees /s). Velocity tuning was comparable to that of its principal thalamic input, the lateral posterior pulvinar nucleus. In general, responsiveness of cells in the posteromedial lateral suprasylvian cortex increased with increasing texture element size, although some units were tuned to smaller element sizes than the largest presented. Finally, the magnitude of these noise responses was dependent on the area of the visual field stimulated. In general, a stimulus corresponding to roughly twice the size of the receptive field was required to elicit an equivalent half-maximal response to that for gratings. The results of this study indicate that the majority of cells in the posteromedial lateral suprasylvian cortex can be driven by the motion of a fine texture field, and highlight the importance of this area in motion analysis.
Casanova C, Ptito M, Minville K, Merabet L. Responses of neurons in the cat posteromedial lateral suprasylvian cortex to moving texture patterns. Neuroscience. 2000;97 :611-23. Publisher's VersionAbstract

The posteromedial lateral suprasylvian cortex represents a point of convergence between the geniculostriate and extrageniculostriate visual pathways. Given its purported role in motion analysis and the conflicting reports regarding the texture sensitivity of this area, we have investigated the response properties of cells in PMLS to moving texture patterns ("visual noise"). In contrast to previous reports, we have found that a large majority of cells (80.1%) responds to the motion of a texture pattern with sustained discharges. In general, responses to noise were more broadly tuned for direction compared to gratings; however, direction selectivity appeared more pronounced in response to noise. The majority of cells was selective for drift velocity of the noise pattern (mean optimal velocity: 26.7 degrees /s). Velocity tuning was comparable to that of its principal thalamic input, the lateral posterior pulvinar nucleus. In general, responsiveness of cells in the posteromedial lateral suprasylvian cortex increased with increasing texture element size, although some units were tuned to smaller element sizes than the largest presented. Finally, the magnitude of these noise responses was dependent on the area of the visual field stimulated. In general, a stimulus corresponding to roughly twice the size of the receptive field was required to elicit an equivalent half-maximal response to that for gratings. The results of this study indicate that the majority of cells in the posteromedial lateral suprasylvian cortex can be driven by the motion of a fine texture field, and highlight the importance of this area in motion analysis.

1998
Merabet L, Desautels A, Minville K, Casanova C. Motion integration in a thalamic visual nucleus. Nature. 1998;396 (6708) :265-8.Abstract
Thalamic nuclei have long been regarded as passive relay stations for sensory information en route to higher level processing in the cerebral cortex. Recently, physiological and theoretical studies have reassessed the role of the thalamus and it has been proposed that thalamic nuclei may actively participate with cortical areas in processing specific information. In support of this idea, we now show that a subset of neurons in an extrageniculate visual nucleus, the lateral-posterior pulvinar complex, can signal the true direction of motion of a plaid pattern, indicating that thalamic cells can integrate different motion signals into a coherent moving percept. This is the first time that these computations have been found to occur outside the higher-order cortical areas. Our findings implicate extrageniculate cortico-thalamo-cortical loops in the dynamic processing of image motion, and, more generally, as basic computational modules involved in analysing specific features of complex visual scenes.
Casanova C, Minville K, Desautels A, Merabet L. Motion integration in a thalamic visual nucleus. Nature. 1998;396 :265-8. Publisher's VersionAbstract

Thalamic nuclei have long been regarded as passive relay stations for sensory information en route to higher level processing in the cerebral cortex. Recently, physiological and theoretical studies have reassessed the role of the thalamus and it has been proposed that thalamic nuclei may actively participate with cortical areas in processing specific information. In support of this idea, we now show that a subset of neurons in an extrageniculate visual nucleus, the lateral-posterior pulvinar complex, can signal the true direction of motion of a plaid pattern, indicating that thalamic cells can integrate different motion signals into a coherent moving percept. This is the first time that these computations have been found to occur outside the higher-order cortical areas. Our findings implicate extrageniculate cortico-thalamo-cortical loops in the dynamic processing of image motion, and, more generally, as basic computational modules involved in analysing specific features of complex visual scenes.

1997
Merabet L, de Gasparo M, Casanova C. Dose-dependent inhibitory effects of angiotensin II on visual responses of the rat superior colliculus: AT1 and AT2 receptor contributions. Neuropeptides. 1997;31 (5) :469-81.Abstract
Angiotensin II (Ang II) has traditionally been regarded as a peripherally circulating and acting hormone involved in fluid homeostasis and blood pressure regulation. With the rather recent localization of Ang II receptors within the mammalian brain, renewed interest has emerged in the hope of elucidating the central impact and function of this hormone. One region that has been clearly demonstrated to express Ang II receptors is the superior colliculus (SC). This mesencephalic structure plays an important role in sensory visuomotor integration. Receptors for Ang II (of both the AT1 and AT2 subtypes) have been localized within the superficial layers of this structure, i.e. the areas that are visually responsive. In the hopes of characterizing the role of Ang II in the SC, we have attempted to physiologically activate these receptors in vivo and observe the effects of Ang II on visually evoked responses. In the attempt to identify the receptor subtype(s) responsible in mediating these effects, Ang II was injected concomitantly with selective receptor ligands. Experiments were performed on adult rats prepared in classical fashion for electrophysiological studies. Through microinjection of Ang II, and the simultaneous recording of visually evoked potentials to flash stimulation, we have observed that this peptide yields a strong suppressive effect on visual neuronal activity. By injecting Ang II at various concentrations (10(-3)-10(-10) M), we have further observed that the effects of this peptide express a dose-related dependency. Injection of Ang II in progressively more ventral layers yielded less pronounced effects, demonstrating physiologically the discrete localization of these receptors in the stratum griseum superficiale. Coinjection of Ang II with Losartan yielded a near complete blockade of Ang II suppressive effects, suggesting that AT1 receptors play a prominent role in mediating these responses. However, coinjection of Ang II with PD 123,319 yielded a slight, yet significant partial blockade. Coinjection of Ang II with both the AT1 and AT2 receptor antagonists yielded a complete blockade of the Ang II effect. Finally, some of the results suggest that the AT2 receptor ligand CGP 42,112 may possess agonist properties. Taken together, these findings suggest that the AT1 receptor is predominantly involved in mediating Ang II responses in the SC and there also appears to be some indication of AT2 receptor involvement. However, the underlying mechanisms (such as receptor interactions), the exact specificity of the ligands used, and the possibility of other receptor subtype implication have yet to be explored fully.
Casanova C, de Gasparo M, Merabet L. Dose-dependent inhibitory effects of angiotensin II on visual responses of the rat superior colliculus: AT1 and AT2 receptor contributions. Neuropeptides. 1997;31 :469-81. Publisher's VersionAbstract

Angiotensin II (Ang II) has traditionally been regarded as a peripherally circulating and acting hormone involved in fluid homeostasis and blood pressure regulation. With the rather recent localization of Ang II receptors within the mammalian brain, renewed interest has emerged in the hope of elucidating the central impact and function of this hormone. One region that has been clearly demonstrated to express Ang II receptors is the superior colliculus (SC). This mesencephalic structure plays an important role in sensory visuomotor integration. Receptors for Ang II (of both the AT1 and AT2 subtypes) have been localized within the superficial layers of this structure, i.e. the areas that are visually responsive. In the hopes of characterizing the role of Ang II in the SC, we have attempted to physiologically activate these receptors in vivo and observe the effects of Ang II on visually evoked responses. In the attempt to identify the receptor subtype(s) responsible in mediating these effects, Ang II was injected concomitantly with selective receptor ligands. Experiments were performed on adult rats prepared in classical fashion for electrophysiological studies. Through microinjection of Ang II, and the simultaneous recording of visually evoked potentials to flash stimulation, we have observed that this peptide yields a strong suppressive effect on visual neuronal activity. By injecting Ang II at various concentrations (10(-3)-10(-10) M), we have further observed that the effects of this peptide express a dose-related dependency. Injection of Ang II in progressively more ventral layers yielded less pronounced effects, demonstrating physiologically the discrete localization of these receptors in the stratum griseum superficiale. Coinjection of Ang II with Losartan yielded a near complete blockade of Ang II suppressive effects, suggesting that AT1 receptors play a prominent role in mediating these responses. However, coinjection of Ang II with PD 123,319 yielded a slight, yet significant partial blockade. Coinjection of Ang II with both the AT1 and AT2 receptor antagonists yielded a complete blockade of the Ang II effect. Finally, some of the results suggest that the AT2 receptor ligand CGP 42,112 may possess agonist properties. Taken together, these findings suggest that the AT1 receptor is predominantly involved in mediating Ang II responses in the SC and there also appears to be some indication of AT2 receptor involvement. However, the underlying mechanisms (such as receptor interactions), the exact specificity of the ligands used, and the possibility of other receptor subtype implication have yet to be explored fully.

1994
Merabet L, de Gasparo M, Casanova C. Neuromodulatory effects of angiotensin II in the visual layers of the rat superior colliculus. Neuroreport. 1994;5 (18) :2649-52.Abstract
Recent autoradiographic studies have revealed the presence of both AT1 and AT2 angiotensin II (AngII) receptor subtypes in the superficial layers of the rat superior colliculus (SC). We have investigated the effects of activating these receptors on visually evoked potentials (VEP) in the SC of adult rats. A recording injecting microelectrode filled with AngII was lowered into the superficial layers of the SC. AngII was injected at concentrations varying from 10(-4) to 10(-10) M. Injection of the peptide yielded a reduction in the amplitude of the VEP. This reduction usually occurred within 2-3 min following AngII injection with a 50% recovery of most of the signal 20-30 min thereafter. AngII did not modify the signal when injected in collicular layers ventral to the stratum opticum. Furthermore, concomitant injection of AngII with the specific AT, receptor antagonist Losartan failed to reduce the evoked response suggesting that the effects of AngII in the SC are likely mediated by AT1 receptors.
Casanova C, de Gasparo M, Merabet L. Neuromodulatory effects of angiotensin II in the visual layers of the rat superior colliculus. Neuroreport. 1994;5 :2649-52. Publisher's VersionAbstract

Recent autoradiographic studies have revealed the presence of both AT1 and AT2 angiotensin II (AngII) receptor subtypes in the superficial layers of the rat superior colliculus (SC). We have investigated the effects of activating these receptors on visually evoked potentials (VEP) in the SC of adult rats. A recording injecting microelectrode filled with AngII was lowered into the superficial layers of the SC. AngII was injected at concentrations varying from 10(-4) to 10(-10) M. Injection of the peptide yielded a reduction in the amplitude of the VEP. This reduction usually occurred within 2-3 min following AngII injection with a 50% recovery of most of the signal 20-30 min thereafter. AngII did not modify the signal when injected in collicular layers ventral to the stratum opticum. Furthermore, concomitant injection of AngII with the specific AT, receptor antagonist Losartan failed to reduce the evoked response suggesting that the effects of AngII in the SC are likely mediated by AT1 receptors.

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