Publications

2010
Bolognini N, Senna I, Maravita A, Pascual-Leone A, Merabet LB. Auditory enhancement of visual phosphene perception: the effect of temporal and spatial factors and of stimulus intensity. Neurosci Lett. 2010;477 (3) :109-14.Abstract
Multisensory integration of information from different sensory modalities is an essential component of perception. Neurophysiological studies have revealed that audiovisual interactions occur early in time and even within sensory cortical areas believed to be modality-specific. Here we investigated the effect of auditory stimuli on visual perception of phosphenes induced by transcranial magnetic stimulation (TMS) delivered to the occipital visual cortex. TMS applied at subthreshold intensity led to the perception of phosphenes when coupled with an auditory stimulus presented within close spatiotemporal congruency at the expected retinotopic location of the phosphene percept. The effect was maximal when the auditory stimulus preceded the occipital TMS pulse by 40 ms. Follow-up experiments confirmed a high degree of temporal and spatial specificity of this facilitatory effect. Furthermore, audiovisual facilitation was only present at subthreshold TMS intensity for the phosphenes, suggesting that suboptimal levels of excitability within unisensory cortices may be better suited for enhanced crossmodal interactions. Overall, our findings reveal early auditory-visual interactions due to the enhancement of visual cortical excitability by auditory stimuli. These interactions may reflect an underlying anatomical connectivity between unisensory cortices.
Merabet LB, Pascual-Leone A. Neural reorganization following sensory loss: the opportunity of change. Nat Rev Neurosci. 2010;11 (1) :44-52.Abstract
There is growing evidence that sensory deprivation is associated with crossmodal neuroplastic changes in the brain. After visual or auditory deprivation, brain areas that are normally associated with the lost sense are recruited by spared sensory modalities. These changes underlie adaptive and compensatory behaviours in blind and deaf individuals. Although there are differences between these populations owing to the nature of the deprived sensory modality, there seem to be common principles regarding how the brain copes with sensory loss and the factors that influence neuroplastic changes. Here, we discuss crossmodal neuroplasticity with regards to behavioural adaptation after sensory deprivation and highlight the possibility of maladaptive consequences within the context of rehabilitation.
Obretenova S, Halko MA, Plow EB, Pascual-Leone A, Merabet LB. Neuroplasticity associated with tactile language communication in a deaf-blind subject. Front Hum Neurosci. 2010;3 :60.Abstract
A long-standing debate in cognitive neuroscience pertains to the innate nature of language development and the underlying factors that determine this faculty. We explored the neural correlates associated with language processing in a unique individual who is early blind, congenitally deaf, and possesses a high level of language function. Using functional magnetic resonance imaging (fMRI), we compared the neural networks associated with the tactile reading of words presented in Braille, Print on Palm (POP), and a haptic form of American Sign Language (haptic ASL or hASL). With all three modes of tactile communication, indentifying words was associated with robust activation within occipital cortical regions as well as posterior superior temporal and inferior frontal language areas (lateralized within the left hemisphere). In a normally sighted and hearing interpreter, identifying words through hASL was associated with left-lateralized activation of inferior frontal language areas however robust occipital cortex activation was not observed. Diffusion tensor imaging -based tractography revealed differences consistent with enhanced occipital-temporal connectivity in the deaf-blind subject. Our results demonstrate that in the case of early onset of both visual and auditory deprivation, tactile-based communication is associated with an extensive cortical network implicating occipital as well as posterior superior temporal and frontal associated language areas. The cortical areas activated in this deaf-blind subject are consistent with characteristic cortical regions previously implicated with language. Finally, the resilience of language function within the context of early and combined visual and auditory deprivation may be related to enhanced connectivity between relevant cortical areas.
Merabet LB, Pascual-Leone A, Plow EB, Halko MA, Obretenova S. Neuroplasticity associated with tactile language communication in a deaf-blind subject. Frontiers in human neuroscience. 2010;3 :60. Publisher's VersionAbstract

A long-standing debate in cognitive neuroscience pertains to the innate nature of language development and the underlying factors that determine this faculty. We explored the neural correlates associated with language processing in a unique individual who is early blind, congenitally deaf, and possesses a high level of language function. Using functional magnetic resonance imaging (fMRI), we compared the neural networks associated with the tactile reading of words presented in Braille, Print on Palm (POP), and a haptic form of American Sign Language (haptic ASL or hASL). With all three modes of tactile communication, indentifying words was associated with robust activation within occipital cortical regions as well as posterior superior temporal and inferior frontal language areas (lateralized within the left hemisphere). In a normally sighted and hearing interpreter, identifying words through hASL was associated with left-lateralized activation of inferior frontal language areas however robust occipital cortex activation was not observed. Diffusion tensor imaging -based tractography revealed differences consistent with enhanced occipital-temporal connectivity in the deaf-blind subject. Our results demonstrate that in the case of early onset of both visual and auditory deprivation, tactile-based communication is associated with an extensive cortical network implicating occipital as well as posterior superior temporal and frontal associated language areas. The cortical areas activated in this deaf-blind subject are consistent with characteristic cortical regions previously implicated with language. Finally, the resilience of language function within the context of early and combined visual and auditory deprivation may be related to enhanced connectivity between relevant cortical areas.

Pascual-Leone A, Merabet LB. Neural reorganization following sensory loss: the opportunity of change. Nature reviews. Neuroscience. 2010;11 :44-52. Publisher's VersionAbstract

There is growing evidence that sensory deprivation is associated with crossmodal neuroplastic changes in the brain. After visual or auditory deprivation, brain areas that are normally associated with the lost sense are recruited by spared sensory modalities. These changes underlie adaptive and compensatory behaviours in blind and deaf individuals. Although there are differences between these populations owing to the nature of the deprived sensory modality, there seem to be common principles regarding how the brain copes with sensory loss and the factors that influence neuroplastic changes. Here, we discuss crossmodal neuroplasticity with regards to behavioural adaptation after sensory deprivation and highlight the possibility of maladaptive consequences within the context of rehabilitation.

Merabet LB, Pascual-Leone A, Maravita A, Senna I, Bolognini N. Auditory enhancement of visual phosphene perception: the effect of temporal and spatial factors and of stimulus intensity. Neuroscience letters. 2010;477 :109-14. Publisher's VersionAbstract

Multisensory integration of information from different sensory modalities is an essential component of perception. Neurophysiological studies have revealed that audiovisual interactions occur early in time and even within sensory cortical areas believed to be modality-specific. Here we investigated the effect of auditory stimuli on visual perception of phosphenes induced by transcranial magnetic stimulation (TMS) delivered to the occipital visual cortex. TMS applied at subthreshold intensity led to the perception of phosphenes when coupled with an auditory stimulus presented within close spatiotemporal congruency at the expected retinotopic location of the phosphene percept. The effect was maximal when the auditory stimulus preceded the occipital TMS pulse by 40 ms. Follow-up experiments confirmed a high degree of temporal and spatial specificity of this facilitatory effect. Furthermore, audiovisual facilitation was only present at subthreshold TMS intensity for the phosphenes, suggesting that suboptimal levels of excitability within unisensory cortices may be better suited for enhanced crossmodal interactions. Overall, our findings reveal early auditory-visual interactions due to the enhancement of visual cortical excitability by auditory stimuli. These interactions may reflect an underlying anatomical connectivity between unisensory cortices.

2009
Plow EB, Maguire S, Obretenova S, Pascual-Leone A, Merabet LB. Approaches to rehabilitation for visual field defects following brain lesions. Expert Rev Med Devices. 2009;6 (3) :291-305.Abstract
Visual field defects often result from stroke and brain injury. The resulting visual impairment can be debilitating for patients, impeding daily activities such as reading and mobility. Historically, it was believed that there was little opportunity for restoration of function following visual system damage. However, the development of various visual rehabilitative strategies suggests that visual field defects are partially repairable and a certain degree of function can be improved. While this provides hope for patients, many of these strategies have been met with skepticism within the clinical and scientific communities. Further development of these strategies through carefully designed studies could validate their efficacy and reveal underlying mechanisms. Novel techniques, aimed at enhancing the effect of these rehabilitative strategies, are also discussed.
Merabet LB, Battelli L, Obretenova S, Maguire S, Meijer P, Pascual-Leone A. Functional recruitment of visual cortex for sound encoded object identification in the blind. Neuroreport. 2009;20 (2) :132-8.Abstract
Individuals using a visual-to-auditory sensory substitution device (SSD) called 'The vOICe' can identify objects in their environment through images encoded by sound. We have shown that identifying objects with this SSD is associated with activation of occipital visual areas. Here, we show that repetitive transcranial magnetic stimulation (rTMS) delivered to a specific area of occipital cortex (identified by functional MRI) profoundly impairs a blind user's ability to identify objects. rTMS delivered to the same site had no effect on a visual imagery task. The task and site-specific disruptive effect of rTMS in this individual suggests that the cross-modal recruitment of occipital visual areas is functional in nature and critical to the patient's ability to process and decode the image sounds using this SSD.
Merabet LB, Jaime Sanchez. Audio-Based Navigation Using Virtual Environments: Combining Technology and Neuroscience. AER Journal: Research and Practice in Visual Impairment and Blindness. 2009;2 (3) :128-137. WebsiteAbstract

For individuals who are blind, navigation requires the construction of a cognitive spatial map of one’s
surrounding environment. Novel technological approaches are being developed to teach and enhance
this cognitive skill. Here, we discuss user-centered, audio-based methods of virtual navigation
implemented through computer gaming. The immersive, engaging, and heavily interactive nature of the
software allows for the generation of mental spatial representations that can be transferred to real-world
navigation tasks and, furthermore, promotes creativity and problem-solving skills. Navigation with virtual
environments also represents a tractable testing platform to collect quantifiable metrics and monitor
learning. Combining this technology with neuroscience research can be used to investigate brain
mechanisms related to sensory processing in the absence of vision.

Merabet LB, Pascual-Leone A, Obretenova S, Maguire S, Plow EB. Approaches to rehabilitation for visual field defects following brain lesions. Expert review of medical devices. 2009;6 :291-305. Publisher's VersionAbstract

Visual field defects often result from stroke and brain injury. The resulting visual impairment can be debilitating for patients, impeding daily activities such as reading and mobility. Historically, it was believed that there was little opportunity for restoration of function following visual system damage. However, the development of various visual rehabilitative strategies suggests that visual field defects are partially repairable and a certain degree of function can be improved. While this provides hope for patients, many of these strategies have been met with skepticism within the clinical and scientific communities. Further development of these strategies through carefully designed studies could validate their efficacy and reveal underlying mechanisms. Novel techniques, aimed at enhancing the effect of these rehabilitative strategies, are also discussed.

Meijer P, Pascual-Leone A, Maguire S, Obretenova S, Battelli L, Merabet LB. Functional recruitment of visual cortex for sound encoded object identification in the blind. Neuroreport. 2009;20 :132-8. Publisher's VersionAbstract

Individuals using a visual-to-auditory sensory substitution device (SSD) called 'The vOICe' can identify objects in their environment through images encoded by sound. We have shown that identifying objects with this SSD is associated with activation of occipital visual areas. Here, we show that repetitive transcranial magnetic stimulation (rTMS) delivered to a specific area of occipital cortex (identified by functional MRI) profoundly impairs a blind user's ability to identify objects. rTMS delivered to the same site had no effect on a visual imagery task. The task and site-specific disruptive effect of rTMS in this individual suggests that the cross-modal recruitment of occipital visual areas is functional in nature and critical to the patient's ability to process and decode the image sounds using this SSD.

2008
Cattaneo Z, Merabet LB, Bhatt E, Vecchi T. Effects of complete monocular deprivation in visuo-spatial memory. Brain Res Bull. 2008;77 (2-3) :112-6.Abstract
Monocular deprivation has been associated with both specific deficits and enhancements in visual perception and processing. In this study, performance on a visuo-spatial memory task was compared in congenitally monocular individuals and sighted control individuals viewing monocularly (i.e., patched) and binocularly. The task required the individuals to view and memorize a series of target locations on two-dimensional matrices. Overall, congenitally monocular individuals performed worse than sighted individuals (with a specific deficit in simultaneously maintaining distinct spatial representations in memory), indicating that the lack of binocular visual experience affects the way visual information is represented in visuo-spatial memory. No difference was observed between the monocular and binocular viewing control groups, suggesting that early monocular deprivation affects the development of cortical mechanisms mediating visuo-spatial cognition.
Cattaneo Z, Bhatt E, Merabet LB, Pece A, Vecchi T. The influence of reduced visual acuity on age-related decline in spatial working memory: an investigation. Neuropsychol Dev Cogn B Aging Neuropsychol Cogn. 2008;15 (6) :687-702.Abstract
To investigate the relationship between visual acuity and cognitive function with aging, we compared low-vision and normally-sighted young and elderly individuals on a spatial working memory (WM) task. The task required subjects to memorise target locations on different matrices after perceiving them visually or haptically. The haptic modality was included as a control to look at the effect of aging on memory without the confounding effect of visual deficit. Overall, age and visual status did not interact to affect WM accuracy, suggesting that age does not exaggerate the effects of visual deprivation. Young participants performed better than the elderly only when the task required more operational processes (i.e., integration of information). Sighted participants outperformed the visually impaired regardless of testing modality suggesting that the effect of the visual deficit is not confined to only the most peripheral levels of information processing. These findings suggest that vision, being the primary sensory modality, tends to shape the general supramodal mechanisms of memory.
Bermpohl F, Pascual-Leone A, Amedi A, Merabet LB, Fregni F, Wrase J, Schlagenhauf F, Bauer M, Heinz A, Schlaug G, et al. Novelty seeking modulates medial prefrontal activity during the anticipation of emotional stimuli. Psychiatry Res. 2008;164 (1) :81-5.Abstract
In a functional magnetic resonance imaging experiment, expectancy cues signaling emotional stimuli were used to study the personality trait of novelty seeking. BOLD responses to emotional expectancy were positively correlated with novelty-seeking scores in the medial prefrontal cortex. This correlation was strongest for the sub-dimension of exploratory excitability.
Boggio PS, Sultani N, Fecteau S, Merabet L, Mecca T, Pascual-Leone A, Basaglia A, Fregni F. Prefrontal cortex modulation using transcranial DC stimulation reduces alcohol craving: a double-blind, sham-controlled study. Drug Alcohol Depend. 2008;92 (1-3) :55-60.Abstract
BACKGROUND: Functional neuroimaging studies have shown that specific brain areas are associated with alcohol craving including the dorsolateral prefrontal cortex (DLPFC). We tested whether modulation of DLPFC using transcranial direct current stimulation (tDCS) could alter alcohol craving in patients with alcohol dependence while being exposed to alcohol cues. METHODS: We performed a randomized sham-controlled study in which 13 subjects received sham and active bilateral tDCS delivered to DLPFC (anodal left/cathodal right and anodal right/cathodal left). For sham stimulation, the electrodes were placed at the same positions as in active stimulation; however, the stimulator was turned off after 30s of stimulation. Subjects were presented videos depicting alcohol consumption to increase alcohol craving. RESULTS: Our results showed that both anodal left/cathodal right and anodal right/cathodal left significantly decreased alcohol craving compared to sham stimulation (p<0.0001). In addition, we found that following treatment, craving could not be further increased by alcohol cues. CONCLUSIONS: Our findings showed that tDCS treatment to DLPFC can reduce alcohol craving. These findings extend the results of previous studies using noninvasive brain stimulation to reduce craving in humans. Given the relatively rapid suppressive effect of tDCS and the highly fluctuating nature of alcohol craving, this technique may prove to be a valuable treatment strategy within the clinical setting.
Merabet LB, Wanye S. Eye care in the developing world: how soon is now?. Optom Vis Sci. 2008;85 (7) :605-7.
Amedi A, Merabet LB, Camprodon J, Bermpohl F, Fox S, Ronen I, Kim D-S, Pascual-Leone A. Neural and behavioral correlates of drawing in an early blind painter: a case study. Brain Res. 2008;1242 :252-62.Abstract
Humans rely heavily on vision to identify objects in the world and can create mental representations of the objects they encounter. Objects can also be identified and mentally represented through haptic exploration. However, it is unclear whether prior visual experience is necessary to generate these internal representations. Subject EA, an early blind artist, provides insight into this question. Like other blind individuals, EA captures the external world by touch. However, he is also able to reveal his internal representations through highly detailed drawings that are unequivocally understandable by a sighted person. We employed fMRI to investigate the neural correlates associated with EA's ability to transform tactilely explored three-dimensional objects into drawings and contrasted these findings with a series of control conditions (e.g. nonsensical scribbling as a sensory-motor control). Activation during drawing (compared to scribbling) occurred in brain areas normally associated with vision, including the striate cortex along with frontal and parietal cortical regions. Some of these areas showed overlap when EA was asked to mentally imagine the pictures he had to draw (albeit to a lesser anatomical extent and signal magnitude). These results have important implications as regards our understanding of the ways in which tactile information can generate mental representations of shapes and scenes in the absence of normal visual development. Furthermore, these findings suggest the occipital cortex plays a key role in supporting mental representations even without prior visual experience.
Merabet LB, Hamilton R, Schlaug G, Swisher JD, Kiriakopoulos ET, Pitskel NB, Kauffman T, Pascual-Leone A. Rapid and reversible recruitment of early visual cortex for touch. PLoS One. 2008;3 (8) :e3046.Abstract
BACKGROUND: The loss of vision has been associated with enhanced performance in non-visual tasks such as tactile discrimination and sound localization. Current evidence suggests that these functional gains are linked to the recruitment of the occipital visual cortex for non-visual processing, but the neurophysiological mechanisms underlying these crossmodal changes remain uncertain. One possible explanation is that visual deprivation is associated with an unmasking of non-visual input into visual cortex. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the effect of sudden, complete and prolonged visual deprivation (five days) in normally sighted adult individuals while they were immersed in an intensive tactile training program. Following the five-day period, blindfolded subjects performed better on a Braille character discrimination task. In the blindfold group, serial fMRI scans revealed an increase in BOLD signal within the occipital cortex in response to tactile stimulation after five days of complete visual deprivation. This increase in signal was no longer present 24 hours after blindfold removal. Finally, reversible disruption of occipital cortex function on the fifth day (by repetitive transcranial magnetic stimulation; rTMS) impaired Braille character recognition ability in the blindfold group but not in non-blindfolded controls. This disruptive effect was no longer evident once the blindfold had been removed for 24 hours. CONCLUSIONS/SIGNIFICANCE: Overall, our findings suggest that sudden and complete visual deprivation in normally sighted individuals can lead to profound, but rapidly reversible, neuroplastic changes by which the occipital cortex becomes engaged in processing of non-visual information. The speed and dynamic nature of the observed changes suggests that normally inhibited or masked functions in the sighted are revealed by visual loss. The unmasking of pre-existing connections and shifts in connectivity represent rapid, early plastic changes, which presumably can lead, if sustained and reinforced, to slower developing, but more permanent structural changes, such as the establishment of new neural connections in the blind.
Wanye S, Merabet LB. Eye care in the developing world: how soon is now?. Optometry and vision science : official publication of the American Academy of Optometry. 2008;85 :605-7. Publisher's VersionAbstract
n/a
Pitskel NB, Kauffman T, Pascual-Leone A, Kiriakopoulos ET, Swisher JD, Hamilton R, Schlaug G, Merabet LB. Rapid and reversible recruitment of early visual cortex for touch. PloS one. 2008;3 :e3046. Publisher's VersionAbstract

BACKGROUND: The loss of vision has been associated with enhanced performance in non-visual tasks such as tactile discrimination and sound localization. Current evidence suggests that these functional gains are linked to the recruitment of the occipital visual cortex for non-visual processing, but the neurophysiological mechanisms underlying these crossmodal changes remain uncertain. One possible explanation is that visual deprivation is associated with an unmasking of non-visual input into visual cortex. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the effect of sudden, complete and prolonged visual deprivation (five days) in normally sighted adult individuals while they were immersed in an intensive tactile training program. Following the five-day period, blindfolded subjects performed better on a Braille character discrimination task. In the blindfold group, serial fMRI scans revealed an increase in BOLD signal within the occipital cortex in response to tactile stimulation after five days of complete visual deprivation. This increase in signal was no longer present 24 hours after blindfold removal. Finally, reversible disruption of occipital cortex function on the fifth day (by repetitive transcranial magnetic stimulation; rTMS) impaired Braille character recognition ability in the blindfold group but not in non-blindfolded controls. This disruptive effect was no longer evident once the blindfold had been removed for 24 hours. CONCLUSIONS/SIGNIFICANCE: Overall, our findings suggest that sudden and complete visual deprivation in normally sighted individuals can lead to profound, but rapidly reversible, neuroplastic changes by which the occipital cortex becomes engaged in processing of non-visual information. The speed and dynamic nature of the observed changes suggests that normally inhibited or masked functions in the sighted are revealed by visual loss. The unmasking of pre-existing connections and shifts in connectivity represent rapid, early plastic changes, which presumably can lead, if sustained and reinforced, to slower developing, but more permanent structural changes, such as the establishment of new neural connections in the blind.

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