Publications

2008
Vecchi T, Bhatt E, Merabet LB, Cattaneo Z. Effects of complete monocular deprivation in visuo-spatial memory. Brain research bulletin. 2008;77 :112-6. Publisher's VersionAbstract

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.

Vecchi T, Pece A, Merabet LB, Bhatt E, Cattaneo Z. The influence of reduced visual acuity on age-related decline in spatial working memory: an investigation. Neuropsychology, development, and cognition. Section B, Aging, neuropsychology and cognition. 2008;15 :687-702. Publisher's VersionAbstract

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.

Bauer M, Heinz A, Schlaug G, Northoff G, Schlagenhauf F, Wrase J, Pascual-Leone A, Amedi A, Merabet LB, Fregni F, et al. Novelty seeking modulates medial prefrontal activity during the anticipation of emotional stimuli. Psychiatry research. 2008;164 :81-5. Publisher's VersionAbstract

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.

Pascual-Leone A, Basaglia A, Fregni F, Mecca T, Merabet L, Sultani N, Fecteau S, Boggio PS. Prefrontal cortex modulation using transcranial DC stimulation reduces alcohol craving: a double-blind, sham-controlled study. Drug and alcohol dependence. 2008;92 :55-60. Publisher's VersionAbstract

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.

Ronen I, Kim DS, Pascual-Leone A, Fox S, Bermpohl F, Merabet LB, Camprodon J, Amedi A. Neural and behavioral correlates of drawing in an early blind painter: a case study. Brain research. 2008;1242 :252-62. Publisher's VersionAbstract

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.

2007
Merabet LB, Swisher JD, McMains SA, Halko MA, Amedi A, Pascual-Leone A, Somers DC. Combined activation and deactivation of visual cortex during tactile sensory processing. J Neurophysiol. 2007;97 (2) :1633-41.Abstract
The involvement of occipital cortex in sensory processing is not restricted solely to the visual modality. Tactile processing has been shown to modulate higher-order visual and multisensory integration areas in sighted as well as visually deprived subjects; however, the extent of involvement of early visual cortical areas remains unclear. To investigate this issue, we employed functional magnetic resonance imaging in normally sighted, briefly blindfolded subjects with well-defined visuotopic borders as they tactually explored and rated raised-dot patterns. Tactile task performance resulted in significant activation in primary visual cortex (V1) and deactivation of extrastriate cortical regions V2, V3, V3A, and hV4 with greater deactivation in dorsal subregions and higher visual areas. These results suggest that tactile processing affects occipital cortex via two distinct pathways: a suppressive top-down pathway descending through the visual cortical hierarchy and an excitatory pathway arising from outside the visual cortical hierarchy that drives area V1 directly.
Merabet LB, Rizzo JF, Pascual-Leone A, Fernandez E. 'Who is the ideal candidate?': decisions and issues relating to visual neuroprosthesis development, patient testing and neuroplasticity. J Neural Eng. 2007;4 (1) :S130-5.Abstract
Appropriate delivery of electrical stimulation to intact visual structures can evoke patterned sensations of light in individuals who have been blind for many years. This pivotal finding has lent credibility to the concept of restoring functional vision by artificial means. As numerous groups worldwide pursue human clinical testing with visual prosthetic devices, it is becoming increasingly clear that there remains a considerable gap between the challenges of prosthetic device development and the rehabilitative strategies needed to implement this new technology in patients. An important area of future work will be the development of appropriate pre- and post-implantation measures of performance and establishing candidate selection criteria in order to quantify technical advances, guide future device design and optimize therapeutic success. We propose that the selection of an 'ideal' candidate should also be considered within the context of the variable neuroplastic changes that follow vision loss. Specifically, an understanding of the adaptive and compensatory changes that occur within the brain could assist in guiding the development of post-implantation rehabilitative strategies and optimize behavioral outcomes.
Cattoir V, Merabet L, Legrand P, Soussy C-J, Leclercq R. Emergence of a Streptococcus pneumoniae isolate resistant to streptogramins by mutation in ribosomal protein L22 during pristinamycin therapy of pneumococcal pneumonia. J Antimicrob Chemother. 2007;59 (5) :1010-2.Abstract
OBJECTIVES: The aim of this study was to characterize the mechanism of resistance to macrolides and streptogramins of a Streptococcus pneumoniae strain isolated from blood cultures in an 80-year-old patient suffering from severe pneumonia unsuccessfully treated with pristinamycin. METHODS: Resistance genes erm(B) and mef(A) were searched for by PCR. Portions of genes for domains V and II of the 23S rRNA (rrl) and genes for ribosomal proteins L4 (rplD) and L22 (rplV) were amplified by PCR from total genomic DNA and sequenced. RESULTS: Resistance genes erm(B) and mef(A) were not detected. Only mutation in the rplV gene encoding ribosomal protein L22 was detected. The strain contained a six amino acid insertion ((107)KRTAHI(108)) in the C-terminus of the ribosomal protein L22. CONCLUSIONS: This is the first report of emergence of a pneumococcus resistant to streptogramins by mutation in ribosomal protein L22 during treatment with pristinamycin.
Romei V, Murray MM, Merabet LB, Thut G. Occipital transcranial magnetic stimulation has opposing effects on visual and auditory stimulus detection: implications for multisensory interactions. J Neurosci. 2007;27 (43) :11465-72.Abstract
Multisensory interactions occur early in time and in low-level cortical areas, including primary cortices. To test current models of early auditory-visual (AV) convergence in unisensory visual brain areas, we studied the effect of transcranial magnetic stimulation (TMS) of visual cortex on behavioral responses to unisensory (auditory or visual) or multisensory (simultaneous auditory-visual) stimulus presentation. Single-pulse TMS was applied over the occipital pole at short delays (30-150 ms) after external stimulus onset. Relative to TMS over a control site, reactions times (RTs) to unisensory visual stimuli were prolonged by TMS at 60-75 ms poststimulus onset (visual suppression effect), confirming stimulation of functional visual cortex. Conversely, RTs to unisensory auditory stimuli were significantly shortened when visual cortex was stimulated by TMS at the same delays (beneficial interaction effect of auditory stimulation and occipital TMS). No TMS-effect on RTs was observed for AV stimulation. The beneficial interaction effect of combined unisensory auditory and TMS-induced visual cortex stimulation matched and was correlated with the RT-facilitation after external multisensory AV stimulation without TMS, suggestive of multisensory interactions between the stimulus-evoked auditory and TMS-induced visual cortex activities. A follow-up experiment showed that auditory input enhances excitability within visual cortex itself (using phosphene-induction via TMS as a measure) over a similarly early time-window (75-120 ms). The collective data support a mechanism of early auditory-visual interactions that is mediated by auditory-driven sensitivity changes in visual neurons that coincide in time with the initial volleys of visual input.
Amedi A, Stern WM, Camprodon JA, Bermpohl F, Merabet L, Rotman S, Hemond C, Meijer P, Pascual-Leone A. Shape conveyed by visual-to-auditory sensory substitution activates the lateral occipital complex. Nat Neurosci. 2007;10 (6) :687-9.Abstract
The lateral-occipital tactile-visual area (LOtv) is activated when objects are recognized by vision or touch. We report here that the LOtv is also activated in sighted and blind humans who recognize objects by extracting shape information from visual-to-auditory sensory substitution soundscapes. Recognizing objects by their typical sounds or learning to associate specific soundscapes with specific objects do not activate this region. This suggests that LOtv is driven by the presence of shape information.
Pitskel NB, Merabet LB, Ramos-Estebanez C, Kauffman T, Pascual-Leone A. Time-dependent changes in cortical excitability after prolonged visual deprivation. Neuroreport. 2007;18 (16) :1703-7.Abstract
Transcranial magnetic stimulation applied to the occipital cortex can elicit phosphenes. Changes in the phosphene threshold provide a measure of visual cortex excitability. Phosphene threshold was measured in participants blindfolded for five consecutive days to assess the effects of prolonged visual deprivation on visual cortical excitability. After 48 h of blindfolding, an acute decrease in phosphene threshold was observed, followed by a significant increase by day 5. Phosphene threshold returned to preblindfold levels within 2 h of light re-exposure. Thus, light deprivation is characterized by a transient increase in visual cortical excitability, followed by a sustained decrease in visual cortex excitability that quickly returns to baseline levels after re-exposure to light.
Ramos-Estebanez C, Merabet LB, Machii K, Fregni F, Thut G, Wagner TA, Romei V, Amedi A, Pascual-Leone A. Visual phosphene perception modulated by subthreshold crossmodal sensory stimulation. J Neurosci. 2007;27 (15) :4178-81.Abstract
Crossmodal sensory interactions serve to integrate behaviorally relevant sensory stimuli. In this study, we investigated the effect of modulating crossmodal interactions between visual and somatosensory stimuli that in isolation do not reach perceptual awareness. When a subthreshold somatosensory stimulus was delivered within close spatiotemporal congruency to the expected site of perception of a phosphene, a subthreshold transcranial magnetic stimulation pulse delivered to the occipital cortex evoked a visual percept. The results suggest that under subthreshold conditions of visual and somatosensory stimulation, crossmodal interactions presented in a spatially and temporally specific manner can sum up to become behaviorally significant. These interactions may reflect an underlying anatomical connectivity and become further enhanced by attention modulation mechanisms.
Swisher JD, Halko MA, Merabet LB, McMains SA, Somers DC. Visual topography of human intraparietal sulcus. J Neurosci. 2007;27 (20) :5326-37.Abstract
Human parietal cortex is implicated in a wide variety of sensory and cognitive functions, yet its precise organization remains unclear. Visual field maps provide a potential structural basis for descriptions of functional organization. Here, we detail the topography of a series of five maps of the contralateral visual hemifield within human posterior parietal cortex. These maps are located along the medial bank of the intraparietal sulcus (IPS) and are revealed by direct visual stimulation during functional magnetic resonance imaging, allowing these parietal regions to be routinely and reliably identified simultaneously with occipital visual areas. Two of these maps (IPS3 and IPS4) are novel, whereas two others (IPS1 and IPS2) have previously been revealed only by higher-order cognitive tasks. Area V7, a previously identified visual map, is observed to lie within posterior IPS and to share a foveal representation with IPS1. These parietal maps are reliably observed across scan sessions; however, their precise topography varies between individuals. The multimodal organization of posterior IPS mirrors this variability in visual topography, with complementary tactile activations found immediately adjacent to the visual maps both medially and laterally. These visual maps may provide a practical framework in which to characterize the functional organization of human IPS.
Somers DC, McMains SA, Merabet LB, Halko MA, Swisher JD. Visual topography of human intraparietal sulcus. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2007;27 :5326-37. Publisher's VersionAbstract

Human parietal cortex is implicated in a wide variety of sensory and cognitive functions, yet its precise organization remains unclear. Visual field maps provide a potential structural basis for descriptions of functional organization. Here, we detail the topography of a series of five maps of the contralateral visual hemifield within human posterior parietal cortex. These maps are located along the medial bank of the intraparietal sulcus (IPS) and are revealed by direct visual stimulation during functional magnetic resonance imaging, allowing these parietal regions to be routinely and reliably identified simultaneously with occipital visual areas. Two of these maps (IPS3 and IPS4) are novel, whereas two others (IPS1 and IPS2) have previously been revealed only by higher-order cognitive tasks. Area V7, a previously identified visual map, is observed to lie within posterior IPS and to share a foveal representation with IPS1. These parietal maps are reliably observed across scan sessions; however, their precise topography varies between individuals. The multimodal organization of posterior IPS mirrors this variability in visual topography, with complementary tactile activations found immediately adjacent to the visual maps both medially and laterally. These visual maps may provide a practical framework in which to characterize the functional organization of human IPS.

Thut G, Merabet LB, Murray MM, Romei V. Occipital transcranial magnetic stimulation has opposing effects on visual and auditory stimulus detection: implications for multisensory interactions. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2007;27 :11465-72. Publisher's VersionAbstract

Multisensory interactions occur early in time and in low-level cortical areas, including primary cortices. To test current models of early auditory-visual (AV) convergence in unisensory visual brain areas, we studied the effect of transcranial magnetic stimulation (TMS) of visual cortex on behavioral responses to unisensory (auditory or visual) or multisensory (simultaneous auditory-visual) stimulus presentation. Single-pulse TMS was applied over the occipital pole at short delays (30-150 ms) after external stimulus onset. Relative to TMS over a control site, reactions times (RTs) to unisensory visual stimuli were prolonged by TMS at 60-75 ms poststimulus onset (visual suppression effect), confirming stimulation of functional visual cortex. Conversely, RTs to unisensory auditory stimuli were significantly shortened when visual cortex was stimulated by TMS at the same delays (beneficial interaction effect of auditory stimulation and occipital TMS). No TMS-effect on RTs was observed for AV stimulation. The beneficial interaction effect of combined unisensory auditory and TMS-induced visual cortex stimulation matched and was correlated with the RT-facilitation after external multisensory AV stimulation without TMS, suggestive of multisensory interactions between the stimulus-evoked auditory and TMS-induced visual cortex activities. A follow-up experiment showed that auditory input enhances excitability within visual cortex itself (using phosphene-induction via TMS as a measure) over a similarly early time-window (75-120 ms). The collective data support a mechanism of early auditory-visual interactions that is mediated by auditory-driven sensitivity changes in visual neurons that coincide in time with the initial volleys of visual input.

Romei V, Amedi A, Pascual-Leone A, Wagner TA, Thut G, Merabet LB, Machii K, Fregni F, Ramos-Estebanez C. Visual phosphene perception modulated by subthreshold crossmodal sensory stimulation. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2007;27 :4178-81. Publisher's VersionAbstract

Crossmodal sensory interactions serve to integrate behaviorally relevant sensory stimuli. In this study, we investigated the effect of modulating crossmodal interactions between visual and somatosensory stimuli that in isolation do not reach perceptual awareness. When a subthreshold somatosensory stimulus was delivered within close spatiotemporal congruency to the expected site of perception of a phosphene, a subthreshold transcranial magnetic stimulation pulse delivered to the occipital cortex evoked a visual percept. The results suggest that under subthreshold conditions of visual and somatosensory stimulation, crossmodal interactions presented in a spatially and temporally specific manner can sum up to become behaviorally significant. These interactions may reflect an underlying anatomical connectivity and become further enhanced by attention modulation mechanisms.

Pascual-Leone A, Kauffman T, Ramos-Estebanez C, Merabet LB, Pitskel NB. Time-dependent changes in cortical excitability after prolonged visual deprivation. Neuroreport. 2007;18 :1703-7. Publisher's VersionAbstract

Transcranial magnetic stimulation applied to the occipital cortex can elicit phosphenes. Changes in the phosphene threshold provide a measure of visual cortex excitability. Phosphene threshold was measured in participants blindfolded for five consecutive days to assess the effects of prolonged visual deprivation on visual cortical excitability. After 48 h of blindfolding, an acute decrease in phosphene threshold was observed, followed by a significant increase by day 5. Phosphene threshold returned to preblindfold levels within 2 h of light re-exposure. Thus, light deprivation is characterized by a transient increase in visual cortical excitability, followed by a sustained decrease in visual cortex excitability that quickly returns to baseline levels after re-exposure to light.

Pascual-Leone A, Somers DC, Amedi A, Halko MA, Swisher JD, McMains SA, Merabet LB. Combined activation and deactivation of visual cortex during tactile sensory processing. Journal of neurophysiology. 2007;97 :1633-41. Publisher's VersionAbstract

The involvement of occipital cortex in sensory processing is not restricted solely to the visual modality. Tactile processing has been shown to modulate higher-order visual and multisensory integration areas in sighted as well as visually deprived subjects; however, the extent of involvement of early visual cortical areas remains unclear. To investigate this issue, we employed functional magnetic resonance imaging in normally sighted, briefly blindfolded subjects with well-defined visuotopic borders as they tactually explored and rated raised-dot patterns. Tactile task performance resulted in significant activation in primary visual cortex (V1) and deactivation of extrastriate cortical regions V2, V3, V3A, and hV4 with greater deactivation in dorsal subregions and higher visual areas. These results suggest that tactile processing affects occipital cortex via two distinct pathways: a suppressive top-down pathway descending through the visual cortical hierarchy and an excitatory pathway arising from outside the visual cortical hierarchy that drives area V1 directly.

Fernandez E, Pascual-Leone A, Rizzo, J. F. 3rd, Merabet LB. 'Who is the ideal candidate?': decisions and issues relating to visual neuroprosthesis development, patient testing and neuroplasticity. Journal of neural engineering. 2007;4 :S130-5. Publisher's VersionAbstract

Appropriate delivery of electrical stimulation to intact visual structures can evoke patterned sensations of light in individuals who have been blind for many years. This pivotal finding has lent credibility to the concept of restoring functional vision by artificial means. As numerous groups worldwide pursue human clinical testing with visual prosthetic devices, it is becoming increasingly clear that there remains a considerable gap between the challenges of prosthetic device development and the rehabilitative strategies needed to implement this new technology in patients. An important area of future work will be the development of appropriate pre- and post-implantation measures of performance and establishing candidate selection criteria in order to quantify technical advances, guide future device design and optimize therapeutic success. We propose that the selection of an 'ideal' candidate should also be considered within the context of the variable neuroplastic changes that follow vision loss. Specifically, an understanding of the adaptive and compensatory changes that occur within the brain could assist in guiding the development of post-implantation rehabilitative strategies and optimize behavioral outcomes.

Hemond C, Meijer P, Pascual-Leone A, Rotman S, Merabet L, Stern WM, Camprodon JA, Bermpohl F, Amedi A. Shape conveyed by visual-to-auditory sensory substitution activates the lateral occipital complex. Nature neuroscience. 2007;10 :687-9. Publisher's VersionAbstract

The lateral-occipital tactile-visual area (LOtv) is activated when objects are recognized by vision or touch. We report here that the LOtv is also activated in sighted and blind humans who recognize objects by extracting shape information from visual-to-auditory sensory substitution soundscapes. Recognizing objects by their typical sounds or learning to associate specific soundscapes with specific objects do not activate this region. This suggests that LOtv is driven by the presence of shape information.

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