The Role of the Thalamus in Post-Traumatic Stress Disorder.

Post-traumatic stress disorder (PTSD) has a high lifetime prevalence and is one of the more serious challenges in mental health care. Fear-conditioned learning involving the amygdala has been thought to be one of the main causative factors; however, recent studies have reported abnormalities in the thalamus of PTSD patients, which may explain the mechanism of interventions such as eye movement desensitization and reprocessing (EMDR). Therefore, I conducted a miniature literature review on the potential contribution of the thalamus to the pathogenesis of PTSD and the validation of therapeutic approaches. As a result, we noticed the importance of the retinotectal pathway (superior colliculus-pulvinar-amygdala connection) and discussed therapeutic indicators.

V1 Projection Zone Signals in Human Macular Degeneration Depend on Task Despite Absence of Visual Stimulus.

Identifying the plastic and stable components of the visual cortex after retinal loss is an important topic in visual neuroscience and neuro-ophthalmology.1-5 Humans with juvenile macular degeneration (JMD) show significant blood-oxygen-level-dependent (BOLD) responses in the primary visual area (V1) lesion projection zone (LPZ),6 despite the absence of the feedforward signals from the degenerated retina. Our previous study7 reported that V1 LPZ responds to full-field visual stimuli during the one-back task (OBT), not during passive viewing, suggesting the involvement of task-related feedback signals. Aiming to clarify whether visual inputs to the intact retina are necessary for the LPZ responses, here, we measured BOLD responses to tactile and auditory stimuli for both JMD patients and control participants with and without OBT. Participants were instructed to close their eyes during the experiment for the purpose of eliminating retinal inputs. Without OBT, no V1 responses were detected in both groups of participants. With OBT, to the contrary, both stimuli caused substantial V1 responses in JMD patients, but not controls. Furthermore, we also found that the task-dependent activity in V1 LPZ became less pronounced when JMD patients opened their eyes, suggesting that task-related feedback signals can be partially suppressed by residual feedforward signals. Modality-independent V1 LPZ responses only in the task condition suggest that V1 LPZ responses reflect task-related feedback signals rather than reorganized feedforward visual inputs.

The Dynamics of Functional Brain Networks Associated With Depressive Symptoms in a Nonclinical Sample.

Brain function depends on the flexible and dynamic coordination of functional subsystems within distributed neural networks operating on multiple scales. Recent progress has been made in the characterization of functional connectivity (FC) at the whole-brain scale from a dynamic, rather than static, perspective, but its validity for cognitive sciences remains under debate. Here, we analyzed brain activity recorded with functional Magnetic Resonance Imaging from 71 healthy participants evaluated for depressive symptoms after a relationship breakup based on the conventional Major Depression Inventory (MDI). We compared both static and dynamic FC patterns between participants reporting high and low depressive symptoms. Between-group differences in static FC were estimated using a standard pipeline for network-based statistic (NBS). Additionally, FC was analyzed from a dynamic perspective by characterizing the occupancy, lifetime, and transition profiles of recurrent FC patterns. Recurrent FC patterns were defined by clustering the BOLD phase-locking patterns obtained using leading eigenvector dynamics analysis (LEiDA). NBS analysis revealed a brain subsystem exhibiting significantly lower within-subsystem correlation values in more depressed participants (high MDI). This subsystem predominantly comprised connections between regions of the default mode network (i.e., precuneus) and regions outside this network. On the other hand, LEiDA results showed that high MDI participants engaged more in a state connecting regions of the default mode, memory retrieval, and frontoparietal network (p-FDR = 0.012); and less in a state connecting mostly the visual and dorsal attention systems (p-FDR = 0.004). Although both our analyses on static and dynamic FC implicate the role of the precuneus in depressive symptoms, only including the temporal evolution of BOLD FC helped to disentangle over time the distinct configurations in which this region plays a role. This finding further indicates that a holistic understanding of brain function can only be gleaned if the temporal dynamics of FC is included.

Unique Features of Subcortical Circuits in a Macaque Model of Congenital Blindness.

There is an extensive modification of the functional organization of the brain in the congenital blind human, although there is little understanding of the structural underpinnings of these changes. The visual system of macaque has been extensively characterized both anatomically and functionally. We have taken advantage of this to examine the influence of congenital blindness in a macaque model of developmental anophthalmia. Developmental anophthalmia in macaque effectively removes the normal influence of the thalamus on cortical development leading to an induced "hybrid cortex (HC)" combining features of primary visual and extrastriate cortex. Here we show that retrograde tracers injected in early visual areas, including HC, reveal a drastic reduction of cortical projections of the reduced lateral geniculate nucleus. In addition, there is an important expansion of projections from the pulvinar complex to the HC, compared to the controls. These findings show that the functional consequences of congenital blindness need to be considered in terms of both modifications of the interareal cortical network and the ascending visual pathways.

Amblyopia Affects the ON Visual Pathway More than the OFF.

Visual information reaches the cerebral cortex through parallel ON and OFF pathways that signal the presence of light and dark stimuli in visual scenes. We have previously demonstrated that optical blur reduces visual salience more for light than dark stimuli because it removes the high spatial frequencies from the stimulus, and low spatial frequencies drive weaker ON than OFF cortical responses. Therefore, we hypothesized that sustained optical blur during brain development should weaken ON cortical pathways more than OFF, increasing the dominance of darks in visual perception. Here we provide support for this hypothesis in humans with anisometropic amblyopia who suffered sustained optical blur early after birth in one of the eyes. In addition, we show that the dark dominance in visual perception also increases in strabismic amblyopes that have their vision to high spatial frequencies reduced by mechanisms not associated with optical blur. Together, we show that amblyopia increases visual dark dominance by 3-10 times and that the increase in dark dominance is strongly correlated with amblyopia severity. These results can be replicated with a computational model that uses greater luminance/response saturation in ON than OFF pathways and, as a consequence, reduces more ON than OFF cortical responses to stimuli with low spatial frequencies. We conclude that amblyopia affects the ON cortical pathway more than the OFF, a finding that could have implications for future amblyopia treatments.SIGNIFICANCE STATEMENT Amblyopia is a loss of vision that affects 2-5% of children across the world and originates from a deficit in visual cortical circuitry. Current models assume that amblyopia affects similarly ON and OFF visual pathways, which signal light and dark features in visual scenes. Against this current belief, here we demonstrate that amblyopia affects the ON visual pathway more than the OFF, a finding that could have implications for new amblyopia treatments targeted at strengthening a weak ON visual pathway.

Advanced visual network and cerebellar hyperresponsiveness to trigeminal nociception in migraine with aura.

BACKGROUND: Despite the growing body of advanced studies investigating the neuronal correlates of pain processing in patients with migraine without aura (MwoA), only few similar studies have been conducted in patients with migraine with aura (MwA). Therefore, we aimed to explore the functional brain response to trigeminal noxious heat stimulation in patients with MwA. METHODS: Seventeen patients with MwA and 15 age- and sex-matched healthy controls (HC) underwent whole-brain blood oxygen level-dependent (BOLD) fMRI during trigeminal noxious heat stimulation. To examine the specificity of any observed differences between patients with MwA and HC, the functional response of neural pathways to trigeminal noxious heat stimulation in patients with MwA was compared with 18 patients with MwoA. Secondary analyses investigated the correlations between BOLD signal changes and clinical parameters of migraine severity. RESULTS: We observed a robust cortical and subcortical pattern of BOLD response to trigeminal noxious heat stimulation across all participants. Patients with MwA showed a significantly increased activity in higher cortical areas known to be part of a distributed network involved in advanced visual processing, including lingual gyrus, inferior parietal lobule, inferior frontal gyrus and medial frontal gyrus. Moreover, a significantly greater cerebellar activation was observed in patients with MwA when compared with both patients with MwA and HC. Interestingly, no correlations were found between migraine severity parameters and magnitude of BOLD response in patients with MwA. CONCLUSION: Our findings, characterized by abnormal visual pathway response to trigeminal noxious heat stimulation, support the role of a functional integration between visual and trigeminal pain networks in the pathophysiological mechanisms underlying migraine with aura. Moreover, they expand the concept of "neurolimbic-pain network" as a model of MwoA including both limbic dysfunction and cortical dys-excitability. Indeed, we suggest a model of "neurolimbic-visual-pain network" in MwA patients, characterized by dysfunctional correlations between pain-modulating circuits not only with the cortical limbic areas but with advanced visual areas as well. Furthermore, the abnormal cerebellar response to trigeminal noxious heat stimulation may suggest a dysfunctional cerebellar inhibitory control on thalamic sensory gating, impinging on the advanced visual processing cortical areas in patients with MwA.

Reconfiguration of Dynamic Functional Connectivity in Sensory and Perceptual System in Schizophrenia.

Schizophrenia is thought as a self-disorder with dysfunctional brain connectivity. This self-disorder is often attributed to high-order cognitive impairment. Yet due to the frequent report of sensorial and perceptual deficits, it has been hypothesized that self-disorder in schizophrenia is dysfunctional communication between sensory and cognitive processes. To further verify this assumption, the present study comprehensively examined dynamic reconfigurations of resting-state functional connectivity (rsFC) in schizophrenia at voxel level, region level, and network levels (102 patients vs. 124 controls). We found patients who show consistently increased rsFC variability in sensory and perceptual system, including visual network, sensorimotor network, attention network, and thalamus at all the three levels. However, decreased variability in high-order networks, such as default mode network and frontal-parietal network were only consistently observed at region and network levels. Taken together, these findings highlighted the rudimentary role of elevated instability of information communication in sensory and perceptual system and attenuated whole-brain integration of high-order network in schizophrenia, which provided novel neural evidence to support the hypothesis of disrupted perceptual and cognitive function in schizophrenia. The foci of effects also highlighted that targeting perceptual deficits can be regarded as the key to enhance our understanding of pathophysiology in schizophrenia and promote new treatment intervention.

Current understanding of photophobia, visual networks and headaches.

OBJECTIVE: To review clinical and pre-clinical evidence supporting the role of visual pathways, from the eye to the cortex, in the development of photophobia in headache disorders. BACKGROUND: Photophobia is a poorly understood light-induced phenomenon that emerges in a variety of neurological and ophthalmological conditions. Over the years, multiple mechanisms have been proposed to explain its causes; however, scarce research and lack of systematic assessment of photophobia in patients has made the search for answers quite challenging. In the field of headaches, significant progress has been made recently on how specific visual networks contribute to photophobia features such as light-induced intensification of headache, increased perception of brightness and visual discomfort, which are frequently experienced by migraineurs. Such progress improved our understanding of the phenomenon and points to abnormal processing of light by both cone/rod-mediated image-forming and melanopsin-mediated non-image-forming visual pathways, and the consequential transfer of photic signals to multiple brain regions involved in sensory, autonomic and emotional regulation. CONCLUSION: Photophobia phenotype is diverse, and the relative contribution of visual, trigeminal and autonomic systems may depend on the disease it emerges from. In migraine, photophobia could result from photic activation of retina-driven pathways involved in the regulation of homeostasis, making its association with headache more complex than previously thought.

Altered Structural Connectivity of the Left Visual Thalamus in Developmental Dyslexia.

Developmental dyslexia is a highly prevalent reading disorder affecting about 5%-10% of children [1]. It is characterized by slow and/or inaccurate word recognition skills as well as by poor spelling and decoding abilities [2]. Partly due to technical challenges with investigating subcortical sensory structures, current research on dyslexia in humans by and large focuses on the cerebral cortex [3-7]. These studies found that dyslexia is typically associated with functional and structural alterations of a distributed left-hemispheric cerebral cortex network (e.g., [8, 9]). However, findings from animal models and post mortem studies in humans suggest that dyslexia might also be associated with structural alterations in subcortical sensory pathways [10-14] (reviewed in [7]). Whether these alterations also exist in dyslexia in vivo and how they relate to dyslexia symptoms is currently unknown. Here, we used ultra-high-resolution structural magnetic resonance imaging (MRI), diffusion MRI, and probabilistic tractography to investigate the structural connections of the visual sensory pathway in dyslexia in vivo. We discovered that individuals with dyslexia have reduced structural connections in the direct pathway between the left visual thalamus (lateral geniculate nucleus [LGN]) and left middle temporal area V5/MT, but not between the left LGN and left primary visual cortex. In addition, left V5/MT-LGN connectivity strength correlated with rapid naming abilities-a key deficit in dyslexia [15]. These findings provide the first evidence of specific structural alterations in the connections between the sensory thalamus and cortex in developmental dyslexia. The results challenge current standard models and provide novel evidence for the importance of cortico-thalamic interactions in explaining dyslexia.

Reorganization of neural systems mediating peripheral visual selective attention in the deaf: An optical imaging study.

Theories of brain plasticity propose that, in the absence of input from the preferred sensory modality, some specialized brain areas may be recruited when processing information from other modalities, which may result in improved performance. The Useful Field of View task has previously been used to demonstrate that early deafness positively impacts peripheral visual attention. The current study sought to determine the neural changes associated with those deafness-related enhancements in visual performance. Based on previous findings, we hypothesized that recruitment of posterior portions of Brodmann area 22, a brain region most commonly associated with auditory processing, would be correlated with peripheral selective attention as measured using the Useful Field of View task. We report data from severe to profoundly deaf adults and normal-hearing controls who performed the Useful Field of View task while cortical activity was recorded using the event-related optical signal. Behavioral performance, obtained in a separate session, showed that deaf subjects had lower thresholds (i.e., better performance) on the Useful Field of View task. The event-related optical data indicated greater activity for the deaf adults than for the normal-hearing controls during the task in the posterior portion of Brodmann area 22 in the right hemisphere. Furthermore, the behavioral thresholds correlated significantly with this neural activity. This work provides further support for the hypothesis that cross-modal plasticity in deaf individuals appears in higher-order auditory cortices, whereas no similar evidence was obtained for primary auditory areas. It is also the only neuroimaging study to date that has linked deaf-related changes in the right temporal lobe to visual task performance outside of the imaging environment. The event-related optical signal is a valuable technique for studying cross-modal plasticity in deaf humans. The non-invasive and relatively quiet characteristics of this technique have great potential utility in research with clinical populations such as deaf children and adults who have received cochlear or auditory brainstem implants.

Migraine photophobia originating in cone-driven retinal pathways.

Migraine headache is uniquely exacerbated by light. Using psychophysical assessments in patients with normal eyesight we found that green light exacerbates migraine headache significantly less than white, blue, amber or red lights. To delineate mechanisms, we used electroretinography and visual evoked potential recording in patients, and multi-unit recording of dura- and light-sensitive thalamic neurons in rats to show that green activates cone-driven retinal pathways to a lesser extent than white, blue and red; that thalamic neurons are most responsive to blue and least responsive to green; and that cortical responses to green are significantly smaller than those generated by blue, amber and red lights. These findings suggest that patients' experience with colour and migraine photophobia could originate in cone-driven retinal pathways, fine-tuned in relay thalamic neurons outside the main visual pathway, and preserved by the cortex. Additionally, the findings provide substrate for the soothing effects of green light.

Visual snow: A thalamocortical dysrhythmia of the visual pathway?

In this paper we review the visual snow (VS) characteristics of a case cohort of 32 patients. History of symptoms and associated co-morbidities, ophthalmic examination, previous investigations and the results of intuitive colourimetry were collected and reviewed. VS symptoms follow a stereotypical description and are strongly associated with palinopsia, migraine and tinnitus, but also tremor. The condition is a chronic one and often results in misdiagnosis with psychiatric disorders or malingering. Colour filters, particularly in the yellow-blue colour spectrum, subjectively reduced symptoms of VS. There is neurobiological evidence for the syndrome of VS that links it with other disorders of visual and sensory processing such as migraine and tinnitus. Colour filters in the blue-yellow spectrum may alter the koniocellular pathway processing, which has a regulatory effect on background electroencephalographic rhythms, and may add weight to the hypothesis that VS is a thalamocortical dysrhythmia of the visual pathway.

Thalamic alterations in preterm neonates and their relation to ventral striatum disturbances revealed by a combined shape and pose analysis.

Finding the neuroanatomical correlates of prematurity is vital to understanding which structures are affected, and to designing efficient prevention and treatment strategies. Converging results reveal that thalamic abnormalities are important indicators of prematurity. However, little is known about the localization of the abnormalities within the subnuclei of the thalamus, or on the association of altered thalamic development with other deep gray matter disturbances. Here, we aim to investigate the effect of prematurity on the thalamus and the putamen in the neonatal brain, and further investigate the associated abnormalities between these two structures. Using brain structural magnetic resonance imaging, we perform a novel combined shape and pose analysis of the thalamus and putamen between 17 preterm (41.12 ± 5.08 weeks) and 19 term-born (45.51 ± 5.40 weeks) neonates at term equivalent age. We also perform a set of correlation analyses between the thalamus and the putamen, based on the surface and pose results. We locate significant alterations on specific surface regions such as the anterior and ventral anterior (VA) thalamic nuclei, and significant relative pose changes of the left thalamus and the right putamen. In addition, we detect significant association between the thalamus and the putamen for both surface and pose parameters. The regions that are significantly associated include the VA, and the anterior and inferior putamen. We detect statistically significant surface deformations and pose changes on the thalamus and putamen, and for the first time, demonstrate the feasibility of using relative pose parameters as indicators for prematurity in neonates. Our methods show that regional abnormalities of the thalamus are associated with alterations of the putamen, possibly due to disturbed development of shared pre-frontal connectivity. More specifically, the significantly correlated regions in these two structures point to frontal-subcortical pathways including the dorsolateral prefrontal-subcortical circuit, the lateral orbitofrontal-subcortical circuit, the motor circuit, and the oculomotor circuit. These findings reveal new insight into potential subcortical structural covariates for poor neurodevelopmental outcomes in the preterm population.

Reading in the dark: neural correlates and cross-modal plasticity for learning to read entire words without visual experience.

Cognitive neuroscience has long attempted to determine the ways in which cortical selectivity develops, and the impact of nature vs. nurture on it. Congenital blindness (CB) offers a unique opportunity to test this question as the brains of blind individuals develop without visual experience. Here we approach this question through the reading network. Several areas in the visual cortex have been implicated as part of the reading network, and one of the main ones among them is the VWFA, which is selective to the form of letters and words. But what happens in the CB brain? On the one hand, it has been shown that cross-modal plasticity leads to the recruitment of occipital areas, including the VWFA, for linguistic tasks. On the other hand, we have recently demonstrated VWFA activity for letters in contrast to other visual categories when the information is provided via other senses such as touch or audition. Which of these tasks is more dominant? By which mechanism does the CB brain process reading? Using fMRI and visual-to-auditory sensory substitution which transfers the topographical features of the letters we compare reading with semantic and scrambled conditions in a group of CB. We found activation in early auditory and visual cortices during the early processing phase (letter), while the later phase (word) showed VWFA and bilateral dorsal-intraparietal activations for words. This further supports the notion that many visual regions in general, even early visual areas, also maintain a predilection for task processing even when the modality is variable and in spite of putative lifelong linguistic cross-modal plasticity. Furthermore, we find that the VWFA is recruited preferentially for letter and word form, while it was not recruited, and even exhibited deactivation, for an immediately subsequent semantic task suggesting that despite only short sensory substitution experience orthographic task processing can dominate semantic processing in the VWFA. On a wider scope, this implies that at least in some cases cross-modal plasticity which enables the recruitment of areas for new tasks may be dominated by sensory independent task specific activation.

Intracortical and Thalamocortical Connections of the Hand and Face Representations in Somatosensory Area 3b of Macaque Monkeys and Effects of Chronic Spinal Cord Injuries.

Brains of adult monkeys with chronic lesions of dorsal columns of spinal cord at cervical levels undergo large-scale reorganization. Reorganization results in expansion of intact chin inputs, which reactivate neurons in the deafferented hand representation in the primary somatosensory cortex (area 3b), ventroposterior nucleus of the thalamus and cuneate nucleus of the brainstem. A likely contributing mechanism for this large-scale plasticity is sprouting of axons across the hand-face border. Here we determined whether such sprouting takes place in area 3b. We first determined the extent of intrinsic corticocortical connectivity between the hand and the face representations in normal area 3b. Small amounts of neuroanatomical tracers were injected in these representations close to the electrophysiologically determined hand-face border. Locations of the labeled neurons were mapped with respect to the detailed electrophysiological somatotopic maps and histologically determined hand-face border revealed in sections of the flattened cortex stained for myelin. Results show that intracortical projections across the hand-face border are few. In monkeys with chronic unilateral lesions of the dorsal columns and expanded chin representation, connections across the hand-face border were not different compared with normal monkeys. Thalamocortical connections from the hand and face representations in the ventroposterior nucleus to area 3b also remained unaltered after injury. The results show that sprouting of intrinsic connections in area 3b or the thalamocortical inputs does not contribute to large-scale cortical plasticity. Significance statement: Long-term injuries to dorsal spinal cord in adult primates result in large-scale somatotopic reorganization due to which chin inputs expand into the deafferented hand region. Reorganization takes place in multiple cortical areas, and thalamic and medullary nuclei. To what extent this brain reorganization due to dorsal column injuries is related to axonal sprouting is not known. Here we show that reorganization of primary somatosensory area 3b is not accompanied with either an increase in intrinsic cortical connections between the hand and face representations, or any change in thalamocortical inputs to these areas. Axonal sprouting that causes reorganization likely takes place at subthalamic levels.

Developmental synergy between thalamic structure and interhemispheric connectivity in the visual system of preterm infants.

Thalamic structural co-variation with cortical regions has been demonstrated in preterm infants, but its relationship to cortical function and severity of non-cystic white matter injury (non-cystic WMI) is unclear. The relationship between thalamic morphology and both cortical network synchronization and cortical structural connectivity has not been established. We tested the hypothesis that in preterm neonates, thalamic volume would correlate with primary cortical visual function and microstructural integrity of cortico-cortical visual association pathways. A total of 80 term-equivalent preterm and 44 term-born infants underwent high-resolution structural imaging coupled with visual functional magnetic resonance imaging or diffusion tensor imaging. There was a strong correlation between thalamic volume and primary visual cortical activation in preterms with non-cystic WMI (r = 0.81, p-value = 0.001). Thalamic volume also correlated strongly with interhemispheric cortico-cortical connectivity (splenium) in preterm neonates with a relatively higher severity of non-cystic WMI (p-value < 0.001). In contrast, there was lower correlation between thalamic volume and intrahemispheric cortico-cortical connectivity, including the inferior longitudinal fasciculus and inferior frontal orbital fasciculus. This study shows distinct temporal overlap in the disruption of thalamo-cortical and interhemispheric cortico-cortical connectivity in preterm infants suggesting developmental synergy between thalamic morphology and the emergence of cortical networks in the last trimester.

Ophthalmology issues in schizophrenia.

Schizophrenia is a complex mental disorder associated with not only cognitive dysfunctions, such as memory and attention deficits, but also changes in basic sensory processing. Although most studies on schizophrenia have focused on disturbances in higher-order brain functions associated with the prefrontal cortex or frontal cortex, recent investigations have also reported abnormalities in low-level sensory processes, such as the visual system. At very early stages of the disease, schizophrenia patients frequently describe in detail symptoms of a disturbance in various aspects of visual perception that may lead to worse clinical symptoms and decrease in quality of life. Therefore, the aim of this review is to describe the various studies that have explored the visual issues in schizophrenia.

Retinal origin of electrically evoked potentials in response to transcorneal alternating current stimulation in the rat.

PURPOSE: Little is known about the physiological mechanisms underlying the reported therapeutic effects of transorbital alternating current stimulation (ACS) in vision restoration, or the origin of the recorded electrically evoked potentials (EEPs) during such stimulation. We examined the issue of EEP origin and electrode configuration for transorbital ACS and characterized the physiological responses to CS in different structures of the visual system. METHODS: We recorded visually evoked potentials (VEPs) and EEPs from the rat retina, visual thalamus, tectum, and visual cortex. The VEPs were evoked by light flashes and EEPs were evoked by electric stimuli delivered by two electrodes placed either together on the same eye or on the eyeball and in the neck. Electrically evoked potentials and VEPs were recorded before and after bilateral intraorbital injections of tetrodotoxin that blocked retinal ganglion cell activity. RESULTS: Tetrodotoxin abolished VEPs at all levels in the visual pathway, confirming successful blockage of ganglion cell activity. Tetrodotoxin also abolished EEPs and this effect was independent of the stimulating electrode configurations. CONCLUSIONS: Transorbital electrically evoked responses in the visual pathway, irrespective of reference electrode placement, are initiated by activation of the retina and not by passive conductance and direct activation of neurons in other visual structures. Thus, placement of stimulating electrodes exclusively around the eyeball may be sufficient to achieve therapeutic effects.

Visual imagery influences brain responses to visual stimulation in bilateral cortical blindness.

Mental imagery is a powerful mechanism that may facilitate visual perception as well as compensate for it. The role of V1 in mental imagery is still a matter of debate. Our goal here was to investigate whether visual imagery was still possible in case of bilateral V1 destruction behaviorally evidenced by total clinical blindness and if so, whether it might boost residual visual perception. In a factorial fMRI design, faces, scenes or scrambled images were presented while a rare patient with cortical blindness over the whole visual field due to bilateral V1-lesions (TN) was instructed to imagine either an angry person or a neutral object (tree). The results show that visual imagery of a person activates frontal, parietal and occipital brain regions similar to control subjects and hence suggest that V1 is not necessary for visual imagery. In addition, the combination of visual stimulation and visual imagery of socio-emotional stimuli triggers activation in superior parietal lobule (SPL) and ventromedial (vmPFC) and dorsolateral prefrontal cortex (DLPFC). Finally, activation during residual vision, visual imagery and their interaction overlapped in the SPL, arguing for a central role of feeling in V1-independent vision and imagery.