Tactile stimulation partially prevents neurodevelopmental changes in visual tract caused by early iron deficiency.

Iron deficiency has a critical impact on maturational mechanisms of the brain and the damage related to neuroanatomical parameters is not satisfactorily reversed after iron replacement. However, emerging evidence suggest that enriched early experience may offer great therapeutic efficacy in cases of nutritional disorders postnatally, since the brain is remarkably responsive to its interaction with the environment. Given the fact that tactile stimulation (TS) treatment has been previously shown to be an effective therapeutic approach and with potential application to humans, here we ask whether exposure to TS treatment, from postnatal day (P) 1 to P32 for 3min/day, could also be employed to prevent neuroanatomical changes in the optic nerve of rats maintained on an iron-deficient diet during brain development. We found that iron deficiency changed astrocyte, oligodendrocyte, damaged fiber, and myelinated fiber density, however, TS reversed the iron-deficiency-induced alteration in oligodendrocyte, damaged fiber and myelinated fiber density, but failed to reverse astrocyte density. Our results suggest that early iron deficiency may act by disrupting the timing of key steps in visual system development thereby modifying the normal progression of optic nerve maturation. However, optic nerve development is sensitive to enriching experiences, and in the current study we show that this sensitivity can be used to prevent damage from postnatal iron deficiency during the critical period.

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.

A Predominantly Visual Subdivision of The Right Temporo-Parietal Junction (vTPJ).

A multiplicity of sensory and cognitive functions has been attributed to the large cortical region at the temporo-parietal junction (TPJ). Using functional MRI, we report that a small region lateralized within the right TPJ responds robustly to certain simple visual stimuli ("vTPJ"). The vTPJ was found in all right hemispheres (n = 7), posterior to the auditory cortex. To manipulate stimuli and attention, subjects were presented with a mixture of visual and auditory stimuli in a concurrent block design in 2 experiments: (1) A simple visual stimulus (a grating pattern modulating in mean luminance) elicited robust responses in the vTPJ, whether or not the subject attended to vision and(2) a drifting low-contrast dartboard pattern of constant mean luminance evoked robust responses in the vTPJ when it was task-relevant (visual task), and smaller responses when it was not (auditory task). The results suggest a focal, visually responsive region within the right TPJ that is powerfully driven by certain visual stimuli (luminance fluctuations), and that can be driven by other visual stimuli when the subject is attending. The precise localization of this visually responsive region is helpful in segmenting the TPJ and to better understand its role in visual awareness and related disorders such as extinction and neglect.

Natural scenes viewing alters the dynamics of functional connectivity in the human brain.

Spontaneous fMRI fluctuations are organized in large-scale spatiotemporal structures, or resting-state networks (RSN). However, it is unknown how task performance affects RSN dynamics. We use MEG to measure slow (∼0.1 Hz) coherent fluctuations of band-limited power (BLP), a robust correlate of RSN, during rest and movie observation and compare them to fMRI-RSN. BLP correlation, especially in α band, dropped in multiple RSN during movie although overall topography was maintained. Variability of power correlation increased in visual occipital cortex, and transient decrements corresponded to scenes perceived as "event boundaries." Additionally, stronger task-dependent interactions developed between vision and language networks in θ and ß bands, and default and language networks in γ band. The topography of fMRI connectivity and relative changes induced by the movie were well matched to MEG. We conclude that resting-state and task network interactions are clearly different in the frequency domain despite maintenance of underlying network topography.

Vasomotion and neurovascular coupling in the visual thalamus in vivo.

Spontaneous contraction and relaxation of arteries (and in some instances venules) has been termed vasomotion and has been observed in an extensive variety of tissues and species. However, its functions and underlying mechanisms are still under discussion. We demonstrate that in vivo spectrophotometry, measured simultaneously with extracellular recordings at the same locations in the visual thalamus of the cat, reveals vasomotion, measured as an oscillation (0.14 hz) in the recorded oxyhemoglobin (OxyHb) signal, which appears spontaneously in the microcirculation and can last for periods of hours. During some non-oscillatory periods, maintained sensory stimulation evokes vasomotion lasting ~30s, resembling an adaptive vascular phenomenon. This oscillation in the oxyhaemoblobin signal is sensitive to pharmacological manipulation: it is inducible by chloralose anaesthesia and it can be temporarily blocked by systemic administration of adrenaline or acetylcholine (ACh). During these oscillatory periods, neurovascular coupling (i.e. the relationship between local neural activity and the rate of blood supply to that location) appears significantly altered. This raises important questions with regard to the interpretation of results from studies currently dependent upon a linear relationship between neural activity and blood flow, such as neuroimaging.

Diminished top-down control underlies a visual imagery deficit in normal aging.

Mental imagery is involved in a wide variety of cognitive abilities, including reasoning, spatial navigation, and memory. Cognitive aging is associated with impairments in these abilities, suggesting that diminished fidelity of mental images in older adults may be related to diverse cognitive deficits. However, an age-related deficit in mental imagery and its role in memory impairment is still a matter of debate. Previous human fMRI studies demonstrated that visual imagery activates representations in category-selective visual cortex via top-down control mechanisms. Here, we use fMRI to show that normal aging is associated with diminished selectivity of visual cortex activation during visual imagery, with a corresponding reduction in the selectivity of functional connections between prefrontal cortex and visual cortices. Moreover, a relationship between reduced imagery selectivity and visual memory in older adults was established. These results reveal that aging disrupts neural networks that subserve mental imagery and offers evidence of this as a factor in age-related memory decline.

Gypenoside attenuates white matter lesions induced by chronic cerebral hypoperfusion in rats.

Cerebral white matter lesions (WMLs) are frequently observed in vascular dementia and Alzheimer's disease and are believed to be responsible for cognitive dysfunction. The cerebral WMLs are most likely caused by chronic cerebral hypoperfusion and can be experimentally induced by permanent bilateral common carotid artery occlusion (BCCAO) in rats. Previous studies found the involvement of oxidative stress and astrocytic activation in the cerebral WMLs of BCCAO rats. Gypenoside (GP), a pure component extracted from the Gyrostemma pentaphyllum Makino, a widely reputed medicinal plants in China, has been reported to have some neuroprotective effects via anti-oxidative stress and anti-inflammatory mechanisms. In the present study, we investigated the protective effect of GP against cerebral WMLs and the underlying mechanisms for its inhibition of cognitive decline in BCCAO rats. Adult male Sprague-Dawley rats were orally administered daily doses of 200 and 400mg/kg GP for 33 days after BCCAO, and spatial learning and memory were assessed using the Morris water maze. Following behavioral testing, oxygen free radical levels and antioxidative capability were measured biochemically. The levels of lipid peroxidation and oxidative DNA damage were also assessed by immunohistochemical staining for 4-hydroxynonenal and 8-hydroxy-2'-deoxyguanosine, respectively. Activated astrocytes were also assessed by immunohistochemical staining and Western blotting with GFAP antibodies. The morphological changes were stained with Klüver-Barrera. Rats receiving 400mg/kg GP per day performed significantly better in tests for spatial learning and memory than saline-treated rats. GP 400mg/kg per day were found to markedly scavenge oxygen free radicals, enhance antioxidant abilities, decrease lipid peroxide production and oxidative DNA damage, and inhibit the astrocytic activation in corpus callosum and optic tract in BCCAO rats. However, GP 200mg/kg per day had no significant effects. GP may have therapeutic potential for treating dementia induced by chronic cerebral hypoperfusion and further evaluation is warranted.

The effects of electrical microstimulation on cortical signal propagation.

Electrical stimulation has been used in animals and humans to study potential causal links between neural activity and specific cognitive functions. Recently, it has found increasing use in electrotherapy and neural prostheses. However, the manner in which electrical stimulation-elicited signals propagate in brain tissues remains unclear. We used combined electrostimulation, neurophysiology, microinjection and functional magnetic resonance imaging (fMRI) to study the cortical activity patterns elicited during stimulation of cortical afferents in monkeys. We found that stimulation of a site in the lateral geniculate nucleus (LGN) increased the fMRI signal in the regions of primary visual cortex (V1) that received input from that site, but suppressed it in the retinotopically matched regions of extrastriate cortex. Consistent with previous observations, intracranial recordings indicated that a short excitatory response occurring immediately after a stimulation pulse was followed by a long-lasting inhibition. Following microinjections of GABA antagonists in V1, LGN stimulation induced positive fMRI signals in all of the cortical areas. Taken together, our findings suggest that electrical stimulation disrupts cortico-cortical signal propagation by silencing the output of any neocortical area whose afferents are electrically stimulated.

Seeing faces and objects with the "mind's eye".

With the advent of functional brain imaging techniques and recent developments in the analysis of cortical connectivity, the focus of mental imagery studies has shifted from a semi-modular approach to a more realistic, integrated, cortical networks perspective. Recent studies of visual imagery of faces and objects suggest that activation of content-specific representations stored in the ventral visual stream is top-down modulated by parietal and frontal regions. The relation of these findings to other cognitive functions is discussed, as well as their clinical implications for patients with impaired states of conscious awareness.

Combined functional MRI and diffusion tensor imaging analysis of visual motion pathways.

BACKGROUND: Motion perception may be preserved after damage to striate cortex (primary visual cortex, area V1). Awareness and normal discrimination of fast-moving stimuli have been observed even in the complete absence of V1. These facts suggest that motion-sensitive cortex (the V5/MT complex or V5/MT+) may be activated by direct thalamic or collicular inputs that bypass V1. Such projections have been identified previously in monkeys but have not been shown in humans using neuroimaging techniques. METHODS: We used diffusion tensor imaging (DTI) tractography to visualize white matter fiber tracts connecting with V5/MT+ in 10 healthy volunteers. V5/MT+ was localized for each subject using functional MRI (fMRI). Functional activity maps were overlaid on high-resolution anatomical images and registered with the diffusion-weighted images to define V5/MT+ as the region of interest (ROI) for DTI tractography analysis. Fibers connecting to V1 were excluded from the analysis. RESULTS: Using conservative tractography parameters, we found connections between the V5/MT+ region and the posterior thalamus and/or superior colliculus in 4 of 10 subjects. CONCLUSIONS: Connections between the V5/MT+ region and the posterior thalamus and/or superior colliculus may explain visual motion awareness in the absence of a functioning V1.

Comparison of visual cortical activations induced by electro-acupuncture at vision and nonvision-related acupoints.

In the current study, we investigated whether or not stimulation at vision and nonvision-related acupoints was able to induce similarity in the time domain, although stimulation at different acupoints could produce similar spatial distributions. This phenomenon still remains uncertain and contradictory. We introduced a novel experimental paradigm using a modified non-repeated event-related (NRER) design, and utilized the methods of independent component analysis (ICA) combined with seed correlated functional connectivity analysis to locate visual cortical activations and to study their temporal characteristics during electro-acupuncture (EAS) at vision-related acupoint GB 37 and nonvision-related acupoint KI 8. Results showed that strong activations were present in the visual cortical areas (BA 17/18/19) at both acupoints, but temporal correlation analysis indicated that they were modulated in opposite directions during the resting state after acupuncture. Our results revealed that acupuncture at vision and nonvision-related acupoints can induce similar activations in spatial distribution but different modulation effects temporally.

Spatial attention can modulate audiovisual integration at multiple cortical and subcortical sites.

The role of attention in multisensory integration (MI) is presently uncertain, with some studies supporting an automatic, pre-attentive process and others suggesting possible modulation through selective attention. The goal of this functional magnetic resonance imaging study was to investigate the role of spatial attention on the processing of congruent audiovisual speech stimuli (here indexing MI). Subjects were presented with two simultaneous visual streams (speaking lips in the left and right visual hemifields) plus a single central audio stream (spoken words). In the selective attention conditions, the auditory stream was congruent with one of the two visual streams. Subjects attended to either the congruent or the incongruent visual stream, allowing the comparison of brain activity for attended vs. unattended MI while the amount of multisensory information in the environment and the overall attentional requirements were held constant. Meridian mapping and a lateralized 'speaking-lips' localizer were used to identify early visual areas and to localize regions responding to contralateral visual stimulations. Results showed that attention to the congruent audiovisual stimulus resulted in increased activation in the superior temporal sulcus, striate and extrastriate retinotopic visual cortex, and superior colliculus. These findings demonstrate that audiovisual integration and spatial attention jointly interact to influence activity in an extensive network of brain areas, including associative regions, early sensory-specific visual cortex and subcortical structures that together contribute to the perception of a fused audiovisual percept.

Effects of visual and auditory feedback on sensorimotor circuits in the basal ganglia.

Previous work using visual feedback has identified two distinct sensorimotor circuits in the basal ganglia (BG): one that scaled with the duration of force and one that scaled with the rate of change of force. The present study compared functional MRI signal changes in the BG during a grip force task using either visual or auditory feedback to determine whether the BG nuclei process auditory and visual feedback similarly. We confirmed the same two sensorimotor circuits in the BG. Activation in the striatum and external globus pallidus (GPe) scaled linearly with the duration of force under visual and auditory feedback conditions, with similar slopes and intercepts across feedback type. The pattern of signal change for the internal globus pallidus (GPi) and subthalamic nucleus (STN) was nonlinear and parameters of the exponential function were altered by feedback type. Specifically, GPi and STN activation decreased exponentially with the rate of change of force. The rate constant and asymptote of the exponential functions for GPi and STN were greater during auditory than visual feedback. In a comparison of the BOLD signal between BG regions, GPe had the highest percentage of variance accounted for and this effect was preserved for both feedback types. These new findings suggest that neuronal activity of specific BG nuclei is affected by whether the feedback is derived from visual or auditory inputs. Also, the data are consistent with the hypothesis that the GPe has a high level of information convergence from other BG nuclei, which is preserved across different sensory feedback modalities.

Voice familiarity engages auditory cortex.

Familiarity with a speaker's voice has been shown to enhance its auditory processing, implicating physiological effects at the level of the auditory cortex, although auditory cortical involvement has not previously been demonstrated. Eleven healthy right-handed male participants performed two tasks during blood oxygenation level-dependent functional MRI at 1.5 T. Both tasks used the same vocal stimuli. In task 1, they classified speakers as familiar or unfamiliar. In task 2, they judged stimuli as being in the right or left auditory field. Our analysis showed an area of auditory cortex on the lower bank of the superior temporal sulcus that was preferentially activated by familiar voices in both tasks. Familiar voices may elicit access to detailed sensory expectations, allowing enhanced auditory cortical processing.

Aggressive behavior and posterior cerebral artery stroke.

OBJECTIVE: To describe the mechanisms leading to aggressive behavior among patients with acute posterior cerebral artery stroke. DESIGN, SETTING, AND PATIENTS: We prospectively included all of the patients with posterior cerebral artery stroke and aggressive behavior admitted to our department from January 1, 2003, to December 31, 2004. Patients with history of stroke, cognitive impairment, or prior history of psychiatric disease were excluded. RESULTS: Aggressive behavior was found in 3 patients (7.3%) among 41 patients with posterior cerebral artery stroke. One patient had right occipitotemporal and ventrolateral thalamic stroke. The second patient had left occipitotemporal and lateral thalamic stroke. The third patient had right isolated occipital stroke. In addition to a contralateral homonymous hemianopsia, the patients, who were physically and emotionally balanced before the stroke, suddenly manifested an acute, unusual, aggressive behavior. The patients became agitated and aggressive when they were stimulated by the environment, and they responded to solicitation by their relatives or medical personnel by shouting obscenities and hitting and biting others. In all of the 3 cases, temporary physical restraint was required and neuroleptics were administered. This unusual behavioral pattern resolved within 2 weeks after stroke. CONCLUSIONS: Aggressive behavior is a rare presentation of acute posterior cerebral artery stroke, which may be difficult to diagnose in patients presenting with hemianopsia as the only concomitant neurological sign. The postulated mechanisms include dysfunction of the limbic or serotoninergic system.

Retinotopic effects during spatial audio-visual integration.

The successful integration of visual and auditory stimuli requires information about whether visual and auditory signals originate from corresponding places in the external world. Here we report crossmodal effects of spatially congruent and incongruent audio-visual (AV) stimulation. Visual and auditory stimuli were presented from one of four horizontal locations in external space. Seven healthy human subjects had to assess the spatial fit of a visual stimulus (i.e. a gray-scaled picture of a cartoon dog) and a simultaneously presented auditory stimulus (i.e. a barking sound). Functional magnetic resonance imaging (fMRI) revealed two distinct networks of cortical regions that processed preferentially either spatially congruent or spatially incongruent AV stimuli. Whereas earlier visual areas responded preferentially to incongruent AV stimulation, higher visual areas of the temporal and parietal cortex (left inferior temporal gyrus [ITG], right posterior superior temporal gyrus/sulcus [pSTG/STS], left intra-parietal sulcus [IPS]) and frontal regions (left pre-central gyrus [PreCG], left dorsolateral pre-frontal cortex [DLPFC]) responded preferentially to congruent AV stimulation. A position-resolved analysis revealed three robust cortical representations for each of the four visual stimulus locations in retinotopic visual regions corresponding to the representation of the horizontal meridian in area V1 and at the dorsal and ventral borders between areas V2 and V3. While these regions of interest (ROIs) did not show any significant effect of spatial congruency, we found subregions within ROIs in the right hemisphere that showed an incongruency effect (i.e. an increased fMRI signal during spatially incongruent compared to congruent AV stimulation). We interpret this finding as a correlate of spatially distributed recurrent feedback during mismatch processing: whenever a spatial mismatch is detected in multisensory regions (such as the IPS), processing resources are re-directed to low-level visual areas.

Deafferentation-disconnection neglect induced by posterior cerebral artery infarction.

OBJECTIVE: To investigate patients with posterior cerebral artery (PCA) infarctions to learn whether hemispatial neglect is more frequent and severe after right than left PCA infarction; whether visual field defects (VFDs) influence the presence or severity of hemispatial neglect; and the anatomic loci of lesions that are associated with hemispatial neglect. METHODS: The authors recruited 45 patients with PCA infarction that involved only the occipital lobe or the occipital lobe plus other areas served by the PCA. All subjects received seven neglect tests within 2 months after onset. RESULTS: Overall, the frequency of hemispatial neglect was 42.2%. The frequency did not significantly differ between the right (48.0%) and left (35.0%) PCA groups, but the severity of hemispatial neglect was significantly greater in the right group. VFD alone did not influence the frequency or severity of neglect after controlling other variables. Isolated occipital lesions were rarely associated with hemispatial neglect, and it was only the occipital plus splenial lesion that significantly influenced the frequency and severity of neglect. CONCLUSIONS: This study suggests that after excluding such confounding factors as aphasia or hemiplegia, neglect frequency does not differ between the right and left posterior cerebral artery (PCA) groups, but the severity of neglect is greater after right PCA infarctions; even in the acute stage of PCA infarction; visual field defect from an isolated occipital lesion does not cause hemispatial neglect; and the injury to both the occipital lobe and the splenium of the corpus callosum is important for producing hemispatial neglect with PCA infarction.

Retinotopic organization of visual mental images as revealed by functional magnetic resonance imaging.

In this study, we used event-related functional magnetic resonance imaging to investigate whether visual mental images retinotopically activate early visual cortex. Six participants were instructed to visualize or view horizontally or vertically oriented flashing bow-tie shaped stimuli. When compared to baseline, imagery globally activated Area V1. When the activation evoked by the stimuli at the different orientations was directly compared, distinct spatial activation patterns were obtained for each orientation in most participants. Not only was the topography of the activation patterns from imagery similar to the topography obtained with a corresponding visual perception task, but it closely matched the individual cortical representation of either the horizontal or the vertical visual field meridians. These findings strongly support that visual imagery and perception share low-level anatomical substrate and functional processes. Binding of spatial features is suggested as one possible mechanism.