Enhanced excitability of the human visual cortex induced by short-term light deprivation

Long-term deprivation of visual input for several days or weeks leads to marked changes in the excitability and function of the occipital cortex. The time course of these changes is poorly understood. In this study, we addressed the question whether a short period of light deprivation (minutes to a few hours) can elicit such changes in humans. Noninvasive transcranial magnetic stimulation (TMS) of the human occipital cortex can evoke the perception of flashes or spots of light (phosphenes). To assess changes in visual cortex excitability following light deprivation, we measured the minimum intensity of stimulation required to elicit phosphenes (phosphene threshold) and the number of phosphenes elicited by different TMS stimulus intensities (stimulus-response curves). A reduced phosphene threshold was detected 45 min after the onset of light deprivation and persisted for the entire deprivation period (180 min). Following re-exposure to light, phosphene thresholds returned to predeprivation values over 120 min. Stimulus-response curves were significantly enhanced in association with this intervention. In a second experiment, we studied the effects of light deprivation on functional magnetic resonance imaging (fMRI) signals elicited by photic stimulation. fMRI results showed increased visual cortex activation after 60 min of light deprivation that persisted following 30 min of re-exposure to light. Our results demonstrated a substantial increase in visual cortex excitability. These changes may underlie behavioral gains reported in humans and animals associated with light deprivation.     

Monocular visual deprivation suppresses excitability in adult human visual cortex

The adult visual cortex maintains a substantial potential for plasticity in response to a change in visual input. For instance, transcranial magnetic stimulation (TMS) studies have shown that binocular deprivation (BD) increases the cortical excitability for inducing phosphenes with TMS. Here, we employed TMS to trace plastic changes in adult visual cortex before, during, and after 48 h of monocular deprivation (MD) of the right dominant eye. In healthy adult volunteers, MD-induced changes in visual cortex excitability were probed with paired-pulse TMS applied to the left and right occipital cortex. Stimulus-response curves were constructed by recording the intensity of the reported phosphenes evoked in the contralateral visual field at range of TMS intensities. Phosphene measurements revealed that MD produced a rapid and robust decrease in cortical excitability relative to a control condition without MD. The cortical excitability returned to preinterventional baseline levels within 3 h after the end of MD. The results show that in contrast to the excitability increase in response to BD, MD acutely triggers a reversible decrease in visual cortical excitability. This shows that the pattern of visual deprivation has a substantial impact on experience-dependent plasticity of the human visual cortex.     

The interaction of brain regions during visual search processing as revealed by transcranial magnetic stimulation

Although it has long been known that right posterior parietal cortex (PPC) has a role in certain visual search tasks, and human motion area V5 is involved in processing tasks requiring attention to motion, little is known about how these areas may interact during the processing of a task requiring the speciality of each. Using transcranial magnetic stimulation (TMS), this study first established the specialization of each area in the form of a double dissociation; TMS to right PPC disrupted processing of a color/form conjunction and TMS to V5 disrupted processing of a motion/form conjunction. The key finding of this study is, however, if TMS is used to disrupt processing of V5 at its critical time of activation during the motion/form conjunction task, concurrent disruption of right PPC now has a significant effect, where TMS at PPC alone does not. Our findings challenge the conventional interpretation of the role of right PPC in conjunction search and spatial attention.     

Contributions of the PPC to online control of visually guided reaching movements assessed with fMRI-guided TMS

The posterior parietal cortex (PPC) plays an important role in controlling voluntary movements by continuously integrating sensory information about body state and the environment. We tested which subregions of the PPC contribute to the processing of target- and body-related visual information while reaching for an object, using a reaching paradigm with 2 types of visual perturbation: displacement of the visual target and displacement of the visual feedback about the hand position. Initially, functional magnetic resonance imaging (fMRI) was used to localize putative target areas involved in online corrections of movements in response to perturbations. The causal contribution of these areas to online correction was tested in subsequent neuronavigated transcranial magnetic stimulation (TMS) experiments. Robust TMS effects occurred at distinct anatomical sites along the anterior intraparietal sulcus (aIPS) and the anterior part of the supramarginal gyrus for both perturbations. TMS over neighboring sites did not affect online control. Our results support the hypothesis that the aIPS is more generally involved in visually guided control of movements, independent of body effectors and nature of the visual information. Furthermore, they suggest that the human network of PPC subregions controlling goal-directed visuomotor processes extends more inferiorly than previously thought. Our results also point toward a good spatial specificity of the TMS effects.     

Spontaneous fluctuations in posterior alpha-band EEG activity reflect variability in excitability of human visual areas

Neural activity fluctuates dynamically with time, and these changes have been reported to be of behavioral significance, despite occurring spontaneously. Through electroencephalography (EEG), fluctuations in alpha-band (8-14 Hz) activity have been identified over posterior sites that covary on a trial-by-trial basis with whether an upcoming visual stimulus will be detected or not. These fluctuations are thought to index the momentary state of visual cortex excitability. Here, we tested this hypothesis by directly exciting human visual cortex via transcranial magnetic stimulation (TMS) to induce illusory visual percepts (phosphenes) in blindfolded participants, while simultaneously recording EEG. We found that identical TMS-stimuli evoked a percept (P-yes) or not (P-no) depending on prestimulus alpha-activity. Low prestimulus alpha-band power resulted in TMS reliably inducing phosphenes (P-yes trials), whereas high prestimulus alpha-values led the same TMS-stimuli failing to evoke a visual percept (P-no trials). Additional analyses indicated that the perceptually relevant fluctuations in alpha-activity/visual cortex excitability were spatially specific and occurred on a subsecond time scale in a recurrent pattern. Our data directly link momentary levels of posterior alpha-band activity to distinct states of visual cortex excitability, and suggest that their spontaneous fluctuation constitutes a visual operation mode that is activated automatically even without retinal input.     

Priming of motion direction and area V5/MT: a test of perceptual memory

Presentation of supraliminal or subliminal visual stimuli that can (or cannot) be detected or identified can improve the probability of the same stimulus being detected over a subsequent period of seconds, hours or longer. The locus and nature of this perceptual priming effect was examined, using suprathreshold stimuli, in subjects who received repetitive pulse transcranial magnetic stimulation over the posterior occipital cortex, the extrastriate motion area V5/MT or the right posterior parietal cortex during the intertrial interval of a visual motion direction discrimination task. Perceptual priming observed in a control condition was abolished when area V5/MT was stimulated but was not affected by magnetic stimulation over striate or parietal sites. The effect of transcranial magnetic stimulation (TMS) on priming was specific to site (V5/MT) and to task - colour priming was unaffected by TMS over V5/MT. The results parallel, in the motion domain, recent demonstrations of the importance of macaque areas V4 and TEO for priming in the colour and form domains.     

Right parietal cortex plays a critical role in change blindness

There is increasing evidence from functional magnetic resonance imaging (fMRI) that visual awareness is not only associated with activity in ventral visual cortex but also with activity in the parietal cortex. However, due to the correlational nature of neuroimaging, it remains unclear whether this parietal activity plays a causal role in awareness. In the experiment presented here we disrupted activity in right or left parietal cortex by applying repetitive transcranial magnetic stimulation (rTMS) over these areas while subjects attempted to detect changes between two images separated by a brief interval (i.e. 1-shot change detection task). We found that rTMS applied over right parietal cortex but not left parietal cortex resulted in longer latencies to detect changes and a greater rate of change blindness compared with no TMS. These results suggest that the right parietal cortex plays a critical role in conscious change detection.     

Distinct causal influences of parietal versus frontal areas on human visual cortex: evidence from concurrent TMS-fMRI

It has often been proposed that regions of the human parietal and/or frontal lobe may modulate activity in visual cortex, for example, during selective attention or saccade preparation. However, direct evidence for such causal claims is largely missing in human studies, and it remains unclear to what degree the putative roles of parietal and frontal regions in modulating visual cortex may differ. Here we used transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) concurrently, to show that stimulating right human intraparietal sulcus (IPS, at a site previously implicated in attention) elicits a pattern of activity changes in visual cortex that strongly depends on current visual context. Increased intensity of IPS TMS affected the blood oxygen level-dependent (BOLD) signal in V5/MT+ only when moving stimuli were present to drive this visual region, whereas TMS-elicited BOLD signal changes were observed in areas V1-V4 only during the absence of visual input. These influences of IPS TMS upon remote visual cortex differed significantly from corresponding effects of frontal (eye field) TMS, in terms of how they related to current visual input and their spatial topography for retinotopic areas V1-V4. Our results show directly that parietal and frontal regions can indeed have distinct patterns of causal influence upon functional activity in human visual cortex.     

Parieto-frontal interactions in visual-object and visual-spatial working memory: evidence from transcranial magnetic stimulation.

This study aimed to investigate whether transcranial magnetic stimulation (TMS) can induce selective working memory (WM) deficits of visual-object versus visual-spatial information in normal humans. Thirty-five healthy subjects performed two computerized visual n-back tasks, in which they were required to memorize spatial locations or abstract patterns. In a first series of experiments, unilateral or bilateral TMS was delivered on posterior parietal and middle temporal regions of both hemispheres after various delays during the WM task. Bilateral temporal TMS increased reaction times (RTs) in the visual-object, whereas bilateral parietal TMS selectively increased RTs in the visual-spatial WM task. These effects were evident at a delay of 300 ms. Response accuracy was not affected by bilateral or unilateral TMS of either cortical region. In a second group of experiments, bilateral TMS was applied over the superior frontal gyrus (SFG) or the dorsolateral prefrontal cortex (DLPFC). TMS of the SFG selectively increased RTs in the visual-spatial WM task, whereas TMS of the DLPFC interfered with both WM tasks, in terms of both accuracy and RTs. These effects were evident when TMS was applied after a delay of 600 ms, but not one of 300 ms. These findings confirm the segregation of WM buffers for object and spatial information in the posterior cortical regions. In the frontal cortex, the DLPFC appears to be necessary for WM computations regardless of the stimulus material.     

Introducing navigated transcranial magnetic stimulation as a refined brain mapping methodology

A major intrinsic limitation of transcranial magnetic stimulation (TMS) to map the human brain lies in the unclear relationship between the position of the stimulating coil on the scalp and the underlying stimulated cortex. The relationship between structure and function as the major feature constituting a brain mapping modality can therefore not be established. Recent advances in image processing allowed us to refine TMS by combining magnetic resonance imaging (MRI) modalities with TMS using a neuronavigation system to measure the position of the stimulating coil and map this position onto a MRI data set. This technique has several advantages over recent TMS mapping strategies. The position of the coil on the scalp can be held constant as verified by real time visual guidance. When evaluating higher cortical functions, the relationship between underlying cortical anatomy and the scalp stimulation site can be accurately assessed. Cortical motor output maps can be easily obtained for preoperative planning and decision making for mass lesions near rolandic cortex in patients. In conclusion, navigated TMS is a reliable alternative for localizing cortical functions and therefore may be a useful adjunct or in selected patients even a helpful alternative to other functional neuroimaging methods. Electronic Publication     

Introducing navigated transcranial magnetic stimulation as a refined brain mapping methodology.

A major intrinsic limitation of transcranial magnetic stimulation (TMS) to map the human brain lies in the unclear relationship between the position of the stimulating coil on the scalp and the underlying stimulated cortex. The relationship between structure and function as the major feature constituting a brain mapping modality can therefore not be established. Recent advances in image processing allowed us to refine TMS by combining magnetic resonance imaging (MRI) modalities with TMS using a neuronavigation system to measure the position of the stimulating coil and map this position onto a MRI data set. This technique has several advantages over recent TMS mapping strategies. The position of the coil on the scalp can be held constant as verified by real time visual guidance. When evaluating higher cortical functions, the relationship between underlying cortical anatomy and the scalp stimulation site can be accurately assessed. Cortical motor output maps can be easily obtained for preoperative planning and decision making for mass lesions near rolandic cortex in patients. In conclusion, navigated TMS is a reliable alternative for localizing cortical functions and therefore may be a useful adjunct or in selected patients even a helpful alternative to other functional neuroimaging methods.     

Abnormal changes of synaptic excitability in migraine with aura

Migraine patients are characterized by altered cortical excitability and information processing between attacks. The relationship between these abnormalities is still poorly understood. In this study, visual evoked potentials (VEP) and proton magnetic resonance spectroscopy were recorded simultaneously in migraineurs and healthy subjects. In order to investigate the homeostatic-like plasticity in the visual cortex, cortical excitability was modified using transcranial direct current stimulation (tDCS). Before any stimulation, migraineurs showed significantly higher glutamate/creatine ratios (Glx/Cr) than healthy subjects. In healthy subjects, excitatory (anodal) tDCS caused an increase and inhibitory (cathodal) tDCS a decrease in the Glx/Cr ratio. Subsequent photic stimulation (PS) reversed the changes in Glx/Cr ratios, which returned back to baseline, demonstrating homeostatic-like metaplasticity in the control group. In migraine patients, both anodal and cathodal tDCS decreased the Glx/Cr ratio, which did not return to baseline after PS. While healthy subjects showed an increase in VEP amplitude under anodal and a reduction under cathodal tDCS, the modifiability of VEP under tDCS was reduced in migraineurs. The results demonstrate a reduced responsiveness of the occipital cortex to interventions that change cortical excitability in migraine. Moreover, altered glutamatergic neurotransmission seems to mediate the relation between abnormal cortical information processing and excitability in migraineurs.     

Circadian modulation of GABA-mediated cortical inhibition

Circadian rhythms exert powerful influence on various aspects of human physiology and behavior. Here, we tested changes of human cerebral cortex excitability over the course of the day with transcranial magnetic stimulation (TMS). At different times of the day, intracortical and corticospinal excitability of the primary motor cortex (M1) was evaluated in 15 healthy subjects by TMS of left M1. While motor thresholds, short-interval intracortical inhibition and facilitation and input/output curves remained unchanged, we found that a specific form of γ-aminobutyric acid (GABA)-mediated intracortical inhibition, revealed by long-interval intracortical inhibition and cortical silent periods, progressively decreased during the course of the day. Additional experiments demonstrated that morning inhibition persisted irrespective of previous sleep or sleep deprivation. Corticotropin-releasing hormone (CRH) infusions in the evening lead to morning cortisol levels but did not restore levels of morning inhibition, whereas suppression of endogenous CRH release by repeated oral dexamethasone intake over 24 h prevented morning inhibition. The findings suggest a specific modulation of GABAergic motor cortex inhibition within the circadian cycle, possibly linked to the CRH system, and may indicate a neurobiological basis for variable neuroplasticity over the course of the day.     

Cortical connections of functional zones in posterior parietal cortex and frontal cortex motor regions in new world monkeys

We examined the connections of posterior parietal cortex (PPC) with motor/premotor cortex (M1/PM) and other cortical areas. Electrical stimulation (500 ms trains) delivered to microelectrode sites evoked movements of reach, defense, and grasp, from distinct zones in M1/PM and PPC, in squirrel and owl monkeys. Tracer injections into M1/PM reach, defense, and grasp zones showed dense connections with M1/PM hand/forelimb representations. The densest inputs outside of frontal cortex were from PPC zones. M1 zones were additionally connected with somatosensory hand/forelimb representations in areas 3a, 3b, and 1 and the somatosensory areas of the upper bank of the lateral sulcus (S2/PV). Injections into PPC zones showed primarily local connections and the densest inputs outside of PPC originated from M1/PM zones. The PPC reach zone also received dense inputs from cortex caudal to PPC, which likely relayed visual information. In contrast, the PPC grasp zone was densely connected with the hand/forelimb representations of areas 3a, 3b, 1, and S2/PV. Thus, the dorsal parietal-frontal network involved in reaching was preferentially connected to visual cortex, whereas the more ventral network involved in grasping received somatosensory inputs. Additional weak interlinks between dissimilar zones (e.g., PPC reach and PPC grasp) were apparent and may coordinate actions.     

Theta-burst stimulation over human frontal cortex distorts perceptual stability across eye movements

We perceive a stable outside world despite the constant changes of visual input induced by our eye movements. Internal monitoring of a corollary discharge associated with oculomotor commands may help to anticipate the perceptual consequences of impending eye movements. The primate frontal eye fields have repeatedly been presumed to participate in the maintenance of perceptual stability across eye movements. However, a direct link between integrity of frontal oculomotor areas and perceptual stability is missing so far. Here, we show that transcranial magnetic stimulation (TMS) over the right human frontal cortex impairs the integration of visual space across eye movements. We asked 9 healthy subjects to report the direction of transsaccadic stimulus displacements and applied TMS before the actual experiment in a novel offline stimulation protocol, continuous theta-burst stimulation (cTBS). A systematic perceptual distortion was observed after stimulation over the right frontal cortex that was best explained by an internal underestimation of executed eye movement amplitudes. cTBS apparently disturbed an internal prediction process for contraversive saccades, while the metrics of associated oculomotor actions remained unchanged. Our findings suggest an important role of the frontal cortex in the internal monitoring of oculomotor actions for the perceptual integration of space across eye movements.     

Study of tactile perception based on phosphene positioning using simulated prosthetic vision

Abstract:  In recent years, as stimulation electrodes have been implanted in the visual cortex, optic nerve, and retina to generate visual perceptions (phosphenes), the research on prosthetic vision has become a popular topic. After implantation, it is crucial to evaluate the characteristics of the stimulated phosphenes. Until now, several methods using tactile perception are proposed to describe the phosphene position, but no systematic study of the perceptional behavior has been performed. Here, an experimental study of tactile perception based on phosphene positioning was proposed using simulated prosthetic vision. Results show that the dispersion was smaller and the response time was less when phosphenes are generated in near visual field compared to the far visual field. The dispersion, the accuracy, and the response speed were better when using the visual guide. Moreover, the widely used method of using the left hand as reference and the right hand to point the phosphene may cause geographic error.     

Search for color 'center(s)' in macaque visual cortex

It is often stated that color is selectively processed in cortical area V4, in both macaques and humans. However most recent data suggests that color is instead processed in region(s) antero-ventral to V4. Here we tested these two hypotheses in macaque visual cortex, where 'V4' was originally defined, and first described as color selective. Activity produced by equiluminant color-varying (versus luminance-varying) gratings was measured using double-label deoxyglucose in awake fixating macaques, in multiple areas of flattened visual cortex. Much of cortex was activated near-equally by both color- and luminance-varying stimuli. In remaining cortical regions, discrete color-biased columns were found in many cortical visual areas, whereas luminance-biased activity was found in only a few specific regions (V1 layer 4B and area MT). Consistent with a recent hypothesis, V4 was not uniquely specialized for color processing, but areas located antero-ventral to V4 (in/near TEO and anterior TE) showed more color-biased activity.     

Dorsal premotor cortex exerts state-dependent causal influences on activity in contralateral primary motor and dorsal premotor cortex

During voluntary action, dorsal premotor cortex (PMd) may exert influences on motor regions in both hemispheres, but such interregional interactions are not well understood. We used transcranial magnetic stimulation (TMS) concurrently with event-related functional magnetic resonance imaging to study such interactions directly. We tested whether causal influences from left PMd upon contralateral (right) motor areas depend on the current state of the motor system, involving regions engaged in a current task. We applied short bursts (360 ms) of high- or low-intensity TMS to left PMd during single isometric left-hand grips or during rest. TMS to left PMd affected activity in contralateral right PMd and primary motor cortex (M1) in a state-dependent manner. During active left-hand grip, high (vs. low)-intensity TMS led to activity increases in contralateral right PMd and M1, whereas activity decreases there due to TMS were observed during no-grip rest. Analyses of condition-dependent functional coupling confirmed topographically specific stronger coupling between left PMd and right PMd (and right M1), when high-intensity TMS was applied to left PMd during left-hand grip. We conclude that left PMd can exert state-dependent interhemispheric influences on contralateral cortical motor areas relevant for a current motor task.     

Dorsal posterior parietal rTMS affects voluntary orienting of visuospatial attention

Patients with lesions in posterior parietal cortex (PPC) are relatively unimpaired in voluntarily directing visual attention to different spatial locations, while many neuroimaging studies in healthy subjects suggest dorsal PPC involvement in this function. We used an offline repetitive transcranial magnetic stimulation (rTMS) protocol to study this issue further. Ten healthy participants performed a cue-target paradigm. Cues prompted covert orienting of spatial attention under voluntary control to either a left or right visual field position. Targets were flashed subsequently at the cued or uncued location, or bilaterally. Following rTMS over right dorsal PPC, (i) the benefit for target detection at cued versus uncued positions was preserved irrespective of cueing direction (left- or rightward), but (ii) leftward cueing was associated with a global impairment in target detection, at all target locations. This reveals that leftward orienting was still possible after right dorsal PPC stimulation, albeit at an increased overall cost for target detection. In addition, rTMS (iii) impaired left, but (iv) enhanced right target detection after rightward cueing. The finding of a global drop in target detection during leftward orienting with a spared, relative detection benefit at the cued (left) location (i-ii) suggests that right dorsal PPC plays a subsidiary rather than pivotal role in voluntary spatial orienting. This finding reconciles seemingly conflicting results from patients and neuroimaging studies. The finding of attentional inhibition and enhancement occurring contra- and ipsilaterally to the stimulation site (iii-iv) supports the view that spatial attention bias can be selectively modulated through rTMS, which has proven useful to transiently reduce visual hemispatial neglect.     

Stages of motor output reorganization after hemispheric stroke suggested by longitudinal studies of cortical physiology

Reorganization of motor circuits in the cerebral cortex is thought to contribute to recovery following stroke. These can be examined with transcranial magnetic stimulation (TMS) using measures of corticospinal tract integrity and intracortical excitability. However, little is known about how these changes develop during the important early period post-stroke and their influence on recovery. We used TMS to obtain multiple measures bilaterally in a group of 10 patients during the early days and weeks and up to 6 months post-stroke, in order to examine correlations with tests of hand function. Ten age-matched healthy subjects were also studied. After stroke, day-to-day variation in performance was unrelated to physiological measures in the first 3 weeks. Measures of corticospinal integrity averaged over the same period correlated well with hand function, but this relationship became weaker at 3 months. In contrast, most intracortical excitability measures did not correlate acutely but did so strongly at 3 months. Thus in the acute stage, patients' performance is limited by damage to corticospinal output. Improved performance at 3 months may depend on reorganization in alternative cortical networks to maximize the efficiency of remaining corticospinal pathways--intracortical disinhibition may aid recovery by promoting access to these networks.