Eyes open and eyes closed as rest conditions: impact on brain activation patterns

The patterns of associated brain activations during eyes-open and eyes-closed states in complete darkness considerably differ in fMRI. An "interoceptive" state with the eyes closed is characterized by visual cortex activation, while an "exteroceptive" state with the eyes open is characterized by ocular motor system activity. The impact of the chosen rest condition (eyes open or eyes closed in complete darkness) on the pattern of brain activations during visual stimulation was evaluated in 14 healthy volunteers. During fixation or dim light room illumination, the activation of the visual cortex was larger with the eyes-open rest condition than with the eyes-closed rest condition; however, activation of the lateral geniculate nucleus was smaller. Activations that can be attributed to ocular motor structures, such as the prefrontal cortex, parietal and frontal eye fields, cerebellar vermis, the thalamus, and basal ganglia were larger with the eyes-closed rest condition than with the eyes-open rest condition. BOLD signal decreases of cortical areas that represent visual, somatosensory, auditory, and vestibular functions were seen in the comparison fixation of light emitting diode (LED) minus eyes closed. Thus, the choice of rest condition (either eyes closed or eyes open) is critical for stimulus-induced brain activation patterns. Activity of the ocular motor system as well as deactivation of sensory cortical areas may go undetected with eyes open as rest condition.     

Gaze control and foot kinematics during stair climbing: characteristics leading to fall risk in progressive supranuclear palsy

BACKGROUND AND PURPOSE: Does gaze control influence lower-extremity motor coordination in people with neurological deficits? The purpose of this study was to determine whether foot kinematics during stair climbing are influenced by gaze shifts prior to stair step initiation. SUBJECTS AND METHODS: Twelve subjects with gaze palsy (mild versus severe) secondary to progressive supranuclear palsy were evaluated during a stair-climbing task in a cross-sectional study of mechanisms influencing eye-foot coordination. Infrared oculography and electromagnetic tracking sensors measured eye and foot kinematics, respectively. The primary outcome measures were vertical gaze fixation scores, foot lift asymmetries, and sagittal-plane foot trajectories. RESULTS: The subjects with severe gaze palsy had significantly lower lag foot lift relative to lead foot lift than those with a mild form of gaze palsy. The lag foot trajectory for the subjects with severe gaze palsy tended to be low, with a heading toward contact with the edge of the stair. SUBJECTS:with severe gaze palsy were 28 times more likely to experience "fixation intrusion" (high vertical gaze fixation score) during an attempted shift of gaze downward than those with mild ocular motor deficits (odds ratio [OR]=28.3, 95% confidence interval [CI]=6.4-124.8). Subjects with severe gaze shift deficits also were 4 times more likely to have lower lag foot lift with respect to lead foot lift than those with mild ocular motor dysfunction (OR=4.0, 95% CI=1.7-9.7). DISCUSSION AND CONCLUSION: The small number of subjects and the variation in symptom profiles make the generalization of findings preliminary. Deficits in gaze control may influence stepping behaviors and increase the risk of trips or falls during stair climbing. Neural and kinematic hypotheses are discussed as possible contributing mechanisms.     

Asymmetrical activation of human visual cortex demonstrated by functional MRI with monocular stimulation

We have demonstrated asymmetric activation patterns in the visual cortices of normal humans who have undergone functional MRI with monocular photic stimulation. The contralateral hemisphere is activated more strongly and to a greater spatial extent than the ipsilateral hemisphere when either eye is stimulated. This asymmetry can be explained by nasotemporal asymmetries which have been described in anatomical studies of the visual system in primates and humans. In part, the representation of the monocular crescent of the temporal hemifield of either eye, which exists only in the crossed projection, may explain this. In addition, within the binocular field, there is a biased crossed projection of nasal retinal ganglion cells which drive the contralateral ocular dominance columns in V1. Finally, the blind spot representation in the ipsilateral visual cortex may also contribute to the observed asymmetries. Our study may in effect provide a functional correlate of the anatomical asymmetries that have been observed in humans and animals.     

Ocular motor measures in migraine with and without aura

The purpose of this study was to examine basic ocular motor function in individuals with migraine. We used an infrared eye-tracking system to measure horizontal smooth pursuit to a sinusoidal target, saccades to horizontal target displacements of 5-20 degrees , and the stability of fixation in 19 migraine without aura (MoA), 19 migraine with aura (MA) and 19 headache-free control (C) subjects. Eye movement measurements were made at two target displacement rates and against both homogeneous grey and patterned backgrounds. We found no statistically significant differences between migraine and control subjects in any of the eye movement parameters measured, but did find highly significant effects of both target speed and background pattern in all groups. Our results do not provide support for subclinical cerebellar impairment in migraineurs, and do provide evidence that previously described visual abnormalities in migraine are not artefacts of abnormal fixation or eye movements.     

fMRI signal decreases in ipsilateral primary motor cortex during unilateral hand movements are related to duration and side of movement

Interactions between the primary motor cortices of each hemisphere during unilateral hand movements appear to be inhibitory, although there is evidence that the strengths of these interactions are asymmetrical. In the present study, functional magnetic resonance imaging (fMRI) was used to investigate the effects of motor task duration and hand used on unilateral movement-related BOLD signal increases and decreases in the hand region of primary motor cortex (M1) of each hemisphere in six right-handed volunteers. Significant task-related BOLD signal decreases were observed in ipsilateral M1 during single and brief bursts of unilateral movements for both hands. However, these negative-to-baseline responses were found to intensify with increasing movement duration in parallel with greater task-related increases in contralateral M1. Movement-related BOLD signal decreases in ipsilateral M1 were also stronger for the right, dominant hand than for the left hand in our right-handed subjects. These findings would be consistent with the existence of interhemispheric interactions between M1 of each hemisphere, whereby increased neuronal activation in M1 of one hemisphere induces reduced neuronal activity in M1 of the opposite hemisphere. The observation of a hemispheric asymmetry in inhibition between M1 of each hemisphere agrees well with previous neuroimaging and electrophysiological data. These findings are discussed in the context of current understanding of the physiological origins of negative-to-baseline BOLD responses.     

A BOLD signature of eyeblinks in the visual cortex

We are usually unaware of the brief but large illumination changes caused by blinks, presumably because of blink suppression mechanisms. In fMRI however, increase of the BOLD signal was reported in the visual cortex, e.g. during blocks of voluntary blinks (Bristow, Frith and Rees, 2005) or after spontaneous blinks recorded during the prolonged fixation of a static stimulus (Tse, Baumgartner and Greenlee, 2010). We tested whether such activation, possibly related to illumination changes, was also present during standard fMRI retinotopic and visual experiments and was large enough to contaminate the BOLD signal we are interested in. We monitored in a 3T scanner the eyeblinks of 14 subjects who observed three different types of visual stimuli, including periodic rotating wedges and contracting/expanding rings, event-related Mondrians and graphemes, while fixating. We performed event-related analyses on the set of detected spontaneous blinks. We observed large and widespread BOLD responses related to blinks in the visual cortex of every subject and whatever the visual stimulus. The magnitude of the modulation was comparable to visual stimulation. However, blink-related activations lay mostly in the anterior parts of retinotopic visual areas, coding the periphery of the visual field well beyond the extent of our stimuli. Blinks therefore represent an important source of BOLD variations in the visual cortex and a troublesome source of noise since any correlation, even weak, between the distribution of blinks and a tested protocol could trigger artifactual activities. However, the typical signature of blinks along the anterior calcarine and the parieto-occipital sulcus allows identifying, even in the absence of eyetracking, fMRI protocols possibly contaminated by a heterogeneous distribution of blinks.     

Head position modulates activity in the human parietal eye fields

For us to interact with our environment we need to know where objects are around us, relative to our body. In monkeys, a body-centered map of visual space is known to exist within the parietal eye fields. This map is formed by the modulation of retinal responses by gain fields to gaze position. In humans, no map of body-centered space has yet been discovered but clinical data suggest that the right parietal lobe is predominantly responsible for visuospatial function. Using functional MRI, we have been able to demonstrate that an area in the intraparietal sulcus of humans has properties very similar to the parietal eye fields of monkeys. This area demonstrates BOLD signal changes related to the visual, saccadic, and memory components of saccade tasks that are analogous to the visual, saccadic, and memory responses of neurons within the parietal eye fields of monkeys. More importantly, the amount of signal change seen in this region is modulated by head position relative to the body, suggesting that a gain field dependent body-centered representation of space exists bilaterally within the parietal lobes in humans.     

Automatic attention orienting by social and symbolic cues activates different neural networks: an fMRI study

Visual attention can be automatically re-oriented by another person's non-predictive gaze as well as by symbolic arrow cues. We investigated whether the shifts of attention triggered by biologically relevant gaze cues and biologically non-relevant arrow cues rely on the same neural systems by comparing the effects of gaze-cued and arrow-cued orienting on blood oxygenation level-dependent (BOLD) signal in humans. Participants detected laterally presented reaction signals preceded by centrally presented non-predictive gaze and arrow cues. Directional gaze cues and arrow cues were presented in separate blocks. Furthermore, two separate control blocks were run in which non-directional cues (straight gaze or segment of a line) were used. The BOLD signals during the control blocks were subtracted from those during the respective blocks with directional cues. Behavioral data showed that, for both cue types, reaction times were shorter on congruent than incongruent trials. Imaging data revealed three foci of activation for gaze-cued orienting: in the left inferior occipital gyrus and right medial and inferior occipital gyri. For arrow-cued orienting, a much more extensive network was activated. There were large postcentral activations bilaterally including areas in the medial/inferior occipital gyri and medial temporal gyri and in the left intraparietal area. Interestingly, arrow cuing also activated the right frontal eye field and supplementary eye field. The results suggest that attention orienting by gaze cues and attention orienting by arrow cues are not supported by the same cortical network and that attention orienting by symbolic arrow cues relies on mechanisms associated with voluntary shifts of attention.     

Measurement of ocular aberrations in downward gaze using a modified clinical aberrometer

Changes in corneal optics have been measured after downward gaze. However, ocular aberrations during downward gaze have not been previously measured. A commercial Shack-Hartmann aberrometer (COAS-HD) was modified by adding a relay lens system and a rotatable beam splitter to allow on-axis aberration measurements in primary gaze and downward gaze with binocular fixation. Measurements with the modified aberrometer (COAS-HD relay system) in primary and downward gaze were validated against a conventional aberrometer. In human eyes, there were significant changes (p<0.05) in defocus C(2,0), primary astigmatism C(2,2) and vertical coma C(3,-1) in downward gaze (25 degrees) compared to primary gaze, indicating the potential influence of biomechanical forces on the optics of the eye in downward gaze. To demonstrate a further clinical application of this modified aberrometer, we measured ocular aberrations when wearing a progressive addition lens (PAL) in primary gaze (0 degree), 15 degrees downward gaze and 25 degrees downward gaze.     

Retinotopic maps and hemodynamic delays in the human visual cortex measured using arterial spin labeling

Cortical representations of the visual field are organized retinotopically, such that nearby neurons have receptive fields at nearby locations in the image. Many studies have used blood oxygenation level-dependent (BOLD) fMRI to non-invasively construct retinotopic maps in humans. The accuracy of the maps depends on the spatial extent of the metabolic and hemodynamic changes induced by the neural activity. Several studies using gradient-echo MRI at 1.5 T and 3 T showed that most of the BOLD signal originates from veins, which might lead to a spatial displacement from the actual site of neuronal activation, thus reducing the specificity of the functional localization. In contrast to BOLD signal, cerebral blood flow (CBF) as measured using arterial spin labeling (ASL) is less or not at all affected by remote draining veins, and therefore spatially and temporally more closely linked to the underlying neural activity. In the present study, we determined retinotopic maps in the human brain using CBF as well as using BOLD signal in order to compare their spatial relationship and the temporal delays of each imaging modality for visual areas V1, V2, V3, hV4 and V3AB. We tested the robustness and reproducibility of the maps across different sessions, calculated the overlap as well as signal delay times across visual areas. While area boundaries were relatively well preserved, we found systematic differences of response latencies between CBF and the BOLD signal between areas. In summary, CBF data obtained using ASL allows reliable retinotopic maps to be constructed; this approach is, therefore, suitable for studying visual areas especially in close proximity to large veins where the BOLD signal is spatially inaccurate.     

眼固视成分分离的研究现状及应用进展

背景：研究表明,固视期间的眼动,不仅包含了来自神经系统的噪声信号,而且包含认知加工的信息,固视成分及其功能的研究也日益引起重视。目的：综述固视成分分离的研究现状及进展。方法：分别以“visualfixation,fixationaleyemovement,tremor．drifts,microsaccades”为关键词,利用计算机检索1980至2012年PebMed数据库,并使用Google学术进行相关文献搜索,以及参考相应专著,排除内容重复、无关及缺乏原创性的文献,保留64篇文献做进一步分析。结果与结论：固视是个体的眼睛保持对准被观察物体的一种现象,伴随有微颤、漂移和微跳视3种眼动成分,它们是维持视知觉的重要条件。近年来,研究者针对固视3种成分对视知觉的贡献进行了探讨,主要包括防止知觉消退和对视觉系统进行纠错两种观点。目前,研究者通过对眼动速度阈限的估计来分离微跳视成分。未来的研究可以从固视眼动的神经生理基础以及神经活动的记录技术和视网膜固定技术的提高等方面展开,从而加深对固视眼动现象的理解。     

The cortical eye proprioceptive signal modulates neural activity in higher-order visual cortex as predicted by the variation in visual sensitivity

Whereas the links between eye movements and the shifts in visual attention are well established, less is known about how eye position affects the prioritization of visual space. It was recently observed that visual sensitivity varies with the direction of gaze and the level of excitability in the eye proprioceptive representation in human left somatosensory cortex (S1(EYE)), so that after 1Hz repetitive transcranial magnetic stimulation (rTMS) over S1(EYE), targets presented nearer the center of the orbit are detected more accurately. Here we used whole-brain functional magnetic resonance imaging to map areas where S1(EYE)-rTMS affects the neural response evoked by retinally identical stimuli depending on the direction of rotation of the right eye. After S1(EYE)-rTMS, a single area in the left cuneus outside Brodmann Areas 17/18 showed an increased neuronal response to a right hemifield target when the right eye was rotated leftwards as compared with when it was rotated rightwards. This effect was larger after S1(EYE)-rTMS than after rTMS of a control area in the motor cortex. The neural response to retinally identical stimuli in this area could be predicted from the changes in visual detectability observed previously, but not from the location of the visual targets relative to the body. These results strongly argue for a modulatory connection from the eye proprioceptive area in the somatosensory cortex to the higher-order visual cortex. This connection may contribute to flexibly allocate priorities for visual perception depending on the proprioceptively signaled direction of gaze.     

Effects of unilateral brain damage on contralateral and ipsilateral upper extremity function in hemiplegia

This article describes the long-term effects of unilateral penetrating hemispheric lesions on contralateral and ipsilateral upper extremity motor performance and functional outcome. Activities-of-daily-living skill and gross motor performance contralateral to the lesions were compared among 32 left-sided and 19 right-sided hemiplegic subjects using analysis of variance and chi-square techniques. Ipsilateral to the damaged hemisphere, fine motor tasks of simple visual motor reaction time, grip and pinch strength, finger tapping, and Purdue Pegboard performance were tested. Analysis of covariance compared each ipsilateral task to performance in the corresponding hand of 70 matched controls. Results indicate similar long-term functional ADL outcome in right and left hemisphere-damaged subjects, despite more severe contralateral functional motor deficits following lesions of the left hemisphere. Right hemisphere lesions led to ipsilateral decrements in reaction time, and lesions of either hemisphere diminished grip or pinch strength, finger tapping, and pegboard performance ipsilaterally. These results demonstrate that unilateral brain damage involving the motor areas of either hemisphere has detrimental effects on ipsilateral upper extremity motor function. Findings are discussed and related to the concept that the left hemisphere is specialized or has greater neuronal representation for bilateral motor processes. Physical therapists involved in the treatment of patients with hemiplegia should be aware that motor functions of the ipsilateral, nonparetic upper extremity may also be affected adversely by unilateral brain lesions.     

Popout modulates focal attention in the primary visual cortex

The influence of context-dependent interactions on attention-related neural activity was studied in the human primary visual cortex (V1) with event-related fMRI. Retinotopic field-sign mapping was used to determine the localization of V1 with respect to adjacent retinotopic areas. Observers reported the orientation of a Gabor patch at pre-cued extrafoveal locations when it was salient among distractor Gabors and when it was not. Saliency was caused by local orientation contrast between Gabors-a mechanism that is thought to arise from context-dependent interactions in the V1 proper. A comparison of the attention-related BOLD response for salient and non-salient stimuli in V1 revealed that salient Gabors caused a significantly smaller BOLD response than non-salient Gabors. This differential effect was not observed in higher-order visual areas (V3/V3A, MT+/LO, IPS). When attention was not focused onto the target, the size of the BOLD response was generally reduced in all visual areas, and no difference was seen in V1 for salient and non-salient Gabors. These findings suggest that contextual interactions underlying saliency influence attentional modulations in V1 and support the view that perceptual and attentional mechanisms share neural circuits at this early stage of visual processing.     

Subthreshold high-frequency TMS of human primary motor cortex modulates interconnected frontal motor areas as detected by interleaved fMRI-TMS

To elucidate changes in human brain activity evoked by repetitive transcranial magnetic stimulation (rTMS), sub- and suprathreshold rTMS (4 Hz, 10 s) over the left primary sensorimotor cortex (M1/S1) was interleaved with blood-oxygenation-level-dependent (BOLD) echo-planar imaging of primary and secondary motor areas. Suprathreshold rTMS over left M1/S1 caused marked increases in BOLD signal in the stimulated area and SMA-proper in seven of eight subjects. By contrast, we found no change in BOLD signal in the stimulated M1/S1, when rTMS was given at intensities that were subthreshold for inducing motor responses in the contralateral hand. However, five of eight subjects showed consistent increases in BOLD MRI signal in the SMA-proper and, to a lesser extent, in bilateral lateral premotor cortex (LPMC) during subthreshold rTMS. A decrease in BOLD MRI signal was found in contralateral (right) M1/S1 in 6/8 subjects across all conditions. No significant changes were observed in the pre-SMA. The results support the notion that BOLD MRI responses to suprathreshold rTMS over M1/S1 are dominated by neuronal activity related to reafferent processing of TMS-induced hand movements. At subthreshold intensity, a short train of high-frequency rTMS seems to predominantly modulate activity of corticocortical connections which link the stimulated area with remote frontal premotor areas.     

Where left becomes right: a magnetoencephalographic study of sensorimotor transformation for antisaccades

To perform a saccadic response to a visual stimulus, a 'sensorimotor transformation' is required (i.e., transforming stimulus location into a motor command). Where in the brain is this accomplished? While previous monkey neurophysiology and human fMRI studies examined either parietal cortex or frontal eye field, we studied both of these regions simultaneously using magnetoencephalography (MEG). Nineteen healthy participants performed a pseudorandom series of prosaccades and antisaccades during MEG. Antisaccades require a saccade in the direction opposite a suddenly appearing stimulus. We exploited this dissociation between stimulus and saccadic direction to identify cortical regions that show early activity for a contralateral stimulus and late activity for a contralateral saccade. We found that in the left hemisphere both the intraparietal sulcus and the frontal eye field showed a pattern of activity consistent with sensorimotor transformation - a transition from activity reflecting the direction of the stimulus to that representing the saccadic goal. These findings suggest that sensorimotor transformation is the product of coordinated activity across the intraparietal sulcus and frontal eye field, key components of a cortical network for saccadic generation.     

Parametric reverse correlation reveals spatial linearity of retinotopic human V1 BOLD response

Many experiments measuring blood oxygen level dependent (BOLD) signal in functional magnetic resonance imaging (fMRI) data assume that the BOLD signal is predominantly linear in space and time. Previous investigations of temporal linearity have reported that the temporal BOLD response contains both linear and nonlinear components. Here, we used a novel method to investigate spatial linearity of BOLD within area V1. The visual field was divided into regions shaped like wedges, rings, or the intersections of the wedges and rings. The appearance of a flickering checkerboard texture within each region was governed by an independent M-sequence. fMRI data were acquired as the human subjects maintained visual fixation on a central cross. The time series data from each voxel were cross-correlated with every stimulus sequence to estimate each voxel's BOLD responses to all independent regions of the visual field. Linearity by spatial summation was assessed directly by comparing responses to wedges and rings with sums of responses to component patches. The BOLD responses of voxels responding positively to stimuli, measured with independent stimuli subtending several degrees of visual angle, were well predicted by linear spatial summation.     

Ocular motor abnormalities in Wallenberg's lateral medullary syndrome.

The ocular motor abnormalities that commonly occur in Wallenberg's lateral medullary syndrome are often unappreciated. These abnormalities include signs of dysfunction of ocular alignment (skew deviation, ocular tilt reaction, and environmental tilt), various types of nystagmus, smooth pursuit and gaze-holding abnormalities (eye deviation, ipsipulsion or lateropulsion, and impaired contralateral pursuit), and saccadic abnormalities (ipsipulsion and torsipulsion). These impairments of ocular motor control and their proposed mechanisms are discussed.     

Central luminance flicker can activate peripheral retinotopic representation

We aimed to study cortical responses to uniform luminance stimulus in different conditions. We stimulated the central visual field with luminance flicker and reversal of checkerboard pattern contrast and mapped the visual field representation up to 50 degrees of eccentricity. Our results show spreading of cortical BOLD responses when visual stimulus contains mean luminance change in dark surround and no spreading when the stimulus surround has bright illumination. No cortical region was more sensitive to luminance flicker than to pattern reversal during both stimulation setups. We suggest that the spread of luminance responses in retinotopic cortical areas results from intraocular scattering of light. Light scattered inside the eye spreads visual stimulation on the retina, and the contrast of the scattered light is strongest when the surround of the stimulus is dark. The stray light is potential and often neglected source of an artefact in visual experiments, and the responses due to stray light can erroneously be interpreted as indicators for local cortical sensitivity to luminance.     

Role of hyperactive cerebellum and motor cortex in Parkinson's disease

Previous neuroimaging studies have found hyperactivation in the cerebellum and motor cortex and hypoactivation in the basal ganglia in patients with Parkinson's disease (PD) but the relationship between the two has not been established. This study examined whether cerebellar and motor cortex hyperactivation is a compensatory mechanism for hypoactivation in the basal ganglia or is a pathophysiological response that is related to the signs of the disease. Using a BOLD contrast fMRI paradigm PD patients and healthy controls performed automatic and cognitively controlled thumb pressing movements. Regions of interest analysis quantified the BOLD activation in motor areas, and correlations between the hyperactive and hypoactive regions were performed, along with correlations between the severity of upper limb rigidity and BOLD activation. There were three main findings. First, the putamen, supplementary motor area (SMA) and pre-SMA were hypoactive in PD patients. The left and right cerebellum and the contralateral motor cortex were hyperactive in PD patients. Second, PD patients had a significant negative correlation between the BOLD activation in the ipsilateral cerebellum and the contralateral putamen. The correlation between the putamen and motor cortex was not significant. Third, the BOLD activation in the motor cortex was positively correlated with the severity of upper limb rigidity, but the BOLD activation in the cerebellum was not correlated with rigidity. Further, the activation in the motor cortex was not correlated with upper extremity bradykinesia. These findings provide new evidence supporting the hypothesis that hyperactivation in the ipsilateral cerebellum is a compensatory mechanism for the defective basal ganglia. Our findings also provide the first evidence from neuroimaging that hyperactivation in the contralateral primary motor cortex is not a compensatory response but is directly related to upper limb rigidity.