Different trajectories of decline for global form and global motion processing in aging, mild cognitive impairment and Alzheimer's disease.

The visual processing of complex motion is impaired in Alzheimer's disease (AD). However, it is unclear whether these impairments are biased toward the motion stream or part of a general disruption of global visual processing, given some reports of impaired static form processing in AD. Here, for the first time, we directly compared the relative preservation of motion and form systems in AD, mild cognitive impairment, and healthy aging, by measuring coherence thresholds for well-established global rotational motion and static form stimuli known to be of equivalent complexity. Our data confirm a marked motion-processing deficit specific to some AD patients, and greater than any form-processing deficit for this group. In parallel, we identified a more gradual decline in static form recognition, with thresholds raised in mild cognitive impairment patients and slightly further in the AD group compared with controls. We conclude that complex motion processing is more vulnerable to decline in dementia than complex form processing, perhaps owing to greater reliance on long-range neural connections heavily targeted by AD pathology.

Dissociations in Coherence Sensitivity Reveal Atypical Development of Cortical Visual Processing in Congenital Achromatopsia.

PURPOSE: While basic visual functions have been described in subjects with congenital achromatopsia (ACHM), little is known about their mid- or high-level cortical visual processing. We compared midlevel cortical visual processing in ACHM subjects (n = 11) and controls (n = 20). METHODS: Abilities to detect global form, global motion, and biological motion embedded in noise were tested across a range of light levels, including scotopic, in which both ACHM subjects and controls must rely on rods. Contrast sensitivity functions (CSFs) were also measured. RESULTS: Achromatopsia subjects showed differential impairments across tests. In scotopic conditions, global form was most impaired, while biological motion was normal. In a subset of three ACHM subjects with normal scotopic CSFs, two of the three showed global form perception worse than controls; all showed global motion comparable to controls; and strikingly, two of the three showed biological motion perception superior to controls. CONCLUSIONS: The cone signal appears to play a crucial role in the development of perception of global form, as in ACHM this is impaired even in scotopic conditions, in which controls also have to rely on rods, and even in ACHM subjects with no scotopic spatial vision loss. In contrast, the rod signal appears sufficient for the development of normal (or even superior) extrastriate biological motion perception. These results suggest that ACHM leads to atypical development of cortical vision, highlighting the need to better understand the potential for further reorganization of cortical visual processing following new therapies aimed at restoring cone function.

Cortical processing of global form, motion and biological motion under low light levels.

Advances in potential treatments for rod and cone dystrophies have increased the need to understand the contributions of rods and cones to higher-level cortical vision. We measured form, motion and biological motion coherence thresholds and EEG steady-state visual evoked potentials (SSVEP) responses under light conditions ranging from photopic to scotopic. Low light increased thresholds for all three kinds of stimuli; however, global form thresholds were relatively more impaired than those for global motion or biological motion. SSVEP responses to coherent global form and motion were reduced in low light, and motion responses showed a shift in topography from the midline to more lateral locations. Contrast sensitivity measures confirmed that basic visual processing was also affected by low light. However, comparison with contrast sensitivity function (CSF) reductions achieved by optical blur indicated that these were insufficient to explain the pattern of results, although the temporal properties of the rod system may also play a role. Overall, mid-level processing in extra-striate areas is differentially affected by light level, in ways that cannot be explained in terms of low-level spatiotemporal sensitivity. A topographical shift in scotopic motion SSVEP responses may reflect either changes to inhibitory feedback mechanisms between V1 and extra-striate regions or a reduction of input to the visual cortex. These results provide insight into how higher-level cortical vision is normally organised in absence of cone input, and provide a basis for comparison with patients with cone dystrophies, before and after treatments aiming to restore cone function.

The effect of blur on cortical responses to global form and motion.

Global form and motion sensitivity undergo long development in childhood with motion sensitivity rather than form being impaired in a number of childhood disorders and both impaired in adult clinical populations. This suggests extended development and vulnerability of extrastriate cortical areas associated with global processing. However, in some developmental and clinical populations, it remains unclear to what extent impairments might reflect deficits at earlier stages of visual processing, such as reduced visual acuity and contrast sensitivity. To address this, we investigated the impact of degraded spatial vision on cortical global form and motion processing in healthy adults. Loss of high spatial frequencies was simulated using a diffuser to blur the stimuli. Participants completed behavioral and EEG tests of global form and motion perception under three levels of blur. For the behavioral tests, participants' form and motion coherence thresholds were measured using a two-alternative, forced-choice procedure. Steady-state visual evoked potentials were used to measure cortical responses to changes in the coherence of global form and motion stimuli. Both global form and global motion perception were impaired with increasing blur as measured by elevated behavioral thresholds and reduced cortical responses. However, form thresholds showed greater impairment in both behavioral and EEG measures than motion thresholds at the highest levels of blur. The results suggest that high spatial frequencies play an important role in the perception of both global form and motion but are especially significant for global form. Overall, the results reveal complex interactions between low-level factors and global visual processing, highlighting the importance of taking these factors into account when investigating extrastriate function in low vision populations.

Improved Visual Perception in Very Low Birth Weight Infants on Enhanced Nutrient Supply.

BACKGROUND: Optimal nutrient supply to very low birth weight (VLBW: BW <1,500 g) infants is important for growth and neurodevelopment. Growth restriction is common among these infants and may be associated with neurocognitive impairments. OBJECTIVES: To compare an enhanced nutrient supply to a routine supply given to VLBW infants and to evaluate the effects on visual perception of global form and motion measured by visual event-related potentials (VERP). METHODS: A total of 50 VLBW infants were randomized to an intervention group that received an increased supply of energy, protein, fat, essential fatty acids, and vitamin A or a control group that received standard nutritional care. At 5 months' corrected age the infants were examined using VERP to investigate the responses to global form and motion. VERP were analysed at the first (f1) and third (f3) harmonics of the stimulus frequency. RESULTS: Data from 31 subjects were eligible for analysis. The motion VERP responses for the f1 and f3 components were stronger in the area near the posterior midline region in the intervention group compared to the controls in the group analyses (p = 0.02 and p = 0.001, respectively). CONCLUSION: The results showed a more consistent response to global motion among infants receiving enhanced nutrition. The intervention may have improved visual perception of global motion.

Development of visual motion processing: phase and peak latencies of direction-specific visual evoked potential.

The direction-reversal visual evoked potential (DR-VEP) latency is a key measure of the development of motion processing in infancy. However, the latency of this response has not been previously investigated. For other stimuli, both the latency of an initial peak and a latency measure calculated from steady-state phase as a function of frequency have been shown to be important and distinctive indicators of development. The latter measure is hypothesized to reflect the time course of cortical processing beyond the initial response that generates the first positive peak. DR-VEP was tested in 61 adults at 1-16 reversals per second (r/s) and 76 infants (age 7.7-79.0 weeks) at 2-8 r/s. In addition to measuring the transient peak latency at 1-3 r/s, latencies from the gradient of phase against reversal rates were also calculated from steady-state recordings at 1-16 r/s. For both adults and infants, peak latencies were similar for 1-3 r/s, while the calculated latency was substantially longer. Thirty-nine percent of adults and 17% of infants showed additional early transient peaks. We suggest that this early peak may reflect activation of extrastriate areas by motion, by a route that bypasses V1. While both transient latencies were similar to adult values around the onset of DR responses at 10 weeks of age, the latency calculated from phase values did not asymptote to the adult value of 207 ms until around 30 weeks. The overall time course of the response to direction reversal is prolonged compared with the transmission delay that generates the initial transient peak, presumably reflecting feed-forward, lateral, and recurrent connections that refine and elaborate the directional response of cortical neurons. While the peak latencies stay relatively unchanged throughout development, the dynamics of further motion processing are not mature until after 8 months of age. These measures may prove important indicators of motion development in future clinical evaluations.

Orientation-reversal VEP: comparison of phase and peak latencies in adults and infants.

The peak latency of pattern-reversal (PR)-VEP has been found to develop rapidly, reaching the adult level around 15 weeks of age. However, the development of orientation-reversal (OR)-VEP, reflecting the specific spatial organization of cortical receptive fields, still remains unknown. OR-VEP was tested in 81 adults at 1-12 reversals/sec (r/s) and 94 infants (age 4-79 weeks) at 2-8r/s. OR data at 4r/s from an additional 123 infants (age 4.0-20.3 weeks) studied previously were also analyzed. In addition to peak transient latencies at 1-4r/s, latency values derived from the gradient of phase against temporal frequency in steady-state recording were also calculated. For both adults and infants, no significant latency differences in the initial positive peaks were found among the low reversal rates. The calculated latency was statistically longer than the transient latency in both groups. While the transient latency asymptoted to adult value of 102 ms at around 50 weeks of age, the calculated latency, unlike that for PR-VEP, showed little variation across the age span. The data suggest a dominant effect of transmission delay on the initial peak in infancy, which reduces with age. However, the overall timing of the cortical response to orientation change remains slower than for pattern reversal in the fully developed visual cortex. Upon reaching maturity, the latencies of the initial positive peak in both pattern and orientation VEPs may arise from the same level of cortical processing in V1, but the overall time course reflected in the steady-state phase continues to show a much more prolonged response to orientation change than the transmission delay seen in the transient VEPs.

Latency measures of pattern-reversal VEP in adults and infants: different information from transient P1 response and steady-state phase.

PURPOSE: Temporal properties such as the peak latency of pattern-reversal (PR) visual evoked potentials (VEPs) have been found to be a sensitive indicator of visual development. Latency can be assessed from the slope of a plot of phase against temporal frequency (TF) for steady state VEP measurements as well as from the transient P1 peak. This study aimed to discover whether the two methods provide different information regarding early visual development. METHODS: Developmental changes of the transient peak latency were tracked using low TFs of one to four reversals per second (r/s) and a spatial frequency (SF) of 0.24 cycles per degree (cpd) in comparison with latencies calculated from the phase versus TF gradient in the range of 1 to 19 r/s. PR-VEP responses were recorded from 81 adults and 137 infants (ages 3.6-79 weeks). RESULTS: Values of the calculated and transient peak latencies were similar in adults, but the calculated latency was statistically longer than transient peak latency in younger infants. Moreover, while the transient peak latency asymptoted to an adult value of 104 ms at approximately 15 weeks of age, the calculated latency did not asymptote until after 30 weeks. CONCLUSIONS: In this study, the effectiveness of the phase-based method to calculate latency was confirmed. In infants, the rapid decrease of P1 latency may be due to the progressive maturation of conduction time in the afferent visual pathways, with the development of adult levels of phase-based calculated latency being due to the maturation of later cortical processing in infants.

VERP and brain imaging for identifying levels of visual dorsal and ventral stream function in typical and preterm infants.

Visual development is a key area for understanding and assessing early brain development. Different levels in the hierarchy of visual processing, from the initial response to flashes of light, through selective responses to contour orientation and motion in primary visual cortex (V1), to global processing in extrastriate of large-scale patterns of form and motion, can each be assessed using stimuli designed to isolate specific neural activity in visual event-related potentials (VERPs). This approach has been used to reveal the sequence of emergence of different visual cortical functions in the first 6 months of typical human development, and to provide early indicators of anomalies in brain development. Delayed or absent onset of orientation-reversal (OR-)VERPs, as a measure of cortical development, has been shown to be a sensitive indicator of perinatal brain damage in both term-born and prematurely born infants. Direction-reversal (DR-)VERPs appear a few weeks later than OR-VERPs in typical development, and are further delayed in even healthy children born preterm, reflecting possible early vulnerability of the motion (dorsal stream) system. High-density recordings of responses to global motion and global form patterns show that these extrastriate systems are typically functional by 5 months of age, but the topography of the activity distributions shows that the brain systems underlying these responses are radically reorganized between infancy and adulthood. In prematurely born infants whose structural brain MRI was evaluated at birth, the onset of the response is absent or delayed in those with severe brain injury, while in those with mild/moderate brain injury the response is present but its spatial organization is further from the adult pattern than those in controls. These findings are related to the development of distinct networks of brain areas in the dorsal and ventral cortical streams, and the apparent vulnerability of the dorsal-stream network in a wide range of both genetic and acquired developmental disorders.

Basic visual function and cortical thickness patterns in posterior cortical atrophy.

Posterior cortical atrophy (PCA) is characterized by a progressive decline in higher-visual object and space processing, but the extent to which these deficits are underpinned by basic visual impairments is unknown. This study aimed to assess basic and higher-order visual deficits in 21 PCA patients. Basic visual skills including form detection and discrimination, color discrimination, motion coherence, and point localization were measured, and associations and dissociations between specific basic visual functions and measures of higher-order object and space perception were identified. All participants showed impairment in at least one aspect of basic visual processing. However, a number of dissociations between basic visual skills indicated a heterogeneous pattern of visual impairment among the PCA patients. Furthermore, basic visual impairments were associated with particular higher-order object and space perception deficits, but not with nonvisual parietal tasks, suggesting the specific involvement of visual networks in PCA. Cortical thickness analysis revealed trends toward lower cortical thickness in occipitotemporal (ventral) and occipitoparietal (dorsal) regions in patients with visuoperceptual and visuospatial deficits, respectively. However, there was also a lot of overlap in their patterns of cortical thinning. These findings suggest that different presentations of PCA represent points in a continuum of phenotypical variation.

Differential human brain activation by vertical and horizontal global visual textures.

Mid-level visual processes which integrate local orientation information for the detection of global structure can be investigated using global form stimuli of varying complexity. Several lines of evidence suggest that the identification of concentric and parallel organisations relies on different underlying neural substrates. The current study measured brain activation by concentric, horizontal parallel, and vertical parallel arrays of short line segments, compared to arrays of randomly oriented segments. Six subjects were scanned in a blocked design functional magnetic resonance imaging experiment. We compared percentage BOLD signal change during the concentric, horizontal and vertical blocks within early retinotopic areas, the fusiform face area and the lateral occipital complex. Unexpectedly, we found that vertical and horizontal parallel forms differentially activated visual cortical areas beyond V1, but in general, activations to concentric and parallel forms did not differ. Vertical patterns produced the highest percentage signal change overall and only area V3A showed a significant difference between concentric and parallel (horizontal) stimuli, with the former better activating this area. These data suggest that the difference in brain activation to vertical and horizontal forms arises at intermediate or global levels of visual representation since the differential activity was found in mid-level retinotopic areas V2 and V3 but not in V1. This may explain why earlier studies--using methods that emphasised responses to local orientation--did not discover this vertical-horizontal anisotropy.

Reorganization of global form and motion processing during human visual development.

The functional selectivity of human primary visual cortex (V1) for orientation and motion direction is established by around 3 months of age [1-3], but there have been few studies of the development of extrastriate visual areas that integrate outputs from V1 [4-8]. We investigated sensitivity and topographical organization for global form and motion with high-density visual event-related potentials (VERPs) in 4- to 5-month-old infants and adults. Responses were measured to transitions between concentrically organized elements (short arc segments for form, dot trajectories for motion) and random arrangements. Adults showed topographically separate responses, with midline motion and more lateral form responses. Of 26 infants, 25 showed significant motion responses but only 13 showed form responses, suggesting more advanced development for extrastriate motion areas than form. Infants' form and motion responses were topographically distinct but contrasted with the corresponding adult topographies, with infants' motion responses more lateral than form responses. These results imply distinct neural sources at both ages and raise the possibility of substantial reorganization of extrastriate networks between infancy and adulthood. We speculate that global motion responses arise from area V5 in infants but are dominated by more medial areas such as V3/V3A and V6 in adults.

Asymmetrical cortical processing of radial expansion/contraction in infants and adults.

We report asymmetrical cortical responses (steady-state visual evoked potentials) to radial expansion and contraction in human infants and adults. Forty-four infants (22 3-month-olds and 22 4-month-olds) and nine adults viewed dynamic dot patterns which cyclically (2.1 Hz) alternate between radial expansion (or contraction) and random directional motion. The first harmonic (F1) response in the steady-state VEP response must arise from mechanisms sensitive to the global radial motion structure. We compared F1 amplitudes between expansion-random and contraction-random motion alternations. F1 amplitudes for contraction were significantly larger than those for expansion for the older infants and adults but not for the younger infants. These results suggest that the human cortical motion mechanisms have asymmetrical sensitivity for radial expansion vs. contraction, which develops at around 4 months of age. The relation between development of sensitivity to radial motion and cortical motion mechanisms is discussed.

Stereo and motion Dmax in infants.

These experiments compared the maximum displacement and disparity limits (Dmax) for apparent motion and stereopsis in random-dot displays in adult and 12-28 week-old infant subjects. Both stereo and motion Dmax increased during development, from about 0.3 deg in the youngest infants to 2 deg in adults. Some of the younger infants (12-14 weeks) did not give a stereo threshold, probably because stereopsis had not yet developed; but otherwise, the values of Dmax in the two domains were close to each other throughout the age range. These results suggest that both stereo and motion Dmax are limited by some common factor. Possible factors include receptive field sizes and internal noise. Simulations in which these were varied showed that while changes in both could contribute to the development of Dmax, only an increase in receptive field size can fully account for the rise in Dmax with age.

Orientation and motion-specific visual cortex responses in infants born preterm.

Orientation-specific cortical responses develop earlier in infancy than motion-specific responses. The maturation of orientation-reversal and direction-reversal visual evoked potentials was evaluated in 17 healthy, low risk, preterm infants (born <32 weeks gestation), compared with a group of 26 infants born at term. Both groups were studied at a corrected age of 2-4 months. The age function and magnitude of the orientation-reversal responses was similar in the two groups. Direction-reversal responses across the age range, however, were smaller in the preterm infants, suggesting a delayed maturation of motion processing. Reasons for the vulnerability of motion processing are discussed; the results may reflect anomalies of white matter development in preterm infants that are undetected by ultrasonography.

Interaction of spatial and temporal integration in global form processing.

The mechanisms by which global structure is extracted from local orientation information are not well understood. Sensitivity to global structure can be investigated using coherence thresholds for detection of global forms of varying complexity, such as parallel and concentric arrays of oriented line elements. In this study, we investigated temporal integration in the detection of these forms and its interaction with spatial integration. We find that for concentric patterns, integration times drop as region size increases from 3 degrees to 10.9 degrees , while for parallel patterns, the reverse is true. The same spatiotemporal relationship was found for Glass patterns as for line element arrays. The two types of organization therefore show quite different spatiotemporal relations, supporting previous arguments that different types of neural mechanism underlie their detection.

Dorsal-stream motion processing deficits persist into adulthood in Williams syndrome.

Previous studies of children with Williams syndrome (WS) have found a specific deficit in dorsal cortical stream function, indicated by poor performance in coherence thresholds for motion compared to form. Here we investigated whether this is a transient developmental feature or a persisting aspect of cerebral organization in WS. Motion and form coherence thresholds were tested in a group of 45 WS individuals aged 16-42 years, and 19 normal adult controls. Although there was considerable variation in the coherence thresholds across individuals with WS, the WS group showed overall worse performance than controls. A significant group x threshold condition interaction showed a substantially greater performance deficit for motion than for form coherence in the WS group relative to controls. This result suggests that the motion deficit is an enduring feature in WS and is a marker for one aspect of dorsal-stream vulnerability.

Motion- and orientation-specific cortical responses in infancy.

During the first 3 months, infants develop visual evoked potential (VEP) responses that are signatures of cortical orientation-selectivity and directional motion selectivity. Orientation-specific cortical responses develop in early infancy. This study compared these responses directly in the same infants, to investigate whether the later appearance of direction selectivity was intrinsic, or a function of the spatio-temporal characteristics of the stimuli used. Steady-state orientation-reversal (OR-) VEPs and direction-reversal (DR-) VEPs were recorded in infants aged 4-18 weeks. DR-VEPs were elicited with random pixel patterns and with gratings spatially similar to those used for OR-VEPs, at velocities of 5.5 and 11 deg/s, and reversal rates of 2 and 4 reversals/s. Infants throughout the age range showed significant responses to orientation-reversal. Direction-reversal responses appeared in less than 25% of infants under 7 weeks of age, rising to 80% or more at 11-13 weeks, whether tested with dots or gratings and for both speeds and reversal rates. However, 2 reversals/s elicits the DR-VEP on average about 2 weeks earlier than 4 reversal/s stimulation. We conclude that human cortical direction selectivity develops separately from orientation-selectivity and emerges at a later age, even with tests that are designed to optimise the former.

Normal and anomalous development of visual motion processing: motion coherence and 'dorsal-stream vulnerability'.

Directional motion processing is a pervasive and functionally important feature of the visual system. Behavioural and VEP studies indicate that it appears as a cortical function after about 7 weeks of age, with global processing, motion based segmentation, and the use of motion in complex perceptual tasks emerging shortly afterwards. A distinct, subcortical motion system controls optokinetic nystagmus (OKN) from birth, showing characteristic monocular asymmetries which disappear as binocular cortical function takes over in normal development. Asymmetries in cortical responses are linked to this interaction in a way that is not yet fully understood. Beyond infancy, a range of developmental disorders show a deficit of global motion compared to global form processing which we argue reflects a general 'dorsal-stream vulnerability'.

Motion processing asymmetries and stereopsis in infants.

These experiments used forced-choice preferential looking to test infants for preferences between pairs of random-dot patterns that moved in opposite directions. With monocularly-viewed horizontally moving patterns, 6-12-week-old infants showed a preference for nasalwards motion. With binocularly-viewed vertical motion, there was no overall preference, but the results did show a significant correlation between upwards bias of OKN and preference for downwards motion. In a longitudinal experiment, the nasalwards preference first appeared at 7-8 weeks, and thereafter persisted until the end of testing (23-25 weeks). In this experiment the infants were also tested for stereopsis, under conditions that were as nearly as possible identical to the direction preference test. There was no evidence that the onset of stereopsis had any effect on the directional asymmetry. The directional asymmetries revealed by these experiments appear to be distinct from the asymmetries of OKN and motion VEPs. It is possible that they reflect asymmetrical directional responses in extrastriate visual cortex (e.g. area V5/MT).