Validation of High-Resolution Tractography Against In Vivo Tracing in the Macaque Visual Cortex

Diffusion magnetic resonance imaging (MRI) allows for the noninvasive in vivo examination of anatomical connections in the human brain, which has an important role in understanding brain function. Validation of this technique is vital, but has proved difficult due to the lack of an adequate gold standard. In this work, the macaque visual system was used as a model as an extensive body of literature of in vivo and postmortem tracer studies has established a detailed understanding of the underlying connections. We performed probabilistic tractography on high angular resolution diffusion imaging data of 2 ex vivo, in vitro macaque brains. Comparisons were made between identified connections at different thresholds of probabilistic connection “strength,” and with various tracking optimization strategies previously proposed in the literature, and known connections from the detailed visual system wiring map described by Felleman and Van Essen (1991; FVE91). On average, 74% of connections that were identified by FVE91 were reproduced by performing the most successfully optimized probabilistic diffusion MRI tractography. Further comparison with the results of a more recent tracer study ( Markov et al. 2012) suggests that the fidelity of tractography in estimating the presence or absence of interareal connections may be greater than this

Visually Driven Activation in Macaque Areas V2 and V3 without Input from the Primary Visual Cortex

Creating focal lesions in primary visual cortex (V1) provides an opportunity to study the role of extra-geniculo-striate pathways for activating extrastriate visual cortex. Previous studies have shown that more than 95% of neurons in macaque area V2 and V3 stop firing after reversibly cooling V1 [1], [2], [3]. However, no studies on long term recovery in areas V2, V3 following permanent V1 lesions have been reported in the macaque. Here we use macaque fMRI to study area V2, V3 activity patterns from 1 to 22 months after lesioning area V1. We find that visually driven BOLD responses persist inside the V1-lesion projection zones (LPZ) of areas V2 and V3, but are reduced in strength by ∼70%, on average, compared to pre-lesion levels. Monitoring the LPZ activity over time starting one month following the V1 lesion did not reveal systematic changes in BOLD signal amplitude. Surprisingly, the retinotopic organization inside the LPZ of areas V2, V3 remained similar to that of the non-lesioned hemisphere, suggesting that LPZ activation in V2, V3 is not the result of input arising from nearby (non-lesioned) V1 cortex. Electrophysiology recordings of multi-unit activity corroborated the BOLD observations: visually driven multi-unit responses could be elicited inside the V2 LPZ, even when the visual stimulus was entirely contained within the scotoma induced by the V1 lesion. Restricting the stimulus to the intact visual hemi-field produced no significant BOLD modulation inside the V2, V3 LPZs. We conclude that the observed activity patterns are largely mediated by parallel, V1-bypassing, subcortical pathways that can activate areas V2 and V3 in the absence of V1 input. Such pathways may contribute to the behavioral phenomenon of blindsight

Differences in processing of 3-D shape from multiple cues in monkey cortex revealed by fMRI

Previous work using fMRI in anesthetized monkeys to investigate the representation of 3-D objects and surfaces suggests a set of candidate areas in monkey cortex for cue-invariant 3-D shape processing (Sereno et al., Neuron, 2002). The present study examines activation overlap for 3-D surface shape defined with 3 different cues by directly comparing activation for the same 3-D shapes in the same monkey subjects. Stimuli consisted of a set of 3-D surfaces defined by dynamic (random dots with motion parallax) and static (shading and contour) shape cues. Each shape defined by a particular cue was paired with a control stimulus consisting of a scrambled or disrupted cue gradient to diminish or abolish an impression of depth. Activation from a comparison of intact to control stimuli revealed regions of common activation (e.g., in superior temporal and intra-parietal sulci) for shape defined by the 3 different cues. However, significant differences between the dynamic and static cues emerged. The extent and strength of activation was greater in area MT for dynamic compared to static cues; whereas the opposite was true in area V4. In addition, while there was significant overlap across the cues in regions of the STS anterior to area MT (FST and mid-anterior STS), in each of these regions there was a greater number of voxels active for shape-from-motion stimuli in the fundus vs. the more lateral aspect of the ventral bank. In turn, the lateral aspect of the ventral bank had a greater number of voxels active for shape-from-shading and -contour compared to shape-from-motion stimuli. Between the regions activated primarily by dynamic or static cues there was a region of convergence activated by all the cues

BOLD sensitivity to cortical activation induced by microstimulation: comparison to visual stimulation

Electrical microstimulation via intracortical electrodes is a widely used method for deducing functions of the brain. In this study, we compared the spatial extent and amplitude of BOLD responses evoked by intracortical electrical stimulation in primary visual cortex with BOLD activations evoked by visual stimulation. The experiments were performed in anesthetized rhesus monkeys. Visual stimulation yielded activities larger than predicted from the well-established visual magnification factor. However, electrical microstimulation yielded an even greater spread of the BOLD response. Our results confirm that the effects of electrical microstimulation extend beyond the brain region expected to be excited by direct current spread

Cue-invariant 3-D shape representation in monkey cortex using fMRI

Previous work using fMRI in anesthetized monkeys investigating the representation of 3-D objects defined by moving random dots or static texture cues revealed the presence of a network of areas responsive to 3-D shape in occipital, temporal, parietal, and frontal cortex (Sereno et al., Neuron, 2002). The goal of the present study was to determine the amount of activation overlap for 3-D surface shape defined with 3 different cues by directly comparing activation for the same 3-D shapes in the same scanning session. Stimuli consisted of a set of 3-D surfaces defined by dynamic (random dots with motion parallax) and static (shading and contour) shape cues. Each shape defined by a particular cue was paired with a control stimulus consisting of a scrambled or disrupted cue gradient. The control stimuli contain the same local information as the original surfaces (motion--dot speed and direction; shading--luminance range and pattern; surface contour--line shape and size). However, the disruption of the cue gradient across the image diminishes or abolishes an impression of depth. Activation from a comparison of intact to control stimuli revealed regions of common activation (e.g., in superior temporal, intra-parietal, and arcuate sulci) for shape defined by the 3 different cues. Our results suggest a set of candidate areas in monkey cortex for cue-invariant 3-D shape processing

Retinotopic activation of macaque area V2 without input from primary visual cortex

The presence of focal lesions in primary visual cortex (V1) provides the opportunity to study the role of extra-geniculo-striate pathways for activating extra-striate visual cortex. Previous studies in the macaque have shown that cells in area V2 stop firing after reversibly cooling V1 (Girard and Bullier, 1989; Schiller et al., 1974). However no studies on long term recovery after V1 lesions have been reported in the macaque. Here we use fMRI of the macaque monkey brain to study the organization of V2 from baseline levels up to 16 months post-lesioning. We find that BOLD responses in the lesion projection zone (LPZ) of area V2 are reduced by 80 \% compared to pre-lesion levels. Surprisingly the retinotopic organization inside the area V2 LPZ is similar before and after inducing the V1 lesion, suggesting that V2 activation is not the result of input arising from nearby non-lesioned V1 cortex. Monitoring of the activity over time after the lesion did not reveal systematic changes in signal amplitude near the LPZ border. We conclude that visually driven activation of extra-striate area V2 as revealed by the BOLD signal is 1) significantly reduced, but still present after depriving it of V1 input, 2) the area V2 LPZ largely retains its original retinotopic organization, and 3) the strength of visual modulation inside the LPZ does not seem to increase significantly up to 16 months post-lesioning. We discuss our findings in the context of parallel pathways in the brain which can activate V2 in the absence of V1 input and may contribute to the behavioral phenomenon of blindsight

Biological motion processing in the macaque-fMRI

Psychophysical and imaging studies in humans have demonstrated specialized mechanisms for the detection of biological motion. Studies in humans, however, are limited in the details of these mechanisms they can reveal. We used functional MRI in the anaesthetized macaque to identify the brain areas involved in the analysis of biological motion and thereby provide electrode-guidance to study these mechanisms in more detail. We used a human point-light walker and a scrambled walker. The latter has identical local motion signals to the intact walker, but its local signals do not combine to a figure of a walking human. In a block-design we alternated these stimuli with periods of no visual stimulation. We recorded the BOLD response in a 4.7T vertical scanner (Bruker, Inc) using gradient-recalled multi-shot multi-slice EPI sequences. 21 horizontal slices covered the whole brain. Voxels were 1x1x2mm, TE =20ms, TR=1058ms. The data were analysed in BrainVoyager (BrainInnovation, Inc). Both the intact walker and the scrambled walker significantly activated early visual areas V1, V2 and the motion areas V3 and MT. More interestingly, we also found activation of areas commonly associated with form analysis such as V4 and the mid-anterior STS. Apparently, these areas are equipped with the neural mechanisms to detect the typical pendular movement associated with biological motion. In our setup, however, the intact walker never activated these areas significantly more than the scrambled walker

Combined neurophysiology and fMRI in the awake monkey

Simultaneous intracortical recordings of neural activity (NA) and BOLD responses in the anaesthetized monkey (Logothetis et al,2001)demonstrated various degrees of correlation between the fMRI data and LFP,MUA and SUA. The present work is a further step in the study of the relationship of BOLD to NA in the behaving monkey in a vertical-bore 7T/60cm scanner equipped with a 38-cm gradient insert (80mT/m,130us, Bruker Inc.). The upright positioning of the animal used in every alert monkey laboratory was also chosen for fMRI to minimize discomfort in the monkeys, expedite their training process, and ensure longer cooperation during psychophysical testing. Here, the monkeys were first trained to perform a fixation task (Wurtz, 1969) using juice as a reward. Stimuli were presented through a fiber-optic system (Silent Vision, FL), and eye movements were measured with the iView eye tracking system (SensorMotoric Inst.,GmbH). During data acquisition suction of juice and body movements were prevented by using a number of pressure and motion sensors and by training the animal to remain relaxed during the observation period. MR-compatible plastic chambers and electrodes made of platinum-iridium coated with glass were used for intracortical recordings. Gradient-induced interference was compensated with custom-made electronics (Patent 01116436.5). Brief pulse stimulation with full-field patterns and small stimuli placed within the receptive field of each recording site was used to elicit cortical responses followed by a BOLD response. The correlation of BOLD to different frequency bands with different spatio-temporal stimulation patterns will be discussed

A network of areas for 3-D shape processing in the anesthetized monkey

Using fMRI in anesthetized monkeys and a variety of computer-generated 3-D objects defined by shading, random dots, texture elements, or silhouettes and presented either statically or dynamically (rotating), we have previously identified 3-D shape-specific areas in occipital (areas VP and V3) and temporal (areas MT and FST; mid-to-anterior STS; and the AMTS) cortices (Sereno et al., Soc. Neurosci. Abstr., 26, 498.11, 2000). The present study investigates representation of 3-D shape from motion parallax using dynamic random dots in brain regions beyond the occipital and temporal lobes. Control stimuli consist of constructed objects with scrambled motion gradients. Such stimuli contain the same local motion information as the original objects, but the disruption of the cue gradient across the image diminishes an impression of depth. Spatially resolved BOLD contrast-based functional images of monkey visual cortex were obtained using a high-field (4.7 T) scanner and multi-shot, multi-slice, gradient-recalled, echo-planar imaging (EPI) sequences (voxel size, 1 x1 x 2 mm). Results showed significant activation in previously identified shape-specific regions of occipital and temporal lobes but also several areas in the intraparietal sulcus and two frontal lobe regions (the FEF and ventrolateral prefrontal cortex). This distributed network of areas cuts across both ventral and dorsal processing streams, reflecting multiple uses for 3-D shape representation in perception, recognition, and action