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

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

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

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

Visualizing global brain networks in the monkey using combined fMRI and electrophysiology

We developed a novel method to visualize neural networks of endogenous activity that contribute to the variability observed in electrophysiological and functional imaging experiments. We compared activity recorded from a single electrode in the visual cortex of anesthetized monkeys with the time course of simultaneously recorded fMRI measurements. The electrophysiological signal we used was the band limited power (BLP) signal of the local field potential (LFP), which we have previously shown to exhibit slow and highly coherent fluctuations over large cortical distances. Whole-brain EPI images were collected in a 4.7 T scanner, while electrical activity was monitored with a single intracortical electrode. The maxima of cross-covariation between the BLP at that electrode and blood oxygen level-dependent (BOLD) signals for each voxel (1x1x2mm) in the imaged volume were used to generate maps of brain regions that were functionally linked with the spontaneous fluctuations on the electrode. We found that electrical activity at a single site was highly correlated with voxels throughout the brain. While covariation magnitude was greatest near the electrode tip, it remained significant even in distant brain regions, with cortical and subcortical sites showing different covariation patterns. Albeit preliminary, these results suggest that the electrophysiologically measured spontaneous activity in the visual cortex may result from large-scale fluctuations in global brain networks

Simultaneous recording of neuronal signals and functional NMR imaging

We recently directly examined the relationship between blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) signals and neural activity by simultaneously acquiring electrophysiological and fMRI data from monkeys in a 4.7-T vertical scanner (Logothetis NK, Pauls J, Augath MA, Trinath T, Oeltermann A. Neurophysiological investigation of the basis of the fMRI signal. Nature 2001;412:150–157). Acquisition of electrical signals in the microvolt range required extensive development of new recording hardware, including electrodes, microdrives, signal conditioning and interference compensation devices. Here, we provide a detailed description of the interference compensation system that can be used to record field and action potentials intracortically within a high-field scanner

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