Global scale mapping

We chose to study the connectivity of cat primary visual cortex because its cortico-cortical circuitry is well understood and is based on extensive neuroanatomical tracing studies. We targeted the border of area 17 and 18 [the vertical meridian near the horizontal meridian (25, 26)] in hopes of visualizing both ipsilateral and contralateral connections. Since INS applied to the surface of the cortex reaches a penetration depth of a few hundred micrometers, it is expected to activate cortico-cortical projection neurons within the superficial layers and apical dendrites of subcortical projection neurons in the deep layers. Thus, based on known anatomy (Fig. 1B and fig. S1), we expected to see activation in the thalamus [lateral geniculate nucleus (LGN) and lateral posterior nucleus and pulvinar (LP-pulvinar complex)], primary cortical targets (areas 17, 18, and 19), and higher cortical areas [areas 20 and 21, AMLS (anterior medial lateral suprasylvian areas), and PMLS (posterior medial lateral suprasylvian areas)]. We also wondered whether polysynaptic circuits would be revealed.

Fig. 1 Global connections revealed by INS stimulation in cat visual cortex. (A) Stimulation paradigm. Each block of INS comprises 20 trials of pulse trains at a single energy. Train duration, 0.5 s; intertrain interval, 35.5 s; pulses, 250 μs; 200 Hz; 0.1 to 1.0 J/cm2 per pulse. (B) Connections of cat area 17/18. Red arrows indicate cat visual projections from area 17 [adapted from (49)]. The color bar shows T statistics for significant voxels in (C) and (D), thresholded at P < 0.01. (C to E) Data from cat #4. (C) Thalamic activations. Left: Stimulation of area 17/18 at 0.3 J/cm2 [red asterisk in (D)] reveals ipsilateral LGN activation. Right: At 0.7 J/cm2, stimulation produces larger ipsilateral activation in LGN and pulvinar (LGN/Pul). In addition, strong activations are seen in contralateral pulvinar and lateral posterior nucleus (LP). (D) Cortical activations in three slices (dorsal, intermediate, and ventral). The red asterisk denotes the stimulation of area 17/18 at 0.7 J/cm2. Significant voxels seen in areas 17, 18, and 19; AMLS; anterior ectosylvian area (AES); and cingulate visual area (CVA). (E) Intensity dependence (average of 20 trials; error bars, SEM). Top: Time courses (left) and amplitudes (right) at the laser tip site in (D). The yellow bar indicates INS onset. Bottom: Response amplitudes at connected ipsilateral 18 and contralateral 17/18 sites in (D).

In these experiments, a 200-μm optical fiber delivered INS pulse trains (250 μs pulse width, 200 Hz, 0.5 s duration, 36 s per trial, and 20 trials per intensity; see Fig. 1A) to the cortical surface. Nondamaging radiant energies (0.1, 0.3, 0.5, 0.7, or 1.0 J/cm2 per pulse) were used. Blocks of different radiant energies were presented in a randomly interleaved fashion. All images were acquired at 1- or 1.5-mm voxel size using a single-shot echo-planar imaging (EPI) on a 7-T MRI system. Responding voxels were identified with a P value threshold at a false discovery rate (FDR) of 10 or 20%.