The evolution of prefrontal inputs to the cortico-pontine system: diffusion imaging evidence from Macaque monkeys and humans.

The cortico-ponto-cerebellar system is one of the largest projection systems in the primate brain, but in the human brain the nature of the information processing in this system remains elusive. Determining the areas of the cerebral cortex which contribute projections to this system will allow us to better understand information processing within it. Information from the cerebral cortex is conveyed to the cerebellum by topographically arranged fibres in the cerebral peduncle - an important fibre system in which all cortical outputs spatially converge on their way to the cerebellum via the pontine nuclei. Little is known of their anatomical organization in the human brain. New in vivo diffusion imaging and probabilistic tractography methods now offer a way in which input tracts in the cerebral peduncle can be characterized in detail. Here we use these methods to contrast their organization in humans and macaque monkeys. We confirm the dominant contribution of the cortical motor areas to the macaque monkey cerebral peduncle. However, we also present novel anatomical evidence for a relatively large prefrontal contribution to the human cortico-ponto-cerebellar system in the cerebral peduncle. These findings suggest the selective evolution of prefrontal inputs to the human cortico-ponto-cerebellar system.

Quantitative investigation of connections of the prefrontal cortex in the human and macaque using probabilistic diffusion tractography.

The functions of prefrontal cortex (PFC) areas are constrained by their anatomical connections. There is little quantitative information about human PFC connections, and, instead, our knowledge of primate PFC connections is derived from tracing studies in macaques. The connections of subcortical areas, in which white matter penetration and hence diffusion anisotropy are greatest, can be studied with diffusion-weighted imaging (DWI) tractography. We therefore used DWI tractography in four macaque and 10 human hemispheres to compare the connections of PFC regions with nine subcortical regions, including several fascicles and several subcortical nuclei. A distinct connection pattern was identified for each PFC and each subcortical region. Because some of the fascicles contained connections with posterior cortical areas, it was also possible to draw inferences about PFC connection patterns with posterior cortical areas. Notably, it was possible to identify similar circuits centered on comparable PFC regions in both species; PFC regions probably engage in similar patterns of regionally specific functional interaction with other brain areas in both species. In the case of one area traditionally assigned to the human PFC, the pars opercularis, the distribution of connections was not reminiscent of any macaque PFC region but, instead, resembled the pattern for macaque ventral premotor area. Some limitations to the DWI approach were apparent; the high diffusion anisotropy in the corpus callosum made it difficult to compare connection probability values in the adjacent cingulate region.

The kinetics of the BOLD response depend on inter-stimulus time.

Numerous parameters such as subject age, region of activation, and stimulus timing are known to affect the BOLD signal following neural activation. Here, we investigated how differences in the rest time between successive long visual stimuli alter the kinetics of the BOLD signal in the visual cortex. We found that the BOLD rise time varies with the inter-stimulus interval. By taking this into account when performing statistical analyses of BOLD data, we show that a roughly 20% increase in statistical power can be achieved. In addition, the dependence of the BOLD signal rise time on the inter-stimulus interval provides insight into the physiology underlying the post-stimulus undershoot.

Methods for functional magnetic resonance imaging in normal and lesioned behaving monkeys.

Methods for performing functional magnetic resonance imaging (fMRI) studies in behaving and lesioned monkeys using a human MR scanner are reported. Materials for head implant surgery were selected based on tests for magnetic susceptibility. A primate chair with a rigid head fixation system and a mock scanner environment for training were developed. To perform controlled visual studies, monkeys were trained to maintain fixation for several minutes using a novel training technique that utilized continuous juice rewards. A surface coil was used to acquire anatomical and functional images in four monkeys, one with a partial lesion of striate cortex. High-resolution anatomical images were used after non-uniform intensity correction to create cortical surface reconstructions of both lesioned and normal hemispheres. Our methods were confirmed in two visual experiments, in which functional activations were obtained during both free viewing and fixation conditions. In one experiment, face-selective activity was found in the fundus and banks of the superior temporal sulcus and the middle temporal gyrus in monkeys viewing pictures of faces and objects while maintaining fixation. In a second experiment, regions in occipital, parietal, and frontal cortex were activated in lesioned and normal animals viewing a cartoon movie. Importantly, in the animal with the striate lesion, fMRI signals were obtained in the immediate vicinity of the lesion. Our results extend those previously reported by providing a detailed account of the technique and by demonstrating the feasibility of fMRI in monkeys with lesions.

Retinotopic organization and functional subdivisions of the human lateral geniculate nucleus: a high-resolution functional magnetic resonance imaging study.

Functional magnetic resonance imaging (fMRI) has provided intriguing insights into the topography and functional organization of visual cortical areas in the human brain. However, little is known about the functional anatomy of subcortical nuclei. Here, we used high-resolution fMRI (1.5 x 1.5 x 2 mm3) at 3 tesla to investigate the retinotopic organization of the human lateral geniculate nucleus (LGN). The central 15 degrees of the visual field were mapped using periodic flickering checkerboard stimuli that evoked a traveling wave of activity. The contralateral visual hemifield was represented with the lower field in the medial-superior portion and the upper field in the lateral-inferior portion of each LGN. The horizontal meridian was significantly overrepresented relative to the vertical meridian. The fovea was represented in posterior and superior portions, with increasing eccentricities represented more anteriorly. The magnification of the fovea relative to the periphery was similar to that described for human primary visual cortex. The magnocellular regions of the LGN were distinguished based on their sensitivity to low stimulus contrast and tended to be located in its inferior and medial portions. Our results demonstrate striking similarities in the topographic organization of the macaque and human LGN and support accounts of a constant magnification from the retina through the cortex in both species.

The shape of the fMRI BOLD response in children and adults changes systematically with age.

We measured the shape of the BOLD response to visual stimulation in subjects between 7 and 61 years of age. We performed two experiments. In the first experiment, at low temporal resolution (TR = 1 s) and with long stimulus periods, we determined activated voxels in each subject. In the second experiment, at high temporal resolution (TR = 294 ms), we measured the response to an impulse stimulus in these voxels. We found that the shape of the time course changes systematically with age. Among the parameters whose age dependence we determined quantitatively, we found the smallest effect for the latency of the leading edge. Therefore, in order to avoid the potential confounds resulting from this effect, it may be appropriate to use the latency of the leading edge or the peak intensity of the BOLD signal, rather than its trailing edge or the area under the signal, as the salient variable in event-related studies that compare groups of different age.

Intraoperative assessment of aneurysm clipping using magnetic resonance angiography and diffusion-weighted imaging: technical case report.

OBJECTIVE AND IMPORTANCE: To use intraoperative magnetic resonance imaging, including magnetic resonance angiography and diffusion-weighted imaging, to monitor the surgical treatment of a patient with an intracranial aneurysm. TECHNIQUE: Intraoperative imaging was performed with a ceiling-mounted, mobile, 1.5-T magnet (developed in collaboration with Innovative Magnetic Resonance Imaging Systems, Inc., Winnipeg, MB, Canada) that included high-performance 20-mT/m gradients. Pre- and postclipping, intraoperative, T1-weighted, angiographic and diffusion-weighted magnetic resonance images were obtained from a patient with an incidental, 8-mm, anterior communicating artery aneurysm. RESULTS: T1-weighted images demonstrated brain anatomic features, with visible shifts induced by surgery. Magnetic resonance angiography demonstrated the aneurysm and indicated that, after clipping, the A1 and A2 anterior cerebral artery branches were patent. Diffusion-weighted studies demonstrated no evidence of brain ischemia. CONCLUSION: For the first time, intraoperative magnetic resonance imaging has been used to monitor the surgical treatment of a patient with an intracranial aneurysm.