Fronto-cerebellar circuits and eye movement control: a diffusion imaging tractography study of human cortico-pontine projections.

A possible role of the cerebellum in cognitive function might be revealed through its anatomical connections with specific regions of the cerebral cortex. To understand the kind of information transmitted between the cortex and cerebellum, we studied the connections from six subdivisions of frontal and prefrontal cortex using diffusion imaging tractography. Cortico-pontine fibers travel through the cerebral peduncles and reach the cerebellum by way of a synaptic link in the pontine nuclei. In 19 human data sets, we tracked connections between the cerebral peduncle and left hemispheric masks of the superior frontal gyrus (SFG), precentral gyrus (PcG), middle frontal gyrus (MFG), orbital frontal cortex, and two regions of inferior frontal gyrus, including pars opercularis and pars triangularis. Cortico-pontine fibers arose from the PcG, the caudal/medial SFG and a small region of the MFG in a majority of the subjects analyzed. While these regions do have known roles in cognitive and executive functions, all three are strongly associated with the planning and execution of eye movements. Connections from more ventral prefrontal cortex were negligible, indicating that these regions are only sparsely represented in the circuit. Based on this pattern of connectivity, it is likely that the prefrontal connections to the cerebellum are involved in covert motor operations and the control of eye movements.

Paradoxical inter-hemispheric transfer after section of the cerebral commissures.

Section of the forebrain commissures blocks the normally strong transfer of information between the two cerebral hemispheres. Although memory for a visual or tactile task is restricted to one hemisphere, animals may show high level transfer of a motor habit, and they are typically able to use combinations of eye and hand which require links between the two sides of the cerebral cortex. The evidence for paradoxical transfer is reviewed, as well as experiments that show that the cerebellum is the likely route for the spared communications between the two sides of the brain.

Cerebellum: connections and functions.

In addition to its role in motor control, reflex adaptation, and motor learning, three sorts of evidence have been put forward to support the idea that the cerebellum may also be involved in cognition. Patients with cerebellar lesions are reported to have deficits in performing one or another cognitive task. The cerebellum is often seen to be activated when normal subjects perform such tasks. There are connections to and from areas of the prefrontal cortex that may be involved in cognition. In this paper, we review the anatomical evidence to support the claim. We suggest that there are only minor connections with cognitive areas of the cerebral cortex and that some of the imaging evidence may reflect the cerebellum's role in the control of eye movements rather than cognition.

Classical disconnection studies of the corpus callosum.

The corpus callosum is one of the most prominent fiber systems of the mammalian brain. Early reports of animals in which the callosum was cut, often confused the effects attributable to callosum damage with those caused by lesions of other brain structures. Early clinical reports also failed to establish the role of the callosum in humans. Two sorts of evidence began to reveal the functions of the corpus callosum. People with callosal damage cannot read text presented in the left visual field, and animals in which the callosum is divided, and sensory input restricted to one hemisphere, fail to show interhemispheric transfer of learning. These functional findings are consistent with anatomical and physiological studies of the role of the corpus callosum in communication between the hemispheres.

K.M. Bykov and transfer between the hemispheres.

Experiments in the laboratory of Roger Sperry showed that section of the corpus callosum blocks the normally strong transfer of information between the two hemispheres of the brain. In some of the papers from Sperry's lab, work by Bykov in Pavlov's lab was cited, since he appeared to have found similar results earlier. At the time, the only source on Bykov's experiment that was easily available was an abstract in a German journal. Although Bykov was the author of the paper, he did not write the abstract. The author of the abstract was Mark Serejski. Recently we obtained a copy of Bykov's original article in Russian, and arranged for it to be translated into English. The full article makes it clear that the abstract was somewhat misleading both in the methods and the results of Bykov's study. Here we present an English translations of Bykov's paper and the Serejski abstract, along with comments on the discrepancies between the two.

Independent roles for the dorsal paraflocculus and vermal lobule VII of the cerebellum in visuomotor coordination.

Two distinct areas of cerebellar cortex, vermal lobule VII and the dorsal paraflocculus (DPFl) receive visual input. To help understand the visuomotor functions of these two regions, we compared their afferent and efferent connections using the tracers wheatgerm agglutinin horseradish peroxidase (WGA-HRP) and biotinilated dextran amine (BDA). The sources of both mossy fibre and climbing fibre input to the two areas are different. The main mossy fibre input to lobule VII is from the nucleus reticularis tegmenti pontis (NRTP), which relays visual information from the superior colliculus, while the main mossy fibre input to the DPFl is from the pontine nuclei, relaying information from cortical visual areas. The DPFl and lobule VII both also receive mossy fibre input from several common brainstem regions, but from different subsets of cells. These include visual input from the dorsolateral pons, and vestibular-oculomotor input from the medial vestibular nucleus (MVe) and the nucleus prepositus hypoglossi (Nph). The climbing fibre input to the two cerebellar regions is from different subdivisions of the inferior olivary nuclei. Climbing fibres from the caudal medial accessory olive (cMAO) project to lobule VII, while the rostral MAO (rMAO) and the principal olive (PO) project to the DPFl. The efferent projections from lobule VII and the DPF1 are to all of the recognised oculomotor and visual areas within the deep cerebellar nuclei, but to separate territories. Both regions play a role in eye movement control. The DPFl may also have a role in visually guided reaching.

Cerebellum lesions and finger use.

We tested monkeys, patients, and normal control human subjects in a task that requires skilled use of the fingers. Animals and patients with lesions of the cerebellum, particularly of the cerebellar hemispheres, were severely impaired in retrieving raisins from small holes (monkeys) or shifting beads from place to place through a series of such holes, using the index finger alone or in apposition (humans). As they descend through the pontine nuclei, pyramidal tract fibres give off a collateral to pontine cells. The axons of pontine cells, in turn, project to the cerebellar cortex, where they terminate as mossy fibres. We suggest that the corollary discharge from pyramidal tract fibres to the cerebellum via the pontine nuclei is required for skilled, co-coordinated, simultaneous or sequential movements.

Subcortical projections of the parietal lobes.

Parietal lobe visual areas project to several subcortical targets. Three of the most prominent of these are to the basal ganglia, superior colliculus, and pontine nuclei. All three are probably involved in some aspect of visually guided movement. One of the largest systems of fiber connections in the human brain arises in the cerebral cortex, and relays to the cerebellum via the pontine nuclei. Pontocerebellar axons terminate within the cerebellar cortex as mossy fibers. Cells in the cerebral cortex that project to the pontine nuclei are all pyramidal in shape, and all are located in lamina V of the cerebral cortex. Subcortical projections from the somatosensory cortex of rats shows that cells that project to the basal ganglia and cerebellum occupy different sublaminae of layer V. Some cortical pyramidal cells' axons may divide, with one branch projecting to the superior colliculus, the other to the pontine nuclei. Temporal lobe visual areas, which are involved in form recognition and learning, do not project to the cerebellum. Reciprocal connections from the cerebellum back to the parietal lobe may play a role in converting visual information from retinotopic to head-centered coordinates.