In this study, the onset of eye and hand movements were temporally decoupled with significant decoupling variance in the patient with cerebellar stroke, whereas the patient with cortical stroke displayed increased hand spatial errors and less decoupling variance. Increased decoupling variance in the patient with cerebellar stroke was primarily due to unstable saccade timing. This instability of saccadic latencies, which included both extremely short and very long latencies, resulted in a lower overall average saccadic latency in the cerebellar patient compared to the cortical patient. These findings highlight intriguing facets of eye-hand dyscoordination in these different lesion locations. Broadly speaking, our results corroborate the general notion that the cerebellum is instrumental to the process of temporal prediction for eye and hand movements, while the cortex is instrumental to the process of spatial prediction [5, 22, 28], both of which are critical aspects of functional movement control.
Even basic point-to-point visually-guided reaching is not a simple information transfer from perception to action but rather requires complex information processing, reflecting the correspondence between visually encoded spatial positions and arm coordinates. As such, visually guided arm movement starts with the transformation of the representation of a localized target from its initial coding in retinal coordinates to a body-centered frame of reference . This body-centered frame of reference is more compatible with the intrinsic coordinates provided by the muscle, joint and skin receptors of the limb. The cerebral network that orchestrates this EHC-relevant activity is embedded within a widely distributed fronto-parietal network [30, 31].
The first step of this visually encoded spatial target transformation process, dependent on robust sensory input, is thought to be circumscribed within the parietal lobe and related to interactions between the superior and inferior parietal lobules (SPL / IPL) . The benefit of multiple connections between SPL and IPL and dorsal and lateral frontal areas is the ability to process eye and hand information in parallel . The outcome of parieto-frontal processing is eye and hand information that is matched to the coordinates needed in their respective motor output domains. The eye-hand network can be broken down neuroanatomically into 5 domains: posterior parietal, anterior parietal, cingulate, frontal and prefrontal cortex . Near the parieto-occipital junction (POJ), the hand-eye integration domain (HEID) of the posterior parietal cortex (PPC), more specifically area Opt (lateral PPC) and the dorsomedial areas V6A and 7 m, contains critical nodes for binding retinal, eye and hand signals. While V6A and 7 m are the main sources of visual input to the arm-dominant SPL domain and the medial intraparietal area (MIP – a subdivision of area 5), area Opt projects to IPL, the eye-dominant domain, including the ventral intraparietal area (VIP), sensitive to motion, and the medial superior temporal area (MST) .
The cortical stroke in Case 2 suggests an impairment in eye-hand coordination that may have resulted from a disrupted connection between the frontal lobe and the superior parietal lobe neural network. Patients with cortical stroke have shown significant variability in the neuroanatomical regions that affect aspects of visually-guided reach performance post-injury. Lesions in both frontal and parietal lobes can create a constellation of limb impairments that include optic ataxia, directional hypokinesia, bradykinesia and hypometria , all of which may relate to the visual control of reaching. While variability has been noted in lesion location, it has been suggested that attention should be focused on independent assessment of the ocular motor and manual motor systems, i.e., the eye and hand, and their relationship [28, 32]. Although investigations in humans have been limited, and knowledge regarding interactions between parietal cortices and frontal motor areas is especially poor, new evidence has suggested that enhanced connectivity between the primary motor cortex and the anterior intraparietal sulcus correlates with enhanced recovery [33, 34].
As related to Case 1 and the role of the cerebellum in EHC, a previous review and study by Miall et al.  suggests that the cerebellum provides a forward model for the motor system, which is used to predict movements generated by a given control signal during movement planning. In this role, the forward model would create time-specific signals forecasting the motion of each motor effector and creating the necessary ‘blueprint’ required to plan the control signals needed for coordinated movement control. This study demonstrated improved manual tracking when eye and hand followed the same spatial trajectory and additional improvement when the eye led the hand by 75 to 100 ms. These findings suggest that the interaction between ocular and manual control systems are synergistic and optimal when dependent on synchronized action or temporal coupling; in addition, spatial congruence between trajectories or spatial coupling of ocular/visual feedback with manual control signals was also beneficial .
Imaging studies further support the concept that the cerebellum plays an important role in visually guided tracking; many suggest that this role is dependent on functions that utilize an internal clock and feed-forward computations to enable predictive control [35,36,37]. A number of regions in the cerebellum are involved in the temporal processing of information. In fact, the deep nuclei of the cerebellum are involved in ‘timing’ circuits with the basal ganglia (REF- Bares). There is also significant involvement in the right cerebellum during timed visual discrimination tasks and the left lateral cerebellum during timed movement generation tasks . Studies have demonstrated increased activation between cerebellar vermis lobuli, hemispheric lobuli, posterior hemispheres and premotor and parietal areas when performing eye-hand reaching movements, as compared to isolated eye or hand movements [8, 38]. Previous reports have also shown impaired dexterity (measured by 9HPT) in patients with virtual cerebellar lesions using repetitive transcranial magnetic stimulation . In non-human primates, cerebellar lesions result in more saccadic eye movements when following a target during a smooth pursuit task, as well as decreased correlations of eye and hand movement .
Our patient with cerebellar stroke displayed shorter, but substantially more variable, saccade latencies, corresponding in turn to larger-variance temporal onset differences between eye and hand movements. This finding appears broadly consistent with previous studies showing impaired temporal coupling of eye-hand movement in patients with cerebellar lesions . The results of our study also show an increased number of saccades in the patient with cerebellar stroke, which is consistent with findings from Sailor et al., in which patients with cerebellar lesions, as compared to controls, make more saccades to reach the target than controls, but an equal number of visually triggered saccades . This may suggest that inappropriate saccades could be suppressed during the preparation of goal-directed saccades in cerebellar lesions .
A detailed study of two patients reporting impaired eye-hand coordination after stroke, one cerebellar and one cortical, supports the perspective that different cortical and cerebellar contributions to normal eye-hand function may result in separable deficits following injury. In a case series, it is difficult to generalize the results to larger populations. Nevertheless, the findings observed here indicate that a larger study with appropriate statistical power could yield significant insight.