DISCUSSION

Rubens (1985) felt that CCS attenuated neglect behavior through induction of a transient “leftward motor bias.” In support, he noted that the effect of this intervention seemed proportional to the amount of facilitation of left lateral gaze. The only patient who failed to improve following stimulation was also the patient who failed to show nystagmus, presumably because of vestibulopathy. Similarly, patients showing partial reversal of neglect dyslexia and the most modest improvements in a target cancellation task were also those who had “minimal” restoration of leftward eye movements. Rubens concluded that CCS acted through opposition of the impact of hemispatial hypokinesia on tests of neglect behavior.

Subsequent research suggests that Rubens' original interpretation may have been too narrow. For example, the work of Vallar and colleagues (1990) demonstrates how cold CCS can favorably alter somatosensory thresholds on a tactile detection task and reduce tactile extinction. In another study, the same researchers showed that CCS attenuates neglect, even on paradigms such as tactile exploration without visual guidance (Vallar et al., 1993). Cappa et al. (1987) reported that CCS temporarily ameliorates both hemiasomatognosia for the weak limb and increases awareness of deficit in patients with dense anosognosia. At least two separate groups have also documented how CCS temporarily attenuates somatoparaphrenic delusions (Bisiach et al., 1991; Rode et al., 1992). In all of these examples, the effect of CCS on behavior does not necessarily require either visual input or motor-exploratory output. Hence, the data persuasively indicate that the impact of CCS on neglect extends far beyond the influence of shifting gaze toward the contralesional hemifield or opposition of hemispatial hypokinesia.

When Rubens published his results, he had no means for directly testing the hypothesis that CCS opposed premotor factors that contribute to neglect behavior. Subsequent methods were developed which, by pitting the location of movement and action against the location of visual perception, provided a crude distinction between so-called intentional neglect (IN) and attentional neglect (AN; Bisiach et al., 1990; Coslett et al., 1990; Tegner & Levander, 1991). Radiographic correlations supported the notion that IN was most commonly associated with injuries to motor association cortex, its subcortical projections, or the target of these projections such as the basal ganglia (Ladavas, 1994). In contrast, the cerebral infarcts in Rubens study all involved portions of the parietal cortex and adjacent posterior association cortex, brain regions most commonly associated with AN. Hence, data from Rubens' original study could be interpreted, albeit through retrospective inference, as supporting the notion that CCS opposed sensory-perceptual factors contributing to the attentional type of neglect.

Using a video-based technique, we directly tested for differential effects of CCS on attentional and intentional neglect. Given the small sample size, the results must be considered preliminary and interpreted conservatively. Nevertheless, we observed intergroup differences on both line bisection and target cancellation tasks. For line bisection, CCS shifted bisection marks to the left for both groups. The mean change produced by stimulation was greater for the AN group than the IN group. However, the latter set included one patient whose performance actually shifted more to the right after stimulation, a result never observed in AN patients. After excluding this individual, intergroup differences were much less pronounced, though the same trend persisted. Differential responsiveness was much more apparent with target cancellation tasks. The AN group greatly improved their performance after CCS while the IN group showed only modest change. Since the latter patients omitted more targets at baseline, the present data cannot exclude the possibility that severity of neglect might actually be the critical determinant of CCS response. However, mean line bisection error was actually greater at baseline for the AN group, providing indirect evidence against this conjecture. Interestingly, IN patients increased target cancellation much more for the ipsilesional side compared to the contralateral side, a phenomenon for which we have no explanation. In aggregate, the data indicate that CCS may modify performance on clinical tests of neglect more for patients with AN than for IN.

While the dichotomy we have drawn between AN and IN is highly simplistic, our results might help integrate the perceptual/premotor framework into other accounts of neglect behavior. For example, if neglect simply resulted from “motor bias” to the right (or away from the left), and had no influence on non-lateralized arousal systems, then CCS should increase cancellation of leftward targets while reducing cancellation of rightward targets. Furthermore, one might predict greater gains for the IN group. Neither situation was observed in the current study. If CCS simply reduces neglect from augmentation of non-specific arousal systems, then CCS should improve target cancellation in both ipsilesional and contralesional space, with a proportionately greater impact on ipsilesional space. According to our data, this may pertain more to patients with IN than AN. Last, if neglect results primarily from disruption of a mental representation of contralesional space and CCS acts to bolster or restore this representation, then target cancellation performance should improve primarily in contralesional space. According to present observations, such an account may pertain primarily to the AN group.

The biological basis for the effect of vestibular input on spatial perceptual processing remains obscure. The relevant anatomy begins with vestibular afferents, synapsing in the thalamus and projecting to a limited number of discrete cortical areas. From radionuclide studies, irrigation of the external auditory canal with warm water reliably leads to increased cerebral blood flow in a discrete portion of the contralateral posterior superior temporal lobe (Friberg et al., 1985). Cortical stimulation studies by Penfield and Jasper (1954) suggested that the pertinent region actually occupies the depths of the Sylvian fissure, medial to the temporal planum. Recently, Brandt and colleagues (1994) found a strong association between abnormal vestibular sensation and injury to the posterior insular cortex and the adjacent superior temporal or transverse temporal gyri. The areas of cerebral cortex receiving vestibular projections therefore appear to be located anatomically adjacent to the inferior-posterior parietal cortex, the most common anatomic correlate of the neglect syndrome. However, anatomic attributes of vestibular cortex may not be as relevant as its functional characteristics, including its interaction with other sensory modalities.

Stimulation of the vestibular system in natural contexts always involves concomitant modulation of activity in multiple convergent sensory channels. Whereas other sensory modalities undertake preliminary analysis of physical properties in relative isolation, the nature of vestibular stimuli (i.e., angular acceleration of the head) guarantees that they are ordinarily yoked to associated visual and somatosensory stimuli. In other words, the vestibular apparatus provides body displacement data that essentially duplicates or copies that induced in somatosensory and visual systems. Microelectrode recordings from vestibular cortex furnish a neuroanatomic substrate for this cross-modal interface, showing that the neurons respond not only to vestibular stimuli, but also to visual and tactile afference (Grusser et al., 1990). Recent PET studies also demonstrate increased blood flow to the perisylvian and supplementary somatosensory areas, basal ganglia, and cingulate cortex contralateral to CCS (Bottini et al., 2001). By means that are not yet clear, input provided through vestibular channels may somehow supplement or supplant other damaged sensory inputs that usually contribute to multimodal egocentric spatial representations (Karnath, 1994). Functional imaging data are also compatible with the interpretation that CCS may ameliorate neglect through activation of other components of the distributed network (e.g., cingulate, basal ganglia) that subserve motor-exploratory aspects of spatial cognition (Heilman et al., 1993; Mesulam, 1998).

Alternatively, the influence of CCS on spatial cognition may also result through depression of activity in other sensory systems. Functional imaging studies provide evidence of a reciprocal interaction between visual and vestibular processing; CCS reduces cerebral blood flow in bilateral striate and extrastriate visual cortex (Bottini et al., 2001). Maximal deactivation occurs in visual association cortex (V2/V3) ipsilateral to stimulation, an observation corroborated physiologically through ipsilateral suppression of alpha power after CCS (Storrie-Baker et al., 1997). Reciprocal suppression may normally serve some role in perceptual functions such as the discrimination between self versus environmental motion (Brandt et al., 1998). After brain damage responsible for neglect, however, relative reduction of early visual operations in the healthy hemisphere may actually facilitate residual contralesional spatial processes in the damaged hemisphere. Such a mechanism could explain why some patients with neglect actually shift their bisection bias beyond midpoint into the “normal” space, a phenomenon not predicted through simple restitution of a distorted representation of space.

Finally, from a clinical perspective, differential responsiveness to specific interventions forms an elementary basis for the development of a more systematized nosology of the neglect syndrome. Failure to account for different neglect types may explain why rehabilitation studies often report equivocal results for a single treatment on a large, presumably heterogeneous group of patients with the neglect syndrome (Robertson et al., 1993). Ideally, greater specificity in the determination of neglect subtypes might lead to more rational grounds for application of tailored interventions and therapies. For example, on the basis that parietal lesions produce deficits primarily in covert or involuntary orientation, Ladavas and colleagues (1994) recently described a successful treatment program that emphasized volitionally directed mechanisms of orientation. To what degree such strategies impact neglect subtypes as defined herein remains an important empirical question.