Discussion
This study investigated the abilities of patients with TLE for path integration, RM and balancing. With their suspected compromised vestibulo-MTL axis, we expected all three abilities to be impaired in TLE. Indeed, the patients in comparison with healthy controls performed worse in all three corresponding tests: (1) TCT, (2) RM test and (3) CBT. No group differences in volumes of relevant brain regions (as seen by VBM) were found.
Deficits in TCT and RM could arise exclusively from an MTL dysfunction,26 that is, these deficits do not necessarily imply a disruption of the assumed vestibulo-MTL axis. Indeed, many prior patient studies reported difficulties in traditional tasks of hippocampal function such as spatial and associative memory in patients with TLE.10 12 However, our data provide a sound level of evidence that patients’ deficits went beyond a mere MTL dysfunction and involved the vestibulo-MTL system. First, the patients with TLE performed worse in the CBT, a specific test of balancing abilities that does not involve any hippocampus-related function. Second, they performed significantly worse in all memory tests that eliminated visual control and, thus, enforced the use of vestibular input. Third, in all of our patients with TLR we found the same functional deficit as in the non-operated patients. Fourth, patients with a general cognitive deficit performed as good as patients without deficit on TCT and RM. Finally, our earlier study indicated that training of the vestibular system leads to improvements in path integration, suggesting a link between the two systems.6 In summary, the current data suggest that the patients’ disruption of the MTL led to vestibular deficits.
The concept of interdependency between the vestibular system and the MTL, particularly the hippocampus, has been well described by earlier studies on animals1 28 29 and humans.2 4–6 30–32 Since deficits in patients with TLE, with no known vestibular disorders (eg, vestibulopathy), in each of the appointed vestibular-dependent tasks (TCT, RM, CBT) were observed in this study, their impaired performance may be attributed to distorted processing of vestibular inputs by spatial orientation centres, located in the hippocampus and surrounding regions. This is in accordance with studies on patients with temporal lobectomy.14 15 However, unlike these studies, we could not find any structural brain changes nor did we notice a performance differences between operated and non-operated TLE patients.
The rotatory chair test has been successfully applied in a number of studies on various patient groups and healthy participants.33–36 Vestibular inputs play a critical role in human angular orientation by providing inertial cues of self-motion; the brain must then convert motion information to distance information, a process which is known to rely on the temporal lobe and associated regions.35 Temporal lobe regions, primarily the hippocampus and the medial entorhinal cortex, also encode spatial information.36–39 Furthermore, it has already been shown that spatial memory becomes impaired in patients with hippocampal atrophy.2 Also, earlier studies could demonstrate a relationship between vestibular function and topographical/spatial memory, centred in the hippocampus.36 40 However, there is a major lack of information on RM abilities in humans, thus preventing us to make a direct comparison. In our still unpublished work, we could observe a better performance on this test by ballet dancers, who use their vestibular system very frequently. This was also true for participants who underwent a 1-month slackline training with closed eyes. Our current study is the first one to report a decrement in RM abilities of patients with TLE, allowing us to speculate about a possible influence of a functional deficit due to TLE itself or alterations of temporal structures due to the epileptogenic lesion on this ability. This may also indicate that relevant temporal structures have lost their capacity to process and store vestibular inputs, signifying limitations in vestibulo-MTL function or impairments in the vestibulo-MTL axis.
There are very few studies on balancing abilities of patients with TLE and none of them used a clinically validated balance test for assessment. One study on drug-resistant TLE reported postural control abnormalities in the patients.41 Moreover, vestibular dysfunction may lead to a deterioration in short-term visuospatial memory, whereby the involved pathways include the hippocampus, among other cortical regions.42 Vice versa, balance training in healthy adults has positive effects on memory and spatial cognition, and an improvement in cardiorespiratory fitness does not seem to be necessary for these cognitive effects to take place.43 Our study results are also in favour of this interdependency between the MTL and balancing skills, with patients with TLE performing much worse on all conditions of the CBT compared with healthy controls. Although we found a significant difference in balancing abilities between the patients with and without cognitive deficits, our data also indicated that one source of this difference might be the age difference between these two groups, which is in accordance with previous studies investigating the effects of age on clinical balancing abilities.27 Neurocognitive and memory deficits are well-accepted impairments especially in patients with TLE. The current results also have direct clinical consequences as they imply that patients with TLE are also at increased risk of vestibular dysfunction, which could result in falls. This assumption needs further investigation since even in neurological wards this deficit may be overlooked.
The question remains what pathology induced the behavioural deficits in the patients. Using VBM we could not find any significant differences between (non-operated) patients with TLE and healthy controls. Also, the patients who had undergone surgery did not perform differently from the non-operated ones. Together, these observations rather speak for a functional than a structural alteration in these patients. Of course alternative explanations for the null results regarding observable anatomical changes need to be considered. First, the sample size was small consisting of only 11 subjects per group. Previous studies on a much larger sample were able to detect volumetric differences between patients with TLE and controls.44 45 Another limitation is heterogeneity of the sample, consisting of patients with and without hippocampal sclerosis, as well as of those who have and who have not undergone a temporal lobectomy. In only four of our non-operated patients, a hippocampal sclerosis was diagnosed—earlier research has demonstrated that VBM-based differences may highly depend on the extent of hippocampal sclerosis.8 45 The remaining task of future studies is to attempt to confirm our findings on a larger and more homogeneous sample. Nevertheless, functional differences on all three behavioural tests were found despite the shortage of volumetric effects, speaking for a dissociation between structural and functional alterations in patients with TLE-.
In conclusion, this study provides a set of evidence of functional interdependency between the vestibular system and brain regions responsible for processing of vestibular inputs, located in the hippocampus and surrounding MTL areas. Patients with TLE, which we had chosen to test our hypotheses, performed significantly worse than healthy controls on all three tasks known to, at least partially, depend on intact inputs from the vestibular system—namely RM, path integration (triangle completion) and CBTs. On the contrary, no significant volumetric brain differences (as seen by VBM) could be detected between the two groups, which might be due to a small and heterogeneous sample. Nevertheless, since behavioural deficits arose despite the absence of structural changes, there could be a dissociation between the two in patients with TLE. For the purpose of simplicity and effortless understanding of similar structural and functional effects anywhere on the pathway between the vestibular system and MTL, we proposed the concept of a ‘vestibulo-MTL’ axis—based on this concept, alterations in one structure should entail disturbances in the other.