In this study, we systematically investigated regional brain volume abnormalities occurring in TLE patients, and the relationship between parietal lobe volumes and visuoperceptual cognitive performance. Our results show significant volume decreases in several brain structures involving both GM and WM regions in this population, as well as close correlations between parietal lobe volume status and visuoperceptual functioning, which have not been strictly established in TLE.
These data provide further evidence that TLE is associated with brain damage beyond the temporal lobe(Jber et al. 2021; Keller and Roberts 2008). The structural changes may indicate a neural network dysfunction that is reflected in cognitive functioning classically understood to be extra-temporal(Neal et al. 2019).
The percentage of drug-resistant patients enrolled was slightly higher than has been reported in the literature(Currie et al. 1971)(Téllez-Zenteno and Hernández-Ronquillo 2012). All participants were assessed using a high-quality, standardized MRI protocol that is commonly performed in epilepsy patients, facilitating reproducibility and interpretation of the results.
As expected, TLE patients showed lower scores in several cognitive domains, including executive functioning, attention, and processing speed, as well as visual memory(Allone et al. 2017). This supports the well-established non-verbal memory impairment known to be present in these patients(Helmstaedter and Kockelmann 2006)(Sheldon et al. 2020). Mean T-scores in visuoperceptual, visuospatial, and visuoconstructive skills were in line with previous evidence indicating normal performance in these cognitive domains(Grant et al. 2008). However, T-scores in the patients included showed a wide distribution, which allowed us to establish more reliable correlations between these cognitive domains and parietal volumes.
Our results are consistent with previously reported volume differences in GM and WM structures and CSF in TLE patients. Although a progressive reduction in cortical thickness has been described in TLE(Galovic et al. 2019)(B. C. Bernhardt et al. 2009), we found no large differences in this parameter between patients and the control group. Patterns of cortical thickness loss seem to vary depending on the type of epilepsy and its lateralization(Galovic et al. 2019); hence, it could be more difficult to detect cortical thinning in smaller and more heterogeneous groups of patients. As to the sGM structures, our results are consistent with previous evidence showing hippocampal atrophy in TLE patients(Riederer et al. 2020). The findings also provide further evidence of demonstrable atrophy in extratemporal regions, such as the putamen(Kim et al. 2016). There is currently very little evidence of accumbens volume loss in TLE patients(Wang et al. 2017) as was seen here, although there is some data from animal models(Fu et al. 2018).
Several correlations were found between the global and regional WM volume loss and poorer cognitive performance, particularly executive functioning. In contrast, cortical thickness showed weaker and even inverse correlations with cognitive function. Evidence in Alzheimer’s disease has suggested that cortical atrophy in itself may be a poorer predictor of global cognitive decline than other biomarkers(Hedderich et al. 2020). Disrupted WM integrity has also been widely described in epilepsy patients(Tsuda et al. 2018), and our results sustain the idea that this neural network disturbance underlies the global cognitive dysfunction observed in TLE (Chang et al. 2019).
Also as expected, a larger percentage of correlations between parietal WM volume loss and poorer visuoperceptual functioning were found in patients with right-onset TLE. Thus, WM status in this region seems to be more highly implicated in these cognitive functions(De Schotten et al. 2011). Previous functional neuroimaging studies have shown that the superior and inferior parietal cortex are involved in visuospatial skills (Seydell-Greenwald et al. 2017), but specific correlations have not been assessed to date in TLE patients.
In line with previous studies, the right posterior cingulate correlated with visuospatial and visuoconstructive skills(Leech and Sharp 2014). We also found that the precuneal region correlated with visuoperceptual, visuospatial, and visuoconstructive skills. Interestingly, structural and metabolic abnormalities in this region have been associated with poorer performance in constructional praxis skills in patients with early Alzheimer’s disease (Hedderich et al. 2020). Our results provide support that the cingulum and precuneus are both implicated in the visuoperceptual network of these patients. Furthermore, these correlations could represent an interindividual diversity in the established damage in parietal regions, which could underlie the contrasting findings for visuoperceptual impairment in previous analyses(Grant et al. 2005)(Grant et al. 2008).
Our study has limitations. The relatively small sample size and the cross-sectional design may have prevented us from elucidating certain findings in further detail. In addition, our sample included TLE of several etiologies and a high percentage of patients were receiving two or more ASDs, which might have influenced the structural and cognitive correlations described. Further studies including larger samples of non-lesional and strictly unilateral epilepsies would be useful to confirm these results.