Interhemispheric Functional And Structural Alterations And Their Relationships With Alertness In Unilateral Temporal Lobe Epilepsy

Many studies have shown that temporal lobe epilepsy（TLE）is associated with functional and structural abnormalities at specific brain areas.High degree of correlated activity between homotopic regions has been considered as one of the most salient aspects of the intrinsic functional architecture of the brain.The homotopic connections may reflect the importance of interhemispheric communication to integrate brain function,and have been considered important to depict the physiologic and pathologic features of the brain.Unfortunately,relatively limited information has been presented about the alterations of interhemispheric functional and anatomic connectivity in patients with unilateral TLE.In the present study,we investigated interhemispheric functional connectivity using a voxel-mirrored homotopic connectivity（VMHC）method.We further revealed fractional anisotropy（FA）changes in the areas with abnormal VMHC values in TLE patients by diffusion tensor imaging（DTI）.Moreover,their relationships with alertness in patients with unilateral TLE were also investigated.The First Part【Objective】To investigate the alterations of homotopic connectivity in unilateral temporal lobe epilepsy（TLE）.【Methods】Resting-state functional MR imaging data were acquired from patients with unilateral temporal lobe epilepsy（n=43）[21 left TLE（LTLE）and 22 right TLE（RTLE）]and normal controls（NC）（n=20）.We mainly concerned with the functional connectivity between any pair of symmetric interhemispheric voxels（i.e.,functional homotopy）which were measured by voxel-mirrored homotopic connectivity（VMHC）.【Results】Compared with NC group,the LTLE patients showed increased interhemispheric functional connectivity between the bilateral angular gyri,occipital gyri and superior parietal gyri,and decreased functional connectivity between the bilateral supplementary motor areas,middle temporal gyri,medial frontal gyri and inferior parietal lobules.Compared with control subjects,RTLE patients exhibited increased interhemispheric functional connectivity between bilateral inferior occipital gyri,parahippocampa gyri,cerebellum,as well as decreased functional connectivity between the bilateral middle temporal gyri,precentral gyri and inferior frontal gyri.【Conclusions】The elevations or reductions of VMHC value in some brain regions in TLE suggested that there were changes of the functional synchronization and coordination occurred in the two hemispheres in patients with unilateral TLE.The Second Part【Objective】To characterize interhemispheric anatomic connectivity in patients with unilateral TLE.【Methods】Resting-state functional and structural magnetic resonance images were acquired in 10 LTLE patients,16 RTLE patients and 20 NCs.Homotopic regions showing abnormal functional connectivity in patients were adopted as regions of interest for DTI.The FA values were compared between groups.Two-sample t test were used.【Results】Statistical results indicated that the FA value of the commissural fiber bundles connecting the bilateral hippocampal gyri（t=3.042;P=0.004）was smaller in RTLE patients than NCs.The FA value of the association fibers connecting the bilateral hippocampal gyrus had no significant difference between the LTLE group and NC group.【Conclusions】In the RTLE patients,some of the brain regions which had abnormal interhemispheric functional connectivity had structural damage.The functional and structural damage may be more serious in the right TLE patients than in left TLE patients.The Third Part【Objective】To investigate the correlation between the alerting effect and the FA value of the commissural fiber fibers in bilateral hippocampal gyrus.【Methods】The attention network test（ANT）was performed to all of the participants.Correlation analyses were employed to examine the relationships between FA value of the association fibers in bilateral hippocampal gyrus and alertness performance in 16 in the right TLE patients.【Results】There were significant differences between the LTLE,RTLE and NC groups in reation time（RT）for no cue condition(RT_no-cue)（F=33.264,P<0.001）,RT for double cue condition(RT_double-cue)（F=66.068,P<0.001）and alerting effect（F=27.569,P<0.001）.In the multiple comparisons,both the LTLE and RTLE groups had significantly longer the RT_no-cue,and lower alertness effect than normal controls(RT_no-cue:LTLE VS NC:610.87±24.85ms VS 552.99±26.35ms,RTLE VS NC:604.53±27.15 ms VS 552.99±26.35 ms;RT_double-cue:LTLE VS NC:580.63±23.60ms VS 509.64±22.41ms,RTLE VS NC:582.55±26.21 ms VS509.64±22.41 ms;alertness effect:LTLE VS NC:30.23±5.90ms VS43.34±11.88,RTLE VS NC:22.67±6.89ms VS 43.34±11.88ms).No significant differences of RTs(RT_no-cue and RT _double-cue)and the alertness effect were found between LTLE and RTLE groups（P>0.05）.The correlation analysis revealed that there was a positive correlation between the FA value of the commissural fiber fibers in bilateral hippocampal gyrus and the alerting effect（r=0.555,P<0.05）.【Conclusions】Compared with NC,both LTLE and RTLE patients had decreased alerting effect,but there was no significant difference in alerting effect between the LTLE and RTLE groups.In RTLE,the FA value of the bilateral hippocampal gyrus was positively correlated with the patient’s vigilance effect,which suggested that there was a certain correlation between the hippocampal gyrus and the alert network.Our findings indicated that the bilateral parahippocampal gyrus may be important to the pathophysiology of patients with unilateral TLE.The significant correlation between the FA values and alertness indicated that structural changes were involved in the alterations of the alertness network in unilateral right TLE patients.