Introduction Crawford, 2000 Avoli et al., 2002; Bertram, 2006; Du et al., 1993; Plate et al., 1993; Rutecki et al., 1989; Spencer and Spencer, 1994 Eichenbaum, 2000 Dodrill, 2002; Helmstaedter et al., 2003 Ivnik et al., 1987; Spiers et al., 2001 Powell et al., 2005 Powell et al., 2007a Frisk and Milner, 1990; Smith and Milner, 1981 functional Johansen-Berg and Behrens, 2006 Parker et al., 2003; Parker and Alexander 2003 Methods Subjects Duncan, 1997 Woermann et al., 1998 Oldfield, 1971 Powell et al., 2006 Baxendale et al., 1998 Table 1 Wieser et al., 2001 MR data acquisition - 1 - 1 - 1 Moran et al., 1999 Diffusion tensor imaging Wheeler-Kingshott et al., 2002 b 2 - 1 δ - 1 b 3 Parker et al., 2003; Parker and Alexander, 2003 Alexander et al., 2002 Tuch et al., 2002 Pierpaoli et al., 1996; Pierpaoli and Basser, 1996 Tractography Parker et al., 2003; Parker and Alexander, 2003 Parker and Alexander, 2003 Powell et al., 2004 http://www.psychology Fig. 1 Neuropsychological tests Coughlan and Hollows, 1985 Baxendale et al., 1998 Table 2 Data analysis χ 2 U http://www.fil.ion.ucl.ac.uk/spm Powell et al., 2006 Parker et al., 2005 Parker et al., 2005 Toosy et al., 2004 vol vol Jutila et al., 2001 t t FA FA Jutila et al., 2001 t t Pearson's correlation test was used to evaluate the evidence for a correlation of hippocampal volume with tract volume and FA, and tract volume with tract FA, ipsilateral and contralateral to the seizure focus. Performance on material specific memory measures was investigated for evidence of a correlation with tract volume and FA in right and left TLE groups, omitting patient 14 because of his atypical language dominance. Results Demographic analysis There was no significant difference in the mean age or gender distribution of participants in the three groups (controls, left TLE, right TLE). There was no significant difference in the age of onset, duration of epilepsy or frequency of CPS and SGS between left and right TLE patients. Qualitative tract analysis Powell et al., 2004 Fig. 2 Fig. 3 Quantitative tract analysis vol F p vol p Table 3 vol FA F p p FA F p p p Correlation of tract volume and FA with pre-surgical material specific memory r p r p Fig. 4 Correlations of hippocampal volumes with tract volumes and tract FA There was no significant correlation between ipsilateral hippocampal volume and ipsilateral tract volumes or FA nor between contralateral hippocampal volumes and contralateral tract volume or FA. Correlation analysis of tract volume with tract FA r p Fig. 5 Discussion Our principal finding was that in TLE the white matter connections of the parahippocampal gyrus ipsilateral to the seizure focus had smaller volumes and decreased FA. This was statistically significant in left but not right TLE patients. Furthermore, in left TLE, decreased FA was associated with poorer performance on both material specific memory measures. These results are consistent with the hypothesis that TLE involves dysfunction and structural changes in a network that includes the parahippocampal gyrus. Powell et al., 2004 Bernasconi et al., 2003; Bonilha et al., 2003 Bernasconi et al., 2004; Bonilha et al., 2004; Keller et al., 2002b,a, 2004 Bernasconi et al., 2004; Bonilha et al., 2004; Keller et al., 2002 Bonilha et al., 2007 Powell et al., 2007 Parahippocampal connections and memory in temporal lobe epilepsy Eichenbaum, 2000 Eichenbaum, 2000; Murray and Bussey, 1999 Brown and Aggleton, 2001; Eichenbaum, 2000 Suzuki et al., 1993 Hermann et al., 1997 Alessio et al., 2004 Figs. 2 and 3 Suzuki et al., 1993; Suzuki and Amaral, 1994 Baxendale et al., 1998; Kalviainen et al., 1997; Lencz et al., 1992 Gadian et al., 1996; Wendel et al., 2001 Lui et al., 2005 Nestor et al., 2004 Ragin et al., 2005 Charlton et al., 2006 Rose et al., 2006 Yoshiura et al., 2002 Alessio et al., 2004 Charlton et al., 2006 Heiervang et al., 2006 Beaulieu, 2002 Alexander et al., 2007 Wieshmann et al., 1999 The association between hippocampal volume and parahippocampal Volume/FA Bonilha et al., 2003 Jutila et al., 2001 Limitations of Study Duvernoy, 1998 Squire, 1991 Conclusion This tractography study has shown disruption of the architecture and atrophy of the connections of the parahippocampal gyrus ipsilateral to the seizure focus in patients with refractory TLE, and these structural changes were associated with memory deficits evident on psychometric testing. This information has both diagnostic and prognostic implications. Larger, longitudinal studies at a higher resolution will enable both sub-regional analysis, and the investigation of other factors that may contribute to neuronal loss and structural changes, and subsequent memory impairment in patients with TLE.