Table 1a.

Studies examining white matter associations with cognition

Author & year	Epilepsy syndrome	N	Cognitive domain(s) examined	Approach & ROI(s)	Findings
Chang et al. [2019]	TLE	46 TLE; 33 HC	Verbal memory	Tract-based DTI (SWM of left medial temporal/posterior cingulate & left lateral temporal regions)	Lower FA and higher MD within the SWM of the left medial temporal/posterior cingulate regions explained the most variance in verbal memory scores compared to other imaging measures.
Balachandra et al. [2020]	TLE	81 TLE	Verbal memory	Tract-based DTI (fornix, PHC, UF, & IFOF) and SC of a temporal sub-network	A combination of SC and hippocampal volume yielded the highest accuracy (81%) for classification of memory impaired versus non-impaired TLEs (90% sensitivity and 67% specificity). SC alone outperformed clinical-variables only and hippocampal volume.
Chang et al. [2017]	TLE	14 LTLE; 26 HC	Language	Tract-based DTI (AF & IFOF)	Right-lateralized FA of the AF was associated with right-lateralized language activation on fMRI.
Munsell et al. [2019]	TLE	24 LTLE (left-hemisphere language dominant)	Language	Whole-brain DTI (SC)	Identified a distributed bilateral white matter network of regions (anterior and medial temporal and frontal lobes) associated with naming performance. The model explained 60% of variance in naming performance.
Kaestner et al [2020]	TLE	82 TLE	Language	Tract-based DTI (AF, IFOF, ILF, UF) and SC of a temporal lobe sub-network	The SC model yielded greater AUC (0.73) and classification accuracy for language impaired vs. non-impaired groups (79%) compared to a tract-based model (AUC = 0.54). SC revealed a WM network contributing to language impairment that was widely distributed, bilateral, and mainly lateral temporal.
Kaestner et al [2019]	TLE	85 TLE; 47 HC	Language	Tract-based DTI (AF, ILF)	The language-impaired TLE group had lower FA in the left ILF and left AF compared to HC, but did not differ from the non-language impaired group.
Reyes et al. [2019]	TLE	70 TLE; 46 HC	Language; verbal memory	Tract-based (AF, UF, ILF, & PHC) and whole-brain DTI	The language and memory impaired group and the memory impaired group showed distinct patterns of WM abnormalities relative to HC. Language and memory impaired group had widespread SWM abnormalities and altered global network topology. Language and memory impaired group also had lower FA of the bilateral AF and ILF and the left UF relative to HC. The language-only impaired group had poorer perisylvian network structure relative to the other groups.
O’Muircheartaigh et al. [2011]	JME	28 JME; 24 HC	Language; verbal and visual memory; executive function	Whole-brain DTI	Lower supplementary motor area FA was associated with poorer naming and verbal expression. Lower posterior cingulate cortex FA was associated with poorer set shifting/cognitive flexibility.
Lin et al. [2020]	TLE and FLE	22 FLE; 22 TLE with focal cortical dysplasia; 22 HC	Chinese version of MoCA)	DTI (graph theory)	Higher local efficiency was associated with better MoCA scores in TLE.
Liu et al. [2016]	TLE	10 LTLE; 16 RTLE; 20 HC	MMSE and the Attention Network Test (ANT)	DTI (selected regions based on abnormal functional connectivity)	FA of the commissural fibers connecting the bilateral parahippocampal gyri were smaller in RTLE than in HC. Lower FA of these fibers was associated with poorer performance on a measure of alertness (ANT) in RTLE.
Diao et al. [2015]	TLE	14 LTLE; 15 HC	Executive function; attention	Tract-based DTI (UF)	In LTLE and HC, lower FA of the left UF was associated with poorer executive function/working memory.
Kim et al. [2012]	JME	25 patients with JME; 30 HC	Executive function; attention	Whole-brain DTI	JME performed worse than HC on most executive function tests. However, FA was not significantly correlated with any of the tests.
Reyes et al. [2018]	TLE	32 TLE (16 LTLE); 24 HC	Executive function (set-shifting)	Restriction spectrum imaging (RSI) of inferior and superior fronto-striatal tracts	Lower neurite density of the bilateral inferior fronto-striatal tracts was associated with poorer performance on verbal set-shifting/response inhibition in TLE, which was driven by LTLE.
Vaessen et al [2012]	TLE and FLE	39 patients with frontal or temporal seizure focus; 23 HC	IQ	Whole brain DTI and WM volume; graph theory	Patients with severe cognitive impairment had lower clustering and higher path length compared to HC and patients with little to no cognitive impairment. No differences found in WM volume. Lower IQ was associated with lower clustering and higher path length.
Knake et al. [2017]	JME	20 JME: 20 HC	Verbal & visual memory; executive function; attention; fluency; personality	Whole-brain DTI	No associations found between DTI and neuropsychological measures. Microstructural changes in the cingulum were related to the personality trait agreeableness.
Mirò et al. [2015]	TLE	21 TLE (14 LTLE; 7 bilateral MTS); 15 HC	Verbal & visual memory; perceptual reasoning; language; processing speed	Tract-based DTI and WM volume	TLE patients with bilateral MTS had lower FA and WM volume in temporal and extra-temporal tracts when compared to left TLE and HC but no significant associations were found with neuropsychological scores.
Dinkelacker et al. [2015]	TLE with MTS	22 RLTE (18 with cognitive data); 22 LTLE (18 with cognitive data); 24 HC	Verbal & visual memory; executive function; spatial orientation; IQ	Tract-based DTI (hippocampus as the seed and thalamus as target region)	Higher hippocampal-thalamic connectivity (i.e. higher number of fiber counts) was associated with worse executive function in TLE (primarily in the Trail Making Test); the same relationship held in LTLE and RLTE separately (though uncorrected for multiple comparisons).
Rodríguez-Cruces et al. [2018]	TLE	16 LTLE (7 with MTS); 10 RTLE (8 with MTS); 23 HC	Verbal & visual memory; processing speed; working memory; perceptual reasoning; verbal comprehension	Whole-brain DTI	In LTLE lower FA of the left anterior corona radiata right, superior corona radiata and left external capsule was associated with poorer working memory. Lower FA of the left external capsule was associated with poorer processing speed. Cluster analysis revealed three cognitive profiles (normal, mainly memory-impaired and domain-general impairment) associated with the degree and spread of WM abnormalities.
Rodríguez-Cruces et al. [2020]	TLE	34 TLE; 24 HC	Verbal & visual memory; processing speed; working memory; perceptual reasoning; verbal comprehension	Whole-brain DTI (SC)	Less efficient WM connectome organization was observed in patients with more cognitive impairment. Network topology characterized cognitive performance better than measures of morphometry (e.g. cortical thickness).

AF = arcuate fasciculus; FA = fractional anisotropy; FLE = frontal lobe epilepsy; HC = healthy controls; HS = hippocampal sclerosis; IFOF = inferior frontal occipital fasciculus; ILF = inferior longitudinal fasciculus; JME = juvenile myoclonic epilepsy; LTLE = left TLE; MD = mean diffusivity; MTS = mesial temporal sclerosis; PHC = parahippocampal cingulum; ROI = region of interest; SC = structural connectome; SWM = superficial white matter; TLE = temporal lobe epilepsy; UF = uncinate fasciculus