Discussion
Graph theory has been proposed for detailed understanding of structural
connectivity between cortical areas (Sporns et al., 2005). In this
study, graph theory revealed that SWI in drug-resistant TLE increased
from beta frequency and had a markedly high level in gamma frequency. A
recent study also found that in patients with focal epilepsy, SWI tended
to increase in gamma frequency (30–45Hz) (Hatlestad-Hall et al., 2021).
Our study presented all the SWI trends from delta to gamma (30–90Hz) in
TLE patients. SWI is used to describe the balance between the local
connectedness and the global integration of a network. Small-world
organization is intermediate between random networks, short overall path
length associated with a low level of local clustering, regular networks
or lattices, and the high-level of clustering, which is accompanied by a
long path length (Vecchio et al., 2014). Hypersynchronous neuronal
activity associated with epilepsy could cause widespread functional
network alterations. The elevated beta and gamma SWI in drug-resistant
TLE may reflect increased post-synaptic activity of local neurons.
Increased neuronal activity changes the ionic environment of neurons and
leads to increased burst firing of neurons (Heinemann et al., 1986;
Jensen et al., 1994). Intensified gamma networks may be related with the
epileptic characteristics and cortical neuron excitation.
Interestingly, we showed that SWI increased at beta frequency in
patients with TLE and cognitive deficits and then markedly declined at
gamma frequencies. The change was significant at 50-70 Hz, compared to
that in patients with normal cognition. The correlation between
gamma-SWI and cognition has been demonstrated in previous studies
(Vecchio et al., 2017; Vecchio et al., 2016), that lower gamma SWI in AD
is associated with better short-term memory and a smaller hippocampal
volume. Graph analysis suggests less efficient interaction and
disconnection between brain regions in patients with Alzheimer’s
disease, and gamma activity is closely correlated with cognitive
functions (Engel et al., 2001). Our study showed that gamma SWI could be
influenced by focal epilepsy, but a comparison between patients with
drug-resistant TLE to eliminate the influence of epilepsy revealed that
gamma SWI was positively correlated with cognition level, especially in
high gamma. Moreover, TLE patients with cognitive deficits may have
reduced efficiency of network communication in gamma bands in the
context of hypersynchronous neuronal activity. Additionally, the alpha
SWI in both TLE groups was not significantly different from that in the
healthy controls, may due to the small sample and multiple test
correction. However, alpha SWI in TLE showed a positive association with
IQ and MQ scores.
Spectral analyses revealed a reduction of spectral power in the alpha
band and increased power in the delta and theta bands in patients with
drug-resistant TLE, compared to healthy controls. Changes in patients
with cognitive impairment were more pronounced. This indicated that the
general EEG was slow in drug-resistant TLE. Increased delta power is
mainly localized over the anterior head, especially in the temporal
region. The results are corresponding to temporal lesions in TLE.
Decreased gamma power was detected in the temporal, central, and frontal
lobes; however, the average rPSD in the entire head was not
significantly different. Previous studies have suggested reduced
resting-state gamma power/synchronization in Alzheimer’s disease (Koenig
et al., 2005; Ribary et al., 1991; Stam et al., 2002). The present study
revealed that interictal EEG without epileptiform discharges in TLE had
lower gamma power in the temporal and frontal regions. No group
differences of gamma power were detected between the TLE groups. But the
gamma-communicating functional network was influenced by cognitive
impairment in TLE.
Pathological changes were significant in epilepsy patients with
cognitive deficits, including Aβ and p-Tau deposition in the resected
hippocampus. The current study showed that amyloid and p-Tau loads were
increased in TLE patients with cognitive deficits compared to patients
with normal cognition. Both Aβ and p-Tau deposits have been documented
in drug-resistant TLE tissue (Gourmaud et al., 2020; Tai et al., 2016).
Increased Aβ1–42 peptide and hyperphosphorylated Tau in the hippocampus
are associated with cognitive deficits and have been reported in
temporal lobe epilepsy (Gourmaud et al., 2020). Aβ peptides play a key
role in Alzheimer’s disease pathogenesis (Karran et al., 2011). The
findings of our and previous studies indicate that Aβ and p-Tau deposits
may be correlated with impaired cognition in drug-resistant TLE. Gamma
frequency entrainment can attenuate amyloid load and improve cognition
in AD and wild-type animal models (Iaccarino et al., 2016; Park et al.,
2020; Tian et al., 2021). Considering these data, we propose that
alterations in gamma frequency may be a potential therapeutic target for
drug-resistant TLE with cognitive deficits.