4. DISCUSSION
By utilizing a semantic memory paradigm that did not require explicit
word retrieval, we were able to identify different patterns of EEG
oscillations between normal aging versus pathological aging. When
comparing YA and HA groups, no significant behavioral differences were
seen but three within-group condition effects were identified on EEG
measures: differences in (1) theta ERS and (2) alpha ERD between
conditions were observed in YA but not in HA after 500 ms post-stimulus
onset, and (3) a difference in high beta band ERS between conditions in
the HA group but not in YA group during 400-500 ms post-stimulus onset.
When individuals with MCI were compared to HA, they performed worse than
HA across conditions accompanied by two EEG effects: (1) a difference in
low beta ERS between conditions was observed in the HA group but not in
the MCI group during 400-500 ms post-stimulus onset and (2) a difference
in high beta ERS between conditions, divergent in pattern, was noted
between MCI and HA between 224-261 ms post-stimulus onset.
Our behavioral data showed preserved accuracy and RT in the HA group
compared to the YA group consistent with findings from our prior studies
and the literature supporting relatively preserved access to semantic
memory with normal aging, (Chiang et al., 2014; Verhaegen & Poncelet,
2013; Rönnlund et al., 2015). However, differences between YA and HA
groups observed on EEG suggest early age-related changes emerge between
conditions during 400 and 500 ms post-stimulus onset. The HA group
showed differences in high beta between retrieval and non-retrieval
conditions relative to the YA group. High beta has been associated with
retrieval of semantic information (Slotnick et al., 2002; Ferree et al.,
2009; Hart et al., 2013; Lewis & Bastiaansen, 2015; Weiss & Mueller,
2012). Differences across conditions observed in the HA group suggest
recruitment of additional neural resources, mediated by high beta
activity, to support varying demands related to semantic processing
between the two conditions. In contrast to HA, the YA group showed
differences across conditions after 500 ms post-stimulus onset in theta
and alpha frequency power. In particular, consistent with our prior
findings within similar time windows (Chiang et al., 2016; Ferree et
al., 2009; Hart et al., 2013), YA demonstrated increased alpha ERD
during retrieval compared to non-retrieval conditions, which might be
linked to semantic integration of features which lead to object memory
activation. In the subsequent time window (628 to 701 ms post-stimulus
onset), YA had higher theta ERS during non-retrieval compared to
retrieval conditions, which might be related to enhanced search for
potential feature integration prior to making a final judgment (Yes/No
response on button push). In HA, the loss of such differentiation in
theta and alpha responses (as shown in Supplemental Figures 2 & 5)
might suggest age-related neurophysiological alterations on both
retrieval and non-retrieval conditions as processing related to the task
continues. However, these neural alterations in HA at later time frames
do not seem to be enough to impact task performance, which also
implicates that the earlier high beta differential effects in HA may be
a compensatory mechanism to support semantic memory function. Given that
both retrieval and non-retrieval conditions elicited similar magnitude
of changes in neural responses (i.e., alpha ERD and theta ERS) in older
adults, this finding is consistent with the literature that suggests
dedifferentiation and reduced segregation in neural activity in healthy
aging (Koen & Rugg, 2019; Martin et al., 2022).
Our task was able to differentiate the HA group from individuals with
MCI on behavioral task performance as well as EEG measures. Consistent
with our hypothesis, lower accuracy was noted in the MCI group compared
to the healthy older adult group, suggesting impaired semantic memory
performance, which has been reported in our prior studies and the
literature (Chiang et al., 2015; Kraut et al., 2007; Dudas et al., 2005;
Joubert et al., 2021). We also found greater low beta ERS in retrieval
compared to non-retrieval conditions in the HA group but not in the MCI
group in earlier time windows (< 500 ms post stimulus onset).
These findings suggest that while the HA group differentially allocates
neural resources, mediated by low beta, across the two conditions, these
differentiations are lost in the MCI group. Interestingly, within the
first 300 ms post-stimulus onset, both groups showed differences in high
beta power across conditions, albeit different in patterns. While the HA
group had higher high beta power in retrieval compared to non-retrieval
conditions, an opposite direction was observed in the MCI group with
non-retrieval greater than retrieval conditions. It is unclear what this
reverse pattern indicates, but these findings suggest that HA and MCI
groups may use different strategies to retrieve or process semantic
information during the task. Nevertheless, the MCI group shows patterns
of neural oscillations that can be differentiated from the HA group on
the SORT task and these alterations may be indicative of early neural
decompensation, as suggested in prior studies (Woodard et al., 2009;
Barbeau et al., 2012; Pistono et al., 2021).
Overall, with age, there is a shift in differentiation across conditions
(retrieval vs non-retrieval) from slower frequencies (alpha, theta) to
faster frequencies (low and high beta) on the SORT paradigm. The
transition from slower to faster brain oscillatory responses may be a
sign of aging in general. While both normal and pathological aging
effects were specifically identified in high beta power, the YA and HA
groups differed in the time frame of 444-481 ms post stimulus onset,
which is later than the time frame of 224-261 ms which differentiates
the HA and MCI groups. It is possible that alterations in high beta in
the earlier time window is a sign of pathological aging, while high beta
in the later time window reflects normal aging. Given the evidence that
integration of semantic memory was thought to be associated with high
beta frequency (25-30 Hz) activity from both the cortex and thalamus
during the SORT task (Slotnick et al., 2002; Hart et al., 2013), it is
plausible that differential changes in cortico-thalamo-cortical
synchronization (Crosson, 2021) may underlie the changes we found in
high beta frequency in normal versus pathological aging, though during
an earlier time frame. It has been shown that changes in thalamic
function and cortico-thalamo-cortical connectivity can occur in normal
aging (Goldstone et al., 2018; Fama & Sullivan, 2015) as well as in MCI
(Hahn et al., 2016; Zhou et al., 2013; Aggleton et al., 2016). Future
work that combines EEG and MRI techniques would be useful to explore
these possibilities.
Behavioral measures of semantic memory (e.g., semantic/category fluency)
have already shown promising predictive value in risk of progression to
MCI and dementia (Sutin et al., 2019; Gustavson et al., 2020). EEG
markers of semantic memory will provide additional insights given that
neural changes may precede behavioral changes in pathological aging
(Olichney et al., 2002; Jack et al., 2013). An important implication of
our study is that these brain oscillatory responses can potentially be
used as outcome measures to assess efficacy of interventions (e.g.,
cognitive training, pharmacological treatment) in order to gain a
mechanistic view. Furthermore, with the advent of non-invasive brain
stimulation methods, these oscillatory brain responses may serve as
targets that can be modulated directly by electrical stimulation to
stabilize compensatory processes or to interfere pathological processes,
and thus to maintain or even improve cognitive function in aging
populations (Grover et al., 2022).