areas. We took advantage of this by comparing
the activity in high-order category-selective visual
electrodes (i.e., selective to face or place images)
during viewing to the activity in the same re-
cording sites during free recall, when patients
recalled and verbally described the electrodes’
“preferred”and“nonpreferred”images. Image
preference in each electrode was determined by
sorting the different images according to the
HFB amplitude they elicited during viewing
(averaging the response over a time window
of 100 to 500 ms and across the four presenta-
tions). We defined the top 10 items that evoked
the strongest responseduring viewing as the
“preferred”images and the bottom 10 items as
the“nonpreferred”images. In most instances,
the preferred and nonpreferred images also cor-
responded to the electrodes’preferred and non-
preferred categories, respectively (91% of preferred
images also belonged to the electrodes’preferred
category, i.e., face or place). Comparing pre-
ferred versus nonpreferred items (rather than
the face/place categories) enabled us to exclude
“borderline”exemplars that belonged to the
optimal category yet showed a weak activation,
thus enhancing the sensitivity of the analysis.
Furthermore, it enabled extension of the anal-
ysis to additional visual sites, whose content
selectivity was significant but not necessarily
related to a clear categorical division between
faces and places.
Figure 4A indicates the location of cortical
recording sites that showed a significant HFB
(60 to 160 Hz) power increase in response to
picture presentation during the viewing session
[PFDR< 0.05, Wilcoxon signed-rank test com-
paring stimulus response (100 to 500 ms) versus
prestimulus baseline (–400 to–100 ms)]. Visual
electrodes that showed a preferential HFB re-
sponse to pictures of faces or places were re-garded as category-selective (PFDR< 0.05, Wilcoxon
rank-sum test, faces versus places; see meth-
ods). They were typically localized in high-order
visual areas along the ventral visual stream,
lateral and medial to the fusiform gyrus.
To examine the potential role of SWRs in
coordinating reactivation of cortical represen-
tations during recall, we time-locked the activity
in category-selective visual sites to the onset of
hippocampal SWRs. Specifically, we examined
whether those cortical sites were reactivated
during recall-related hippocampal SWRs and
whether the reactivation was content-specific
(i.e., matched content preference during viewing).
Shown in Fig. 4, B to D, are HFB responses in
three representative category-selective record-
ing sites during picture viewing and free recall.
During recollection, these electrodes showed a
small, transient modulation of HFB amplitude
time-locked to the onset of hippocampal SWRNormanet al.,Science 365 , eaax1030 (2019) 16 August 2019 4of14
A
C D
B
Grand average recall response:−5 −4 −3 −2 −1 0 1 2 3 4 5
Time from verbal recall onset (s)−5 −4 −3 −2 −1 0 1 2 3 4 5
Time from verbal recall onset (s)0.20.30.40.50.6Ripple rate (events/sec)high-RR (n = 169)
low-RR (n = 180)0.20.30.40.5Ripple rate (events/sec)n=351 recall eventsTrialsRipples PSTH: picture viewingrepeatednovelTime from picture onset (s)00.51Ripple rate (events/sec)novel
repeated6001200−0.5 0 0.5 1 1.5 2
Time from picture onset (s)−0.5 0 0.5 1 1.5 200.51Ripple rate (events/sec)high-RR images
low-RR imagesSorted items01high-RR low-RR11 4 2 8TrialsRepeated presentations:low-RRhigh-RR1200600Fig. 2. Ripples PSTH during picture viewing and free recall.(A)SWRs
raster plot and PSTH time-locked to the onset of picture presentation
(n= 15 patients, each viewed 28 items × 4 presentation cycles), showing a
transient increase in averaged SWR rate in response to the first but not to
repeated presentations (P< 0.01, cluster-based permutation test). Black
horizontal bars on thexaxis represent stimulus on-periods. (B) Content
selectivity of SWR rate modulation duringrepeated presentations, with specific
images producing a higher SWR rate. Inset shows the mean rate of individual
items computed over the entire stimulus period with SEM across patients.
Ripple rate of high-RR images was on average 3.5 times that of low-RR images.
(C) Grand-average ripples PSTH time-locked to the onset of verbal recall,
showing a significant increase in SWR rateanticipating the onset of verbal report
by 1 to 2 s (P< 0.01, cluster-based permutation test; see fig. S4D). (D)SWR
rate during recall of high-RR and low-RR images (as defined during viewing),
demonstrating recapitulation of the content selectivity observed during viewing
(P< 0.05, cluster-based permutation test). Note again the anticipatory nature
of the SWR rate increase. Shaded areas represent ±1 bootstrap SE computed
over subjects [in (A) and (B)] or recall events [in (C) and (D)]. Gray horizontal
solid/dashed lines represent mean rate (±1 SD) for the same data when SWR
timing was randomly shuffled. Orange bars represent significant time bins.RESEARCH | RESEARCH ARTICLE