Science - USA (2022-02-11)

particular spatial locations on the ring but
also to their ordinal rank in the sequence
(first, second, or third). We quantified the in-
fluence of spatial item and ordinal rank on the
neural responses of single neurons during the
late delay period using linear regression, in-

corporating spatial item and ordinal rank as

variables (6 items × 3 ranks = 18 combina-

tions) to fit the calcium signals of individual

neurons. We used the regression coefficients

to measure each neuron’s selectivity to either

item or rank variable ( 17 ).

Disentangled representation of SWM by the

LPFC neural population

To examine whether the high-dimensional

state of LPFC neuron activity reflected a dis-

entangled representation of SWM, we first

obtained vector representations in population

SCIENCEscience.org 11 FEBRUARY 2022•VOL 375 ISSUE 6581 633

ΔF/F

5s 200%

Neuron1

Neuron2

Neuron3

Neuron4

AAV1.Syn.GCaMP6S.WPRE.SV40

Two-photon microscope

PS

AS

100 μm

4

3

1 2

PS

AS

2 mm

123

Rank

0.5

1

Correct rate

0

Monkey 1

Proportion

Rank1

Rank2

Rank3

123

Chosen rank

0

0.5

0.25

0.75

1

0.2s + 0.4s

T1 + Interval

Cue on

T2 + Interval

T3 Delay

0.2s + 0.4s

0.2s 2.5~4s

Saccade to

Target1 Saccade to

Target2 Saccade to

Target3

0.5s

1 2

3

5 4

6

A

B

D E

F

G

100

200

300

Time (s)

Δ

F/F(%)

0

0

1234

T1 Delay

Rank1

Time (s)

01234

T2

Rank2

Time (s)

01234

T3

Rank3

Time (s)

01234

Rank2

T2

Time (s)

01234

Rank3

T3

Time (s)

100

200

300

0

01234

Rank1

T1

Δ

F/F(%)

Delay

123

Rank

0

0.5

1

Length-2

Length-3

Shuffle

Monkey 2

0

0.5

0.25

0.75

Proportion

123456

Chosen item

C 1 2 3 4 5 6

Target item

1 2 3 4 5 6

Target

Fig. 1. Two-photon calcium imaging of macaque LPFCs during a delayed
sequence-reproduction task.(A) Task structure ( 17 ). T1, target 1.
(B) Behavioral performance averaged across imaging sessions. Performance
is shown as a function of ordinal rank in length-2 sequences (blue) and
length-3 sequences (red). Error bars represent SEMs. (C) Spatial location (left)
and ordinal rank (right) error patterns, averaged across the two monkeys.
Location error pattern is shown as a function of spatial location, averaged across
different ranks. Rank error pattern is shown as a function of ordinal rank,

averaged across different spatial locations. Error bars represent SEMs.

(D) Illustration of two-photon calcium imaging of monkey LPFCs ( 17 ). AS,

arcuate sulcus; PS, principal sulcus. (E) An example FOV, indicated by the red

square (left), and its enlargement (right). (F) Normalized calcium traces of four

example neurons [yellow circles in (E)].DF/F, normalized fluorescent intensity.

(G) Two example neurons exhibiting the property of conjunctive coding for

spatial location and ordinal rank. Traces were aligned to cue onset and pooled

across trials according to spatial location and ordinal rank.

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