Targeted brain stimulation to modulate memory in humans...
Transcript of Targeted brain stimulation to modulate memory in humans...
Targeted brain stimulation to modulate memory in humans 353.14/HHH21
Data Collection and Analysis: intracranial EEG / SR = 500,1000 or 1600ms / wavelet decomposition / 50 log-spaced freqs 1-200Hz / Record-only N = 102Stimulation details: 50Hz pulse frequency / 4600ms duration / biphasic 300μs / onset -200ms relative to word presentation. Stimulation N = 52
This work was supported by the DARPA Restoring Active Memory (RAM) program (CooperativeAgreement N66001-14-2-4032). The views, opinions, and/or findings contained in this materialare those of the authors and should not be interpreted as representing the official views orpolicies of the Department of Defense or the U.S. Government.
Experimental Design
Memory success depends on neural processes engaged at the time that items are encoded.
Encoding operations vary in their efficiency from moment tomoment (Kahana 2012).
We asked how direct electrical stimulation modulates brain statesconducive to successful memory encoding.
Using stimulation of intracranial electrodes, we attempt tomodulate neural activity and consequently memory performance(Halgren et al. 1985; Suthana et al. 2012).
How does stimulation’s effect on physiologypredict its effect on memory?
ReferencesHalgren at al. (1985). Brain and Cognition / Haufe et al (2014) NeuroImage Kahana (2012). Foundations of Human Memory / Suthana et al. (2012). NEJM
Task Details: 1600ms presentation / 750-1000ms jittered ISI / 20s distractor / 30s recall 25 lists per session / 12 words per listClassifier Details: L2 penalized logistic regression / spectral power over 1600ms encoding interval / z-scored input patterns / model evaluation leave-one-out by session
Background
Summary
Overall Effects of Stimulation on Behavior
Multivariate Analysis Discriminates Memory States Classifier Predicts Behavioral Effects of Stimulation
Stimulation increases memory performance if delivered in poorencoding states.
Suggests strategies for optimally applying stimulation to affectmemory function.
Evidence for the spectral tilt predicted stimulation’seffects on neural activity.
1Dept of Psychology, University of Pennsylvania; 2Dept of Neurological Surgery, University of California San Francisco Medical Center; 3Depts of Neurology and 4Radiology, Thomas Jefferson University Hospital; 5Dept of Neurology, Mayo Clinic; 6Dept of Neurology, 7Neurosurgery and 8Radiology, Hospital of the University of Pennsylvania; 9Dept of Neurosurgery, Emory University; 10Dept of Neurosurgery, University of Texas Southwestern; 11Dept of Neurology, Dartmouth-Hitchcock Medical Center; 12Dept of Neurosurgery, Columbia University; 13Surgical Neurology Branch, National Institutes of Health
Youssef Ezzyat1, James Kragel1, John Burke2, Deborah Levy1, Logan O’Sullivan1, Paul Wanda1, Michael Sperling3, Greg Worrell5, Michal Kucewicz5, Kathryn Davis6, Timothy Lucas7,Cory Inman9, Bradley Lega10, Barbara Jobst11, Sameer Sheth12, Kareem Zaghloul13, Joel Stein8, Sandhitsu Das6, Richard Gorniak4, Daniel Rizzuto1 & Michael Kahana1
Word Encoding Trial
Cla
ssifi
er O
utpu
tPr
obab
ility
00.20.40.60.8
1
List 1 List 2 List 3 List 4 List 5 List 6 List 7 List 8
False Alarm Rate0.2 0.4 0.6 0.8 1
Hit
Rat
e
0.20.40.60.8
1
AUC = .76
RegionIFG
MFGSFG
MTLCHipp TC IPCSPC OC
Freq
uenc
y (H
z)
2358
13234068
116200
Mod
el-B
ased
Act
ivat
ion
-0.5
-0.25
0
0.25
0.5
False Alarm Rate0.2 0.4 0.6 0.8 1
Hit
Rat
e
0.2
0.4
0.6
0.8
1
Mean AUC: 0.63t(101) = 19.2, P < 10-10
RegionIFG
MFGSFG
MTLCHipp TC IPCSPC OC
Freq
uenc
y (H
z)
2358
13234068
116200
Subs
eque
nt M
emor
y (t-
stat
)
-0.8
-0.4
0
0.4
0.8
LOCK FUR GOLD ......
Low HighLow-High State Difference
RegionIFG
MFGSFG
MTLHipp TC IPC
SPC OC
Freq
uenc
y (H
z)
2358
13234068
116200
Mea
n t-s
tat
-8
-6
-4
-2
0
2
4
6
8
P < 0.003
P < 0.03 P < 0.05
Stim-NoStim Classifier (t-stat)-5 0 5
N
0
2
4
6
8
10
12Mean = 0.67P < 0.01
Low States
-5 0 5
N
0
2
4
6
8
10
12Mean = -1.52
P < 0.001
High States
Stim-NoStim Classifier (t-stat)
Low High
Stim
-NoS
tim N
orm
aliz
ed R
ecal
l
-250
-150
-50
50
150
Preceding State
Serial Position4 8 12
Prob
abilit
y of
Rec
all
0
0.4
0.8
Lag-5 -3 -1 1 3 5C
ond.
Res
pons
ePr
obab
ility
0
0.4
0.8
Stim ListsNoStim Lists
Record-Only
Normalized Stim-No Stim Recall-75 -50 -25 0 25 50 75
# Pa
tient
Stim
ulat
ion
Sess
ions
0
4
8
12
16 Mean = -6.8%P < 0.04
Spectral Tilt (HFA - LFA t-stat)-2 -1.5 -1 -0.5 0 0.5 1
Cla
ssifi
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utpu
t (St
im-N
oStim
)
-0.2
-0.1
0
0.1
0.2
0.3
r(37) = 0.54P < 0.001
Use classifier decodingto estimate brain
state pre-stimulation
Stimulation increases memory performance andmemory state estimates if delivered in low states
Within patient, classifier significantly discriminatessuccessful and unsuccessful memory states
Classifier significantacross patients
Important features for classificationreflect the ‘spectral tilt’ pattern
Stimulation has modest behavioral effects acrossthe group, but some larger effects within individual patients
PreStimData
Recalled Forgotten
TAPEMOLE
DADFLOOD
2+3+1
Encoding
Stimulation Sessions
Freq
uenc
y
Electrode
“MOLE”
LOCK
FUR
...
Freq
uenc
y
Electrode
... ...
Encoding Classification
Pre-stimulation
Post-stimulation
GOLD
HEN
NoStim control
NoStim control
Stim
Distractor
Recall
Sessions
25 N
oStim
Lis
ts
20 S
tim /
5 N
oStim
...
Record Stimulation
...
“FLOOD”
...
Method: Haufe et al (2014) Subsequent Mem. Analysis