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Neuroscience and Neurosurgery NINDS Summer Internship Program Career Symposium 12 July 2018 Kareem A. Zaghloul, MD, PhD Surgical Neurology Branch, NINDS National Institutes of Health
Neuroscience and Neurosurgery
NINDS Summer Internship Program Career Symposium
12 July 2018
Kareem A. Zaghloul, MD, PhD Surgical Neurology Branch, NINDS
National Institutes of Health
Neuroscience: Research and Clinical Practice
Allen TA and Fortin NJ (2013) The evolution of episodic memory PNAS 110: 10379-10386
Human episodic memory system
CA3
CA1
DG
PER EC PHCHC
Medial Temporal Lobe
Cortical Association Areas Prefrontal Cortex
Epilepsy • ~1% of the population • 1/3 drug resistant • Similar regions • Surgical treatment
Hippocampus
Pre-surgical Localization
Epileptogenic Zone Area of cortex whose removal will lead to seizure freedom
clas
ses
frequency (Hz)
volta
ge (μ
V) 200
0
-200
0 1 2 time (sec)
Intracranial human recordings for epilepsy
Network Local Neuronal Bullmore E and Sporns O (2012) The economy of brain network Buzsaki G and Draguhn A (2004) Neuronal oscillations
in cortical networks. Science 304(5679): 1926-29 organization Nature Reviews Neuroscience 13: 336-349
time (sec)0 1 2 3
200
0
-200volta
ge (μ
V)
Log s
ize (
mm
)
4
3Brain
2
Map 1
Column 0
Layer -1
Neuron-2
Dendrite
-3
Synapse-4
Millisecond Second Minute Hour Day
Log s
ize (
mm
)
4
3 Brain
2
Map 1
Column 0
Layer -1
Neuron -2
Dendrite
-3
Synapse-4
43210-1-2-3 5 76
Scalp EEG & MEG Functional MRIPET
Naturally
ocurring
lesions
TMS
Multi-unit
recording
Single Cell
recording
43210-1-2-3 5 76
Scalp EEG & MEG Functional MRI PET
Naturally
ocurring
lesions
TMS
Multi-unit
recording
Single Cell
recording
Human
Intracranial
Recordings
Millisecond Second Minute Hour Day
Log time (sec)
Human Physiology
Ward, L.M. Synchronous neural oscillations and cognitive Log time (sec) processes. Trends in Cognitive Sciences 7(12): 553-59, 2003
Paired Associates Verbal Episodic Memory Task
COFFEE
HONEST
DOG
TABLE
ORANGE
NAVY
PENCIL
BISHOP
+
3+4=
PENCI
Encoding
Distraction
Retrieval
t
L
Encoding period
0
Single unit recordings from the human cortex
???
+ BEAM CAMEL + FLOOD
RHINO
8+3+5=
RHINO ??? BEAM
1+4+3= 7+3+2=
Encoding
Retrieval
Distraction
Correc
t
Incorr
ect
0.05
Sem
antic
Rel
ated
ness
0.08
Expec
ted
Intrud
ed
-3 -2 -1 0 1 Time (s)
-0.6
-0.4
-0.2
0
0.2
0.4
0.6
Spik
e R
ate
(z)
-1 0 1 2 3 4 Time (s)
Uni
ts
Encoding Retrieval
-0.6
-0.4
-0.2
0
0.2
0.4
0.6
Spik
e R
ate
(z)
-1 0 1 2 3 4 Time (s)
Uni
ts
Encoding
* *
0
Jang et al., (2017) Current Biology, 27: 1700-1705
My Career Path
• Do what you enjoy and what is interesting
• Cut across disciplines
CO
CT
Inhibition
HC
BC
NA
WA
Excitation
OnS OffSOnT OffT Conduction
30
spik
es
s -1
cells
1
200 100
0.4 0.8
My Career Path
• Take the opportunities you come across
Zaghloul KA, et al 2004 time (s)
Th
(3 (6 ZI
STN
SN
0.0Th
Depth (m
m)
t ZI 5.0 (3 (6
50 V 10.0
STN
15.0SN (3 (6
A Mean spike rate (Hz) =6.4 2 220
Nor
mal
ized
Spi
ke R
ate
1.5 1.5 1 1
0.5 0.5 0 0
−0.5 −0.5
0 −20
mV
−40
−60
−80
20 40 60
Waveform Duration (ms) =0.6815 50
60 40
5010
log
ISI
Tria
ls
5 20
3040 30 20
10 10
0 3 1000 −250 0 250 500 900 −250 0 250 500 900
ms
B Mean spike rate (Hz) =3.3
0
−20
Nor
mal
ized
Spi
ke R
ate
2 2 1.5 1.5
1 1
My Career Path
• Your previous experiences do not constrain you, but they can inform you
Zaghloul KA, et al 2009
• You need a team
My Career Path
My Career Path
• Personal
Acknowledgments
John Wittig, Jr ., PhD Julio Chapeton, PhD Vishnu Sreekumar , PhD Tora Bonnevie Rafi Haque Michael Trotta Mostafa El-Kalliny Chris Zawora Cynthia Steinhardt Baltazar Zavala, PhD Robert Yaffe, PhD Anthony Jang Alex Vaz Timothy Sheehan John Cocjin Srikanth Damera
Clinical Epilepsy Service Sara Inati, MD Aaliyah Thiam Matthew Johnson William Theodore, MD Omar Khan, MD
