hippocampus & medial temporal lobe functional neuroanatomy
DESCRIPTION
Hippocampus & Medial Temporal Lobe Functional Neuroanatomy. LIMBIC SYSTEM (cingulate gyrus, PHG, hypothalamus, septal area, nucleus acumbens, orbitofrontal ctx, amygdala). Broca. Maclean. Cingulate Gyrus. Fornix. Ant. Nucleus of Thal. Mamillary Bodies. Septal Nuclei. Subcallosal Gyrus. - PowerPoint PPT PresentationTRANSCRIPT
![Page 1: Hippocampus & Medial Temporal Lobe Functional Neuroanatomy](https://reader035.vdocuments.mx/reader035/viewer/2022062500/5681593e550346895dc67b6f/html5/thumbnails/1.jpg)
Hippocampus & Medial Temporal Lobe
Functional Neuroanatomy
![Page 2: Hippocampus & Medial Temporal Lobe Functional Neuroanatomy](https://reader035.vdocuments.mx/reader035/viewer/2022062500/5681593e550346895dc67b6f/html5/thumbnails/2.jpg)
PHG
MamillaryBodies
HC
LIMBIC SYSTEM(cingulate gyrus, PHG, hypothalamus, septal area, nucleus acumbens, orbitofrontal ctx, amygdala)
Subcallosal Gyrus
Fornix
Cingulate Gyrus
Ant. Nucleus of Thal
Olfactory bulb
Septal Nuclei
Amygdala
Broca Maclean
![Page 3: Hippocampus & Medial Temporal Lobe Functional Neuroanatomy](https://reader035.vdocuments.mx/reader035/viewer/2022062500/5681593e550346895dc67b6f/html5/thumbnails/3.jpg)
The Medial Temporal Lobeand Hippocampus
![Page 4: Hippocampus & Medial Temporal Lobe Functional Neuroanatomy](https://reader035.vdocuments.mx/reader035/viewer/2022062500/5681593e550346895dc67b6f/html5/thumbnails/4.jpg)
What is amnesia?• Loss of memory function
• Two types
– Retrograde amnesia• Loss of previously-acquired (”premorbid”) memories
– Anterograde amnesia• Inability to form new (”postmorbid”) memories
Injury
Time
![Page 5: Hippocampus & Medial Temporal Lobe Functional Neuroanatomy](https://reader035.vdocuments.mx/reader035/viewer/2022062500/5681593e550346895dc67b6f/html5/thumbnails/5.jpg)
(Corkin, Amaral, Gonzalez, Johnson and Hyman J. Neuro, 1997)(Scoville and Milner, 1957)
Patient H.M. and the Human MTL
• Suffered head injury @age 9– Developed severe epilepsy
• Surgeon surgically removed the medial temporal lobe bilaterally
• HM suffered severe anterograde and temporally graded retrograde amnesia
• Spared skill learning
![Page 6: Hippocampus & Medial Temporal Lobe Functional Neuroanatomy](https://reader035.vdocuments.mx/reader035/viewer/2022062500/5681593e550346895dc67b6f/html5/thumbnails/6.jpg)
INTRODUCTIONMedial Temporal Circuitry
Adjacent MTL cortices : Entorhinal (ERC), Perirhinal (PRC) Parahippocampal (PHC)
Hippocampus (HC) proper : Dentate Gyrus (DG), CA3, CA1, and Subiculum (Sub)
PRC
PHC
ERC
Sub
DG CA 3
CA 1
Fornix
![Page 7: Hippocampus & Medial Temporal Lobe Functional Neuroanatomy](https://reader035.vdocuments.mx/reader035/viewer/2022062500/5681593e550346895dc67b6f/html5/thumbnails/7.jpg)
Hippocampal Molecular Mechanisms
• Place cells, head direction cells, grid cells
• Long-term potentiation
• Neurogenesis
• Microcircuitry
![Page 8: Hippocampus & Medial Temporal Lobe Functional Neuroanatomy](https://reader035.vdocuments.mx/reader035/viewer/2022062500/5681593e550346895dc67b6f/html5/thumbnails/8.jpg)
Hippocampal Place Cells
(O’Keefe & Conway,1978; Wilson & McNaughton, 1993, Ekstrom et al., 2003)
Reproduced from Wilson and McNaughton, 1993, Science
![Page 9: Hippocampus & Medial Temporal Lobe Functional Neuroanatomy](https://reader035.vdocuments.mx/reader035/viewer/2022062500/5681593e550346895dc67b6f/html5/thumbnails/9.jpg)
Place Cells, Head Direction Cells, Grid Cells(Hafting et al., 2005; Moser & Moser, 2007)
PRC
PHC
ERC
Sub
DG CA 3
CA 1
Fornix
![Page 10: Hippocampus & Medial Temporal Lobe Functional Neuroanatomy](https://reader035.vdocuments.mx/reader035/viewer/2022062500/5681593e550346895dc67b6f/html5/thumbnails/10.jpg)
Hippocampal Molecular Mechanisms
• Place cells, head direction cells, grid cells
• Long-term potentiation
• Neurogenesis
• Microcircuitry
![Page 11: Hippocampus & Medial Temporal Lobe Functional Neuroanatomy](https://reader035.vdocuments.mx/reader035/viewer/2022062500/5681593e550346895dc67b6f/html5/thumbnails/11.jpg)
Long-Term Potentiation
(Kandel et al., 2000, Principles of Neural Science(Kandel et al., 2000, Principles of Neural Science)
![Page 12: Hippocampus & Medial Temporal Lobe Functional Neuroanatomy](https://reader035.vdocuments.mx/reader035/viewer/2022062500/5681593e550346895dc67b6f/html5/thumbnails/12.jpg)
Long-term potentiation
• Bliss & Lomo (1973) discovered that high-frequency stimulation of neurons in the hippocampus results in lasting increase in synapse strength (known as long-term potentiation, or LTP)
• LTP relies upon a kind of glutamate receptor (NMDA)
• Block LTP – Block Learning
![Page 13: Hippocampus & Medial Temporal Lobe Functional Neuroanatomy](https://reader035.vdocuments.mx/reader035/viewer/2022062500/5681593e550346895dc67b6f/html5/thumbnails/13.jpg)
Hippocampal Molecular Mechanisms
• Place cells, head direction cells, grid cells
• Long-term potentiation
• Neurogenesis
• Microcircuitry
![Page 14: Hippocampus & Medial Temporal Lobe Functional Neuroanatomy](https://reader035.vdocuments.mx/reader035/viewer/2022062500/5681593e550346895dc67b6f/html5/thumbnails/14.jpg)
Hippocampal Neurogenesis
(Li et al., 2000(Li et al., 2000)
![Page 15: Hippocampus & Medial Temporal Lobe Functional Neuroanatomy](https://reader035.vdocuments.mx/reader035/viewer/2022062500/5681593e550346895dc67b6f/html5/thumbnails/15.jpg)
Exercise-induced increases in Dentate Gyrus CBV correlate with Neurogenesis
Pereira A C et al. PNAS 2007
![Page 16: Hippocampus & Medial Temporal Lobe Functional Neuroanatomy](https://reader035.vdocuments.mx/reader035/viewer/2022062500/5681593e550346895dc67b6f/html5/thumbnails/16.jpg)
Blocking Neurogenesis produces Learning Deficits
(Clelland et al., Science, 2009)
![Page 17: Hippocampus & Medial Temporal Lobe Functional Neuroanatomy](https://reader035.vdocuments.mx/reader035/viewer/2022062500/5681593e550346895dc67b6f/html5/thumbnails/17.jpg)
Taxonomy of Long-term Memory Systems
Squire L, Zola S PNAS 1996;93:13515-13522Adapted from Squire, Knowlton 1994
![Page 18: Hippocampus & Medial Temporal Lobe Functional Neuroanatomy](https://reader035.vdocuments.mx/reader035/viewer/2022062500/5681593e550346895dc67b6f/html5/thumbnails/18.jpg)
Episodic Learning & Memory
Personally experienced events within a spatio-temporal Context (Tulving, 1983, 2002)
![Page 19: Hippocampus & Medial Temporal Lobe Functional Neuroanatomy](https://reader035.vdocuments.mx/reader035/viewer/2022062500/5681593e550346895dc67b6f/html5/thumbnails/19.jpg)
INTRODUCTIONMedial Temporal Circuitry
Adjacent MTL cortices : Entorhinal (ERC), Perirhinal (PRC) Parahippocampal (PHC)
Hippocampus (HC) proper : Dentate Gyrus (DG), CA3, CA1, and Subiculum (Sub)
PRC
PHC
ERC
Sub
DG CA 3
CA 1
Fornix
![Page 20: Hippocampus & Medial Temporal Lobe Functional Neuroanatomy](https://reader035.vdocuments.mx/reader035/viewer/2022062500/5681593e550346895dc67b6f/html5/thumbnails/20.jpg)
Imaging the Human Hippocampus is Challenging
![Page 21: Hippocampus & Medial Temporal Lobe Functional Neuroanatomy](https://reader035.vdocuments.mx/reader035/viewer/2022062500/5681593e550346895dc67b6f/html5/thumbnails/21.jpg)
High-Resolution Hippocampal Imaging
HHR Structural (voxel size = .4 x .4 x 3mm)HHR Functional EPI (voxel size = 1.6 x 1.6 x 3 mm)
![Page 22: Hippocampus & Medial Temporal Lobe Functional Neuroanatomy](https://reader035.vdocuments.mx/reader035/viewer/2022062500/5681593e550346895dc67b6f/html5/thumbnails/22.jpg)
High-resolution MRI of the MTL
(Zeineh, Engel, Thompson, Bookheimer Neuroimage, 2001)
(Ekstrom, Bazih, Suthana, (Ekstrom, Bazih, Suthana, Al-Hakim, Ogura, Zeineh, Burggren, Bookheimer. Neuroimag, 2009)
![Page 23: Hippocampus & Medial Temporal Lobe Functional Neuroanatomy](https://reader035.vdocuments.mx/reader035/viewer/2022062500/5681593e550346895dc67b6f/html5/thumbnails/23.jpg)
Current Research Directions
• Encoding vs. Retrieval
• Match/Mismatch or Updated Encoding– Allocentric Spatial Encoding
• Recollection vs. Familiarity
• Pattern Separation / Pattern Completion
![Page 24: Hippocampus & Medial Temporal Lobe Functional Neuroanatomy](https://reader035.vdocuments.mx/reader035/viewer/2022062500/5681593e550346895dc67b6f/html5/thumbnails/24.jpg)
Novelty Encoding Paradigm
Rest
New
Repeat
New
Repeat
New
Rest
Outdoor Indoor
Alternating Blocks of Novel and Repeat Pictures
![Page 25: Hippocampus & Medial Temporal Lobe Functional Neuroanatomy](https://reader035.vdocuments.mx/reader035/viewer/2022062500/5681593e550346895dc67b6f/html5/thumbnails/25.jpg)
Time Series for Subregions
Sustained Late Activation No Activation
Parahippocampal
Fusiform
CA 2, 3, DG CA 1
Subiculum Entorhinal
![Page 26: Hippocampus & Medial Temporal Lobe Functional Neuroanatomy](https://reader035.vdocuments.mx/reader035/viewer/2022062500/5681593e550346895dc67b6f/html5/thumbnails/26.jpg)
Face-Name Association Zeineh et al, Science, 2003
Learn Face-Name Pair
Covert Name Recall
Distractor
Learn
Recall
Learn
Recall
Learn
Recall
Learn
Recall
D D D DRest Rest
Time 7 minutes
![Page 27: Hippocampus & Medial Temporal Lobe Functional Neuroanatomy](https://reader035.vdocuments.mx/reader035/viewer/2022062500/5681593e550346895dc67b6f/html5/thumbnails/27.jpg)
Results
![Page 28: Hippocampus & Medial Temporal Lobe Functional Neuroanatomy](https://reader035.vdocuments.mx/reader035/viewer/2022062500/5681593e550346895dc67b6f/html5/thumbnails/28.jpg)
Performance
Used as a regressionmodel for learningand retrieval.
![Page 29: Hippocampus & Medial Temporal Lobe Functional Neuroanatomy](https://reader035.vdocuments.mx/reader035/viewer/2022062500/5681593e550346895dc67b6f/html5/thumbnails/29.jpg)
Results
![Page 30: Hippocampus & Medial Temporal Lobe Functional Neuroanatomy](https://reader035.vdocuments.mx/reader035/viewer/2022062500/5681593e550346895dc67b6f/html5/thumbnails/30.jpg)
Time Courses
Learn
Recall
![Page 31: Hippocampus & Medial Temporal Lobe Functional Neuroanatomy](https://reader035.vdocuments.mx/reader035/viewer/2022062500/5681593e550346895dc67b6f/html5/thumbnails/31.jpg)
Encoding/Retrieval of Spatial Associations
(Suthana, Ekstrom, Moshirvaziri, Knowlton, Bookheimer in preparation)(Suthana, Ekstrom, Moshirvaziri, Knowlton, Bookheimer in preparation)
![Page 32: Hippocampus & Medial Temporal Lobe Functional Neuroanatomy](https://reader035.vdocuments.mx/reader035/viewer/2022062500/5681593e550346895dc67b6f/html5/thumbnails/32.jpg)
Recollection versus Familiarity
• (R) Recollection - re-experiencing the encoding event at the time of recall, true episodic memory
• (K) - Know - the feeling of familiarity that you’ve seen something before, but not remembering the exact encoding event– Not implicit because it is conscious
![Page 33: Hippocampus & Medial Temporal Lobe Functional Neuroanatomy](https://reader035.vdocuments.mx/reader035/viewer/2022062500/5681593e550346895dc67b6f/html5/thumbnails/33.jpg)
Eldridge et al 2001, 2005: Remember- Know Distinction in HC
![Page 34: Hippocampus & Medial Temporal Lobe Functional Neuroanatomy](https://reader035.vdocuments.mx/reader035/viewer/2022062500/5681593e550346895dc67b6f/html5/thumbnails/34.jpg)
R vs. K• Eldridge et al have shown the HC is
selectively involved in R, not with K.
![Page 35: Hippocampus & Medial Temporal Lobe Functional Neuroanatomy](https://reader035.vdocuments.mx/reader035/viewer/2022062500/5681593e550346895dc67b6f/html5/thumbnails/35.jpg)
Current Research Directions
• Encoding vs. Retrieval
• Match/Mismatch or Updated Encoding– Allocentric Spatial Encoding
• Recollection vs. Familiarity
• Pattern Separation / Pattern Completion
![Page 36: Hippocampus & Medial Temporal Lobe Functional Neuroanatomy](https://reader035.vdocuments.mx/reader035/viewer/2022062500/5681593e550346895dc67b6f/html5/thumbnails/36.jpg)
CA1 region?
• Bilateral CA1 damage results in memory impairments(Zola-Morgan et al., 1986; Sass et al., 1995; Rausch & Babb, 1993)
• Place cells & computational models (McNaughton & Morris 1987; Lee et al. 2004; Levy 1989; Hasselmo & Schnell, 1994; Blum & Abbot,
1996)
PRC
PHC
ERC
Sub
DG CA 3
CA 1
Fornix
![Page 37: Hippocampus & Medial Temporal Lobe Functional Neuroanatomy](https://reader035.vdocuments.mx/reader035/viewer/2022062500/5681593e550346895dc67b6f/html5/thumbnails/37.jpg)
CA1 region?
• Bilateral CA1 damage results in memory impairments(Zola-Morgan et al., 1986; Sass et al., 1995; Rausch & Babb, 1993)
• Place cells & computational models (McNaughton & Morris 1987; Lee et al. 2004; Levy 1989; Hasselmo & Schnell, 1994; Blum & Abbot,
1996)
ERC
DG CA 3
CA 1 = comparator(match/mismatch detector)
![Page 38: Hippocampus & Medial Temporal Lobe Functional Neuroanatomy](https://reader035.vdocuments.mx/reader035/viewer/2022062500/5681593e550346895dc67b6f/html5/thumbnails/38.jpg)
EGOCENTRIC (SSP): “Learn store locations relative to starting point”
ALLOCENTRIC (MSP): “Learn store locations relative to other stores”
Suthana et al., Journal of Neuroscience, 2009
Learning a Cognitive Map(Allocentric Spatial Encoding)
![Page 39: Hippocampus & Medial Temporal Lobe Functional Neuroanatomy](https://reader035.vdocuments.mx/reader035/viewer/2022062500/5681593e550346895dc67b6f/html5/thumbnails/39.jpg)
(Spearman’s ρ = 0.53, p = 0.02, N=18)
Allocentric Egocentric
Suthana et al., Journal of Neuroscience, 2009
![Page 40: Hippocampus & Medial Temporal Lobe Functional Neuroanatomy](https://reader035.vdocuments.mx/reader035/viewer/2022062500/5681593e550346895dc67b6f/html5/thumbnails/40.jpg)
Current Research Directions
• Encoding vs. Retrieval
• Match/Mismatch or Updated Encoding– Allocentric Spatial Encoding
• Recollection vs. Familiarity
• Pattern Separation / Pattern Completion
![Page 41: Hippocampus & Medial Temporal Lobe Functional Neuroanatomy](https://reader035.vdocuments.mx/reader035/viewer/2022062500/5681593e550346895dc67b6f/html5/thumbnails/41.jpg)
Recollection versus Familiarity
• (R) Recollection - re-experiencing the encoding event at the time of recall, true episodic memory
• (K) - Know - the feeling of familiarity that you’ve seen something before, but not remembering the exact encoding event– Not implicit because it is conscious
![Page 42: Hippocampus & Medial Temporal Lobe Functional Neuroanatomy](https://reader035.vdocuments.mx/reader035/viewer/2022062500/5681593e550346895dc67b6f/html5/thumbnails/42.jpg)
R vs. K• Eldridge et al have shown the HC is selectively
involved in R, not with K.
(Eldridge et al., Nature Neuroscience 2000)
![Page 43: Hippocampus & Medial Temporal Lobe Functional Neuroanatomy](https://reader035.vdocuments.mx/reader035/viewer/2022062500/5681593e550346895dc67b6f/html5/thumbnails/43.jpg)
Current Research Directions
• Encoding vs. Retrieval
• Match/Mismatch or Updated Encoding– Allocentric Spatial Encoding
• Recollection vs. Familiarity
• Pattern Separation / Completion
![Page 44: Hippocampus & Medial Temporal Lobe Functional Neuroanatomy](https://reader035.vdocuments.mx/reader035/viewer/2022062500/5681593e550346895dc67b6f/html5/thumbnails/44.jpg)
– Separation of item/episodic representations
– Orthogonolization of sensory input & reduction of interference(Rolls, 1996; Norman & O’Reilly, 2003)
Pattern separation & the Hippocampus
![Page 45: Hippocampus & Medial Temporal Lobe Functional Neuroanatomy](https://reader035.vdocuments.mx/reader035/viewer/2022062500/5681593e550346895dc67b6f/html5/thumbnails/45.jpg)
Felleman & Van Essen (1991)
![Page 46: Hippocampus & Medial Temporal Lobe Functional Neuroanatomy](https://reader035.vdocuments.mx/reader035/viewer/2022062500/5681593e550346895dc67b6f/html5/thumbnails/46.jpg)
High-res fMRI of Human CA3/DG (Bakker, Kirwan, Miller, and Stark, Science 2008)
Hippocampal CA3/DG and Pattern Separation
![Page 47: Hippocampus & Medial Temporal Lobe Functional Neuroanatomy](https://reader035.vdocuments.mx/reader035/viewer/2022062500/5681593e550346895dc67b6f/html5/thumbnails/47.jpg)
Pattern Separation (CA3/DG)
(Clelland et al., Science, 2009) (Leutgeb et al., Science, 2008)
![Page 48: Hippocampus & Medial Temporal Lobe Functional Neuroanatomy](https://reader035.vdocuments.mx/reader035/viewer/2022062500/5681593e550346895dc67b6f/html5/thumbnails/48.jpg)
Conclusions– Proposed Model (Encoding)
PRC
PHC
ERC
DG CA 3
BOLD
Neuronal Firing
![Page 49: Hippocampus & Medial Temporal Lobe Functional Neuroanatomy](https://reader035.vdocuments.mx/reader035/viewer/2022062500/5681593e550346895dc67b6f/html5/thumbnails/49.jpg)
Conclusions– Proposed Model (Retrieval)
PRC
PHC
ERC
Sub
DG CA 3
CA 1
Fornix
BOLD
Neuronal Firing
![Page 50: Hippocampus & Medial Temporal Lobe Functional Neuroanatomy](https://reader035.vdocuments.mx/reader035/viewer/2022062500/5681593e550346895dc67b6f/html5/thumbnails/50.jpg)
Conclusions– Proposed Model (Allocentric / Mismatch Encoding)
PRC
PHC
ERC
Sub
DG CA 3
CA 1BOLD
Neuronal Firing
![Page 51: Hippocampus & Medial Temporal Lobe Functional Neuroanatomy](https://reader035.vdocuments.mx/reader035/viewer/2022062500/5681593e550346895dc67b6f/html5/thumbnails/51.jpg)
HC
Kluver-Bucy SyndromeBilateral Amygdala and Pyriform ctx
(some area 20 and HC)
Subcallosal Gyrus
Fornix
Cingulate Gyrus
MamillaryBodies
Ant. Nucleus
PHGOlfactory bulb
Septal Nuclei
Amygdala
![Page 52: Hippocampus & Medial Temporal Lobe Functional Neuroanatomy](https://reader035.vdocuments.mx/reader035/viewer/2022062500/5681593e550346895dc67b6f/html5/thumbnails/52.jpg)
*Emotional Response:Endocrine relase, autonomic discharge, facial posturing, body set
![Page 53: Hippocampus & Medial Temporal Lobe Functional Neuroanatomy](https://reader035.vdocuments.mx/reader035/viewer/2022062500/5681593e550346895dc67b6f/html5/thumbnails/53.jpg)
The brain’s response to seeing emotional faces
• Face-specific brain region (fusiform face area)
• Seeing emotional faces (fear, anger) increases activity in the emotional system (amygdala)
• No conscious perception is required
• Frontal lobes can control this response
![Page 54: Hippocampus & Medial Temporal Lobe Functional Neuroanatomy](https://reader035.vdocuments.mx/reader035/viewer/2022062500/5681593e550346895dc67b6f/html5/thumbnails/54.jpg)
Single Neuron Recordings in Humans
![Page 55: Hippocampus & Medial Temporal Lobe Functional Neuroanatomy](https://reader035.vdocuments.mx/reader035/viewer/2022062500/5681593e550346895dc67b6f/html5/thumbnails/55.jpg)
(Quian Quiroga Reddy, Kreiman, Koch, & Fried. Nature, 2005)
(Waydo, Kraskov, Quian Quiroga, Fried, & Koch. Journal of Neurosci 2006)
Invariant Representations in the Human MTL
![Page 56: Hippocampus & Medial Temporal Lobe Functional Neuroanatomy](https://reader035.vdocuments.mx/reader035/viewer/2022062500/5681593e550346895dc67b6f/html5/thumbnails/56.jpg)
Improved Electrode Localization
Improved electrode localization and targeting using high-resolution imaging and cortical unfolding
(Ekstrom, Suthana, Behnke, Bookheimer, and Fried, Journal of Neurosurgery, 2009)(Ekstrom, Suthana, Behnke, Bookheimer, and Fried, Journal of Neurosurgery, 2009)
![Page 57: Hippocampus & Medial Temporal Lobe Functional Neuroanatomy](https://reader035.vdocuments.mx/reader035/viewer/2022062500/5681593e550346895dc67b6f/html5/thumbnails/57.jpg)
Target
Lure 1 Lure 2 Lure 3 Lure 4
Pattern Separation in Human CA3/DG
Suthana et al., in preparation