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Brain Midline1
Midline MRI
Brain Diagram
Cerebral Cortex
Parietal
Lobe
Frontal
Lobe
Basal
Ganglia
Thalamus
Pineal
Hypothal. SC
Occiptal
Lobe
Midbrain
IC
Pituitary
Temporal
Lobe
Cerebellum
Pons
Medulla
Corticospinal Tract
Neuron Numbers:
126 Billion in brain
100 Billion in cerebellum
25 Billion in cerebral cortex
1 Billion in rest of brain
Spinal Cord
Cervical
Thoracic
Lumbosacral
arm
muscles
BBB1
Astrocyte Foot Processes
nuc
Capillary
Lumen
Tight Junctions here
Endothelial
Cell
Basement
Membrane
Redrawn after figure on page 76 of "The Blood Brain Barrier" by GW Goldstein and AL Betz (Sci. Amer. 255:74−83, 1986)
CSF Circulation
Subarachnoid
Space
CSF leaving subarachnoid
space and entering the
venous circulation in the
superior sagittal sinus via
arachnoid villi.
endosteal dura
arachnoid
trabeculae
meningeal dura
Superior
Sagittal
Sinus
blood vessel
on top of pia
gyrus
sulcus
Corpus Callosum
Choroid
Plexus
secretes
CSF into
ventricles
Cerebrum
Third Ventricle
Cerebral Aqueduct
Cerebellum
Fourth Ventricle
Brain Stem
CSF leaving ventricles
and entering subarachnoid
space
Dura (solid line)
Spinal Cord
Arachnoid (dashed line)
Pia (dash−dot−dot line)
Vertebrobasilar Circulation
Cerebral Circulation
le
idd
.
lg
nta
Fro
M
tal
ron
F
ior
er
Inf
Inf
s.
.
lg
nta
ro
rF
rio
e
Occipital
Lobe
Rhinal s.
Collateral s.
Parahippocampal g.
(Inferior Temporal s.)
Occipito−Temporal s.
(Fusiform g.)
Occipito−Temporal g.
Inferior Temporal g.
Rectus g.
C
A
H
H
Cut Surface
of Midbrain
Ca
l
ca
rin
e
f.
s.
al
Middle cerebral a.
Perirhinal
Optic X
ipt
Lingula
Piriform
Uncus
Cuneus
Calcarine s.
g.
al
mp
ca s.
g.
o
ral l s.
ipp ral
po
te
ra
rah
tem mpo
Pa Colla
−
o
e
it
−t
al s.
cip
ito
Rhin
Oc ccip
O
Olfactory bulb
Orbital gyri
cc
l s.
.
ls
.
l g pora
ra
po Tem
em r
r T erio l g. l s.
p
rio
ra a
pe Su
po por l g.
u
m
S
Te em ora
le le T mp
d
d
e
id
M Mid or T
ri
fe
In
Precuneus
−o
n
Fro
Paracentral
Lobule
to
r
rio
pe
Su
l g.
ronta
rior F
Supe
s.
ulate
g.
Cing
ulate
Cing
rie
S
s.
tal
Su
pe
rio
Inf r Pa
erio rie
r P tal L
arie ob
ule
t
Angular g. al s.
Supra−
marginal g
Pa
r
o
eri
up
Postcentra
.
lg
nta
Fro
Precentra
l s.
Precentra
l g.
Cen
tral
Postcentra
s.
l g.
Cerebral Circulation Territories
Entorhinal
Parahippocampal
Anterior cerebral a.
Posterior cerebral a.
Glia
During brain
development
astrocytes known
as radial glia act
as scaffolds along
which neurons and
other cells migrate.
Pia
Glia Limitans
protoplasmic
astrocytes in
gray matter
gap junctions
"Reactive" astrocytes
(gliosis)
Neuronal
Injury
swell in
(2)
cytotoxic
edema
A
A
GFAP
MAO
K+
etj
NO
vasodilation
Astrocytes (A) encapsulate
synapses, restricting diffusion
of neurotransmitters. They also
take up GABA, glutamate, and
other neurotransmitters that are
released. In addition, they
remove excess K+ from the
extracellular space by their
"inward rectifier" K+ channels.
Astrocyte foot processes
induce endothelial tight
A
junctions (etj) of BBB.
A
hypertrophy
A
NGF
CNTF
bFGF
S100−β
NO
proliferation
GM−CSF
A
A
M−CSF
IL−1, IL−6, TNFα,TGF β1
ROS, NO, PG
Complement, proteases
synaptic stripping
A
lactate
CO 2
Neuron
NGF, FGF
TGFβ
IL−1
TNFα
M
O
T cells
MHCII
M
proliferation
MHCII
Neuronal
Injury (1)
O
M
bFGF
ECM
MHCII
M
M
ameboid phagocytic
activated state
ramified
"resting" state
Microglia (M) arise from bone marrow
derived monocytes (mesoderm) that
take up residence in CNS where they
serve as "macrophage sentries" that
monitor state of brain and mediate
interactions with immune system.
A
K+
fibrous astrocyte
in white matter
O
Cross section of axon
myelinated by an
oligodendrocyte.
Oligodendrocytes (O) and astrocytes (A) arise from local
proliferation of migratory, common precursor cells from
neuroepithelium (ectoderm) of ventricles and central canal.
Oligodendrocytes can myelinate as many as 50 CNS axons
over the long (+5 yr) and regionally varied period of brain
development.
Neuron
axon from
another
neuron
synapse
nuc.
cell body
axon
dendrites
spines
axon
myelin sheath
axon continues
axon
synaptic vesicles
axon terminal
neurotransmitter
postsynaptic receptors
can open or close ion channels
synaptic cleft
(10 nm)
dendrite
shaft
Spinal Cord Tracts
10 Important Tracts
5 MOTOR
5 SENSORY
Dorsal
Columns
FG FC
DSCT
CST
RST
STT
VSCT
RtST, VST, TST
3 REALLY IMPORTANT Tracts
1 MOTOR
2 SENSORY
Dorsal
Columns
FG FC
CST
STT
Cranial Nerve Organization into Functional Groups
Efferents (E)
Afferents (A)
GSE General Somatic → myotome skeletal muscle
GVA General Visceral ← heart, stomach, etc.
SVE Special Visceral → arch skeletal muscle
SVA Special Visceral ← taste
GVE General Visceral → smooth & cardiac muscle, glands GSA General Somatic ← face
SSA Special Somatic ← cochlea, semicirc. canals
sulcus limitans
IVth Vent.
Alar
GSA
Basal
Alar
GSE
GVA
SVA
GVE
GVA
GSA
GVE
Basal
SSA
SVE
GSE
Spinal Cord
Brain Stem
Sup. Coll.
Inf Olive
SVE
MOTOR
GVE
GSE
Inf. Coll.
NA− (XI, X, IX)
DMN−X
XII
motVII
IS
motV
SS
VI
EW
III
IV
midline
SENSORY
GVA/SVA
GSA
SOL−(XI, X, VII)
SpV
SSA
PrV
VIII
Medulla
Cranial Nerve
III
IV
V
VI
VII
VIII
IX
X
XI
XII
Name
Oculomotor
Trochlear
Trigeminal
Abducens
Facial
Vestibulocochlear
Glossopharyngeal
Vagus
Accessory
Hypoglossal
MesV
Pons
GSE
x
x
SVE
Midbrain
GVE
x
x
GSA
GVA
SVA
SSA
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Lateral Medullary Syndrome (Wallenberg)
Pathways in the Brain Stem
Corticospinal Tract, Dorsal Column/Medial Lemniscus, Spinothalamic Tract
halam
ot
Spin
s
Cru
ct
ic Tra
Pyramid
Medial
Dorsal
Columns
i
ebr
Cer
cus
Lemnis
NG,NC
CST
Medulla
Midbrain
Pons
MLF and Lateral Vestibulospinal Tract
PPRF
descending MLF
6
ascending MLF
4
3
4
3
lateral vestibulospinal tr.
Vestibular nuclei
P
A Semicircular canals
H
PPRF and Ascending MLF
6
PPRF
ascending MLF
Trigeminal
Trigeminal Nerve Organization
Medulla
Pons
Midbrain
Thalamus
Trigeminal pain fibers join spinothalamic tract
VPM
Ventral Trigemino−thalamic tract
(VTT runs with medial lemniscus)
(DTTs run near central tegmental trs.)
crossed Dorsal Trigemino−thalamic tract
midline
uncrossed Dorsal Trigemino−thalamic tract
PrV
SpV
GSA
caudalis
interpolaris
oralis
VPM
MotV (SVE)
MesV
SpV caudalis
relays pain/temp
(like spinothalamic)
PrV relays
proprioception
(like gracilis/cuneatus)
spinal trigeminal tract
Trig. Ganglion
Ia from spindles in muscles of mastication
(afferents of monosynaptic jaw closing reflex,
similar to monosynaptic patellar reflex)
muscles of mastication (1st arch)
Pupillary Light Reflex Circuitry
Superior
Colliculus
Midbrain
Posterior
Commissure
PAG
Pretectal
Area
Edinger−
Westphal
Nucleus
Lateral
Geniculate
III
Optic
Tract
III
Oculomotor Nerve
II
Optic
Nerves II
Ciliary Ganglion
Retina
Eyes
Pupillary Cons.
Adapted from Kourouyan, H. D.. and Horton, J. C., 1997, Transneuronal retinal input to the primate
Edinger−Westphal nucleus. J. Comp. Neurol. 381:68−80.
Locus Ceruleus/Raphe
Cortex
Su
Precen
tral s.
Precen
tral g.
Centra
l s.
Postce
ntral g.
Postce
ntral s.
pe
ri
Intr or Pa
apa
r
riet ietal
al s Lo
bu
Angular g. .
le
Supramarginal
.
ls
ra
Occipital g.
po
.
g m
s.
l
al r Te
r
o o
ra
po
mp eri .
Te Sup al g
em
r
T
r
r
rio
po erio .
pe
m
f lg
e
n
Su
I
T
ra
e
po
dl
id
m
e
M
rT
rio
fe
n
I
Central s.
Paracentral
Superior Frontal g.
Rectus g.
Olfactory bulb
Parahippocampal g.
Rhinal s.
Perirhinal
C
A
Collateral s.
Occipito−Temporal (fusiform) g.
Occipito−Temporal s.
Inferior Temporal g.
Piriform
Optic X
H
H
Entorhinal
Cut Surface
of Midbrain
Parahippocampal
Pa
r.−
O
cc
Ca . s.
lc.
f.
.
ls
ita
rie
t
o−
Oc
Posterior Cingulate g.
te
Subcallosal g.
Orbital gyri
Precuneus
Pa
An
.
late s .
Cingu
g
e
t
ula
ng
Ci
r
rio
Marginal br.
cip
.
lg
nta
o
r
rF
l s.
rio
nta
pe
o
u
r
S
rF
rio
g.
pe
tal
Su
on
r
F
le
dd
s.
Mi
tal
on
g.
r
F
tal
ior
on
r
r
e
F
Inf
or
eri
Inf
Uncus
g.
al
mp .
a
oc
.
ls
lg
ipp era
ora
rah ollat
p
a
P
em
C
−T
ito
p
i
c
Oc
Cuneus
Calcarine f.
Lingula
Cerebellum
Cerebral Cortex
Parietal
Lobe
Frontal
Lobe
Basal
Ganglia
Thalamus
Hypothal. SC
IC
Pituitary
Temporal
Lobe
Pons
Occiptal
Lobe
Pineal
Midbrain
SCP
MCP
ICP
Cortex
Cerebellum
Medulla
Corticospinal Tract
Neuron Numbers:
126 Billion in brain
100 Billion in cerebellum
25 Billion in cerebral cortex
1 Billion in rest of brain
Spinal Cord
Cervical
Thoracic
Lumbosacral
arm
muscles
Thalamus
A
B
Corpus
callosum
Caudate
Lateral
ventricle
A
L
M
Internal
capsule
Dorsal
thalamus
3V
Hypothalamus
Globus
pallidus
Thalamic Organization on Frontal Section
Nuclei
"Compartments"
ANT
LD
A
MDl
R LP
E PUL
T
MDm
MEDIAL
IML
ILN
MID
VA
VL
VPL/VPM
ZI
LG MG
ANT.
Dorsal
LATERAL
3
V
Ventral
METATHALAMUS
Thalamic Inputs on Horizontal Section
Nuclei
VA
AV
VL
B
Inputs
Basal
ganglia
Mamm
body
+
hipp
Superior
cerebellar
peduncle
ILN
MD
VPL/VPM
Medial lemn/
spinothal tr
(VPL)
Sup coll
Sol N
Trigemthal
(VPM)
Pul
Superior colliculus
MG
Inf coll
LG
Central sulcus
Retina
Thalamic Outputs to Cortex
Motor
Somatosensory
Premotor
Prefrontal
VPL
VL
C
VA
MDl−ILN
LP/
PUL
VPL
VL
LP/
PUL
ANT/LD
Visual
LG
MDl−ILN
PUL
Association
Cortex
Auditory
VA
LG
VPM
MG
Cingulatae
sulcus
MDm−MID
OLF
PUL
Calcarine
sulcus
Thal-BG
Genu of
Corpus
Callosum
LV
Caudate
Ant
Putamen
CL
Genu
GP
Post
Thalamus
LV
Splenium of
Corpus
Callosum
Basal Ganglia Circuitry
Premotor/supplementary
motor cortex
Entire cerebral cortex
Striatum
(caudate,
putamen)
GPl
D1
X
direct
D2
HD
Dopaminergic
nigrostriatal
pathway
X
Globus
pallidus
GPm
Internal
capsule
DBS
Ventral anterior/
ventral lateral
thalamus
indirect
Subthalamic nucleus
Movement
PD
Substantia
nigra
excitatory synapse
inhibitory synapse
Direct Pathway (D1 DA receptor, GABA−SP) facilitates movement.
Indirect Pathway (D2 DA receptor, GABA−ENK) inhibits movement.
Parkinson’s Disease (PD): Loss of nigrostriatal dopamine dysfacilitates Direct Pathway
and disinhibits Indirect Pathway, both REDUCING movement (akinesia, bradykinesia).
Deep brain stimulation (DBS) of the subthalamic nucleus is a new therapy for PD
that reduces excitation of GPm, thereby diminishing its inhibitory output, which relieves
akinesia and facilitates movement.
Huntington’s Disease (HD): Selective loss of striatal neurons projecting to GPl reduces
inhibitory effect of Indirect Pathway, INCREASING movement (chorea).
Descending control signals
Gamma
motor neurons
Muscle
spindles
Alpha
motor neurons
Length
Tendon
organs
Force
Muscle
Motor
Servo
Load
(Houk, JC and Rymer, WZ 1981. Neural control of muscle length and tension. Handbook of Physiology.
Section 1. The Nervous System, Vol. II, Motor Control, Part 1. Am Physiol Soc, Bethesda, pp 257−323)
Motor Pathways
CST
RST
ax pr
dist
RtST, VST, TST
(Lawrence, D.G. and Kuypers, H.G.J.M. The functional organization of the motor
system in the monkey, I and II. Brain 91:1−14 and 14−33, 1968.)
Spasticity = exaggerated stretch reflexes and hypertonia,
along with the clasp−knife reflex.
Strictly defined, spasticity is a velocity dependent increase in resistance
of a passively stretched muscle that is often associated with a sudden
melting of resistance during stretch (clasp knife reflex).
Spasticity is caused by an upper motor neuron lesion that interrupts
both the corticospinal tract (CST) and the descending cortical
projections to the brain stem reticular formation cells that give rise to
the dorsolateral reticulospinal tract (DLRtST). The DLRtST descends
in the dorsolateral funiculus and provides tonic inhibition (NE, 5HT)
of spinal interneurons activated by Group II, III, and IV afferents.
RELEASE from this inhibition causes spasticity’s hypertonia and
hyperreflexia because of selective facilitation of FR and FF alpha motor
neurons. The clasp knife reflex occurs because of loss of inhibition of
inhibitory interneurons relaying group II, III, and IV afferent signals
activated at relatively high thresholds.
muscle/joint afferents
Ia
II,III,IV
(high threshold)
Brain Stem
Ret. Form.
Upper
Motor
Neuron
synapse
effects
DLRtST
5HT
NE
+
CST
α
muscle
(see Burke et al., Brain 95:31−48, 1972 for more info.)
Entire Cerebral Cortex
Basal Ganglia Cerebellum
VA−VL
Motor Cortex
Movement in PD and Cerebellar Damage
A. Normal
B. Cerebellar
C. PD
Flowers, K. 1975. Neurology 25:413
layers
Cerebral Cortex Layers
I
II
III
I
II Supragranular = Cortico−cortical
"Association Cortex"
III
IV
IV Granular = Input or "Sensory Cortex"
V
V
Infragranular = Output or "Motor Cortex"
VI
VI
Ipsilateral Cortex
Contralateral Cortex (callosal)
Non−specific (locus ceruleus, raphe, nucleus basalis)
Cortico−cortical
Striatum, Brainstem, Spinal Cord
Thalamus and Claustrum Thalamus
Outputs from cortical layers
Inputs to cortical layers
Cerebral Cortex Cytoarchitecture
46
17
4
18
6
39
Cortex Big Picture
Body
What?
Move
Where?
Speech
Perception
Vision
Hearing
Eyes−Head
Speech
Production
What?
What?
Body
Vision
Eyes−Head
Viscera/Hormones
chiasm
LVF
RVF
EYE
x
LG
OR
Left
Right
Calcarine Cortex
Visual Cortex
The upper and lower banks of the calcarine sulcus are the location of the primary
visual cortex (area 17). It is organized into a map or "representation" of the
contralateral visual field in which the fovea is represented most posteriorly.
Note the UPPER hemifield maps to the LOWER bank of the calcarine sulcus.
Visual Field
Visual Cortex
Cingulate
sulcus
Parieto−
occipital
sulcus
10
Corpus Callosum
9
Calcarine
sulcus
Enlarged view of
pial surface of
"hypercolumn"
that processes
visual input from
one small area of
contralateral visual
field. Hypercolumn
extends from pia to
to white matter.
L
11
9
6
2
5
1
5
20°
7
5° 1 3
2 4
6
8
12
10
R
All cells in a hypercolumn respond to same part of visual field, but each
hypercolumn can be subdivided into two "ocular dominance columns" in which
cells respond more strongly to inputs from left or right eye (L, R). In addition,
each hypercolumn can also be subdivided into many "orientation columns" where
cells respond more strongly to lines or edges with a particular orientation (vertical,
horizontal, or oblique, depicted as short line segments inside hypercolumn).
Finally, each hypercolumn also contains color−sensitive "blobs" (shaded ovals)
where cells respond to color but not orientation. The visual cortex begins process of
making "lines and shapes" out of retinal "points," allowing us to see Seurat’s
famous painting.
odpattern
Cingulate
sulcus
Parieto−
occipital
sulcus
Corpus Callosum
Calcarine
sulcus
Simplified view of overall pattern
of ocular dominance "stripes" in
primary visual cortex. Light band
represents LEFT eye dominance, and
black band represents RIGHT eye
dominance. Small white rectangle
corresponds to hypercolumn on
previous figure. Note that stripes
"flow" into calcarine sulcus and
then reemerge onto cortical surface.
Hypothalamus-Midsag
Mammillo−thalamic tr.
Massa Intermedia
Hypothalamic Sulcus
Posterior N.
Mammillary
Body
Arcuate N.
Median Eminence
Fornix
Paraventricular N.
Anterior Commissure
Anterior N.
Preoptic Area
Lamina Terminalis
Dorsomedial N.
Ventromedial N.
Supraoptic N.
Suprachiasmatic N.
Optic Chiasm
Hypothalamo−Hypophyseal
Portal System
Posterior Lobe
Pituitary Anterior Lobe
Hypothalamus-Xsec
Corpus Callosum
Lateral
Fornix
Ventricle
Ant
Mammillo−
Thalamic Tr.
Thalamus
Internal
Capsule
Putamen
3V
Basal Forebrain
Caudate
Globus
Pallidus
Hypothalamus
Anterior
Commissure
Fornix
Amygdala
Optic Tracts
Limbic System
Posterior
Cingulate
Anterior
Cingulate
CC
Fornix
Ant.
Nuc.
ST
MTT
Hypothalamus
Septal Area
Subcallosal
Gyrus
AC
Mamm.
Body
VMN
Entorhinal
Cortex
Olf. Tr.
Olfactory
Bulb
Piriform
Cortex
Hippocampal
Formation
Amygdala
Hippocampal Trisynaptic Pathway
Tail of Caudate
Temporal Horn
of Lateral
Ventricle
Schaffer
Collaterals
CA3
Fornix
CA1
Lateral
Geniculate
Mossy
Fibers
Dentate
Gyrus
End of Superficial
Layers of Cortex
Subiculum
Perforant Path
Temporal Lobe
white matter
Entorhinal
Cortex
HM
Rectus g.
Shaded area
shows
HM’s
Orbital gyri
Lesion
Olfactory bulb
Rhinal s.
Collateral s.
Parahippocampal g.
(Fusiform g.)
(Inferior Temporal s.)
Occipito−Temporal g.
Occipito−Temporal s.
Inferior Temporal g.
Piriform
Perirhinal
Optic X
C
A
H
H
Ca
lca
Cut Surface
of Midbrain
rin
e
f.
Entorhinal
Parahippocampal
fMRI "hot spot"
for remembered
words and pictures
aphasia
Arcuate Fasciculus
SPL
SFG
PRCG POCG
SMG AG
OC
MFG
STG
IFG
MTG
ITG
Wernicke’s Area
(Perception of Speech)
Fluent aphasia, "word salad"
Auditory Cortex
Broca’s Area
(Production of Speech)
Non−fluent aphasia, "telegraphic" speech
Radersheidt: Contralateral Neglect
Epilepsy EEG
Mechanisms
Synapse on distal dendrite
+
Several systems normally act
to prevent high frequency bursts of
action potentials in neurons. If these
systems are compromised, abnormal,
epileptic activity can occur.
Original Size of EPSP in dendrite
Long electrotonic length of
dendrites normally attenuates
EPSPs so they have relatively
little effect on firing of APs.
Compare
Damaged neurons with shortened,
truncated dendrites generate
larger EPSPs at the critical
soma−initial segment region,
making the cells hyperexcitable.
Astrocyte
Astrocytes take up extra K and
prevent excess depolarization of
neurons. IF K is allowed to accumulate,
its equilibrium potential becomes more
positive, bringing resting potential
closer to threshold.
K+
Attenuated Size of EPSP at soma
GABA _
+
Inhibitory
Interneuron
axon
IPSPs normally inhibit neurons and prevent high
frequency firing of action potentials.
Many anticonvulsants enhance GABA activity.
Recent research has shown that in epileptic hippocampus
some neurons develop abnormal DEPOLARIZING
responses to GABA, further contributing to hyperexcitability.
Pyramidal neurons also have a "natural tendency" to fire in
high frequency bursts of action potentials. An intrinsic
capability to generate long duration, calcium action potentials
contributes to this tendency.
Inherited "channelopathies" due to mutations in genes
for K, Ca, and Na channels and other membrane proteins
also contribute to various types of inherited epilepsies.