Brain Stem

RS3030 R5302 CNN

Sam Chan
samcc.chan@polyu.edu.hk
Tips to Study Neural Structures
• Structures appear in different systems (do not get
overwhelmed)
• Study structures in 2-D / 3-D manner (do not study structures
in isolation)
• Study structures in relation to FUNCTIONS (and dysfunctions)
• Make use of Mnemonics
 Brainstem Cerebrum (Telencephalon*)
Prosencephalon*
Thalamus
(part of diencephalon*)
◼Midbrain
(mesencephalon*)
◼ Pons Cerebellum (part of metencephalon*)
(part of metencephalon*)
Rhombencephalon
◼ Medulla oblongata
(myelencephalon*) Spinal Cord
(* Embryonic Structures)

OUTLINE
• “Rule of 4” of the • Regional Transverse
Brainstem (Gates, 2005) Sections
• Longitudinal Sections • Midbrain
• Tracts • Pons
• Reticular Formation • Medulla
• Clinical Disorders
Key Functions of Brain Stem
➢ Provides the main motor and sensory innervation to the
face and neck via the cranial nerves (Wk 4 Lecture).
➢ Connects the motor (efferent) and sensory (afferent)
systems from the main part of the brain to the rest of the
body.
➢ Regulates the CNS, and is pivotal in maintaining
consciousness and regulating the sleep cycle.
➢ Plays an important role in the regulation of cardiac and
respiratory function (ANS - Wk 4 Lecture).
Anterior and Lateral Views of
Brainstem
Posterior View of Brainstem
Basic
Tectum
Strucrure of
Brain Stem

1. Roof Plate
2. Tegmentum
3. Basal Portion

A: Midbrain
B: Pons
C: Upper Medulla
D: Lower Medulla
Basal Section
• Contains mainly motor
structures
• Descending axons from the Substantia nigra
cerebral cortex
• Corticospinal, corticobulbar,
conticopontine, and
corticoreticular tracts
• Motor nuclei
• Red Nucleus (MB)
• Substantia nigra (MB)
• Pontine nuclei, & inferior olive
(Mdl)
• Pontocerebellar axon
Tegmentum
• Sensory nuclei & ascending
sensory tracts
• Integrating sensory
information
• Cranial nerve nuclei
• Reticular formation
• Adjusting the general level
of neural activity
• Medial longitudinal
fasciculus (MLF)
• Eye & head movement
• Connections between
oculomotor nerve (III),
trochlear nerve (IV), and
abducens nerve (VI) for eye
movement.
Tectum
• Pretectal area
• Superior & inferior
colliculi
• Extrinsic and intrinsic
Eye reflexes and
reflexive head
movements
Summary: Vertical Tracts in Brain Stem
Vertical Tract Modification (Synapse) of Tract
Sensory (ascending)
(Neo)spinothalamic Not modified, i.e. no synapse
Dorsal Column Axons synapse in nucleus gracilus / cuneatus, cross
midline to form medial lemnicus
Spinocerebellar Axons enter cerebellum via inferior / superior peduncles
Motor(descending)
Corticospinal Not modified, i.e. no synapse
Corticobulbar Axons synapse with cranial nerve nuclei
Corticopontine Axons synapse with nuclei in the pons
Corticoreticular Axons synapse with the reticular formation
Autonomic (descending)
Sympathetic Not modified, i.e. no synapse
Parasympathetic Axons synapse with parasympatheic nuclei or continue
via brain stem and cord to sacral level spinal cord
Ascending sensory
tracts are
predominantly
situated at
tegmentum

Dorsal Column (e.g. light touch

proprioception

Spinothalamic tract
(e.g. pain, temperature)
Descending motor
tracts are
predominantly located
at the basal areas of
brain stem
“Rule of 4” of the Brainstem
(Gates, 2005) ‘A simplified method for understanding
brainstem anatomy and brainstem vascular
syndromes for the non-neurologist’.
FOUR RULES
• 4 structures in the
‘midline‘ beginning with M
• 4 structures to the ‘side’
(lateral) beginning with S
• 4 cranial nerves in the
medulla, 4 in the pons and
4 above the pons (2 in the
midbrain) Midline “Side” (Lateral)
• The 4 motor nuclei that are 1. MN, motor nucleus (3, 4, 5. SC (spinocerebellar)
in the midline are those 6 or 12);
that divide equally into 12 2. MLF (medial longitudinal 6. St (spinothalamic)
except for 1 and 2, that is 3, fasciculus)
4, 6 and 12 (5, 7, 9 and 11 3. ML (medial lemniscus) 7. Sym (sympathetic)
are in the lateral brainstem)
4. MP (motor pathway, e.g. 8. Sv (sensory nucleus
corticospinal tract) of 5th cranial nerve)

https://lifeinthefastlane.com/ccc/brainstem-rules-four/
 Blood Supply to the Brainstem
⚫ Paramedian branches
⚫ Basilar artery
⚫ Ventral / Anterior spinal artery
⚫ Long circumferential branches
(SAP)
⚫ Posterior cerebral artery
⚫ Superior cerebellar artery (SCA)
⚫ anterior inferior cerebellar
artery (AICA)
⚫ posterior inferior cerebellar
artery (PICA)

https://lifeinthefastlane.com/ccc/brainstem-rules-four/
https://dentistryandmedicine.blogspot.hk/2011/11/central-nervous-systemcns-blood-
supply.html
Blood Supply to the
Brainstem ⚫ Paramedian branches
⚫ Basilar artery
⚫ Ventral / Anterior spinal
artery

⚫ Long circumferential
branches (SAP)
⚫ Posterior cerebral artery
⚫ Superior cerebellar artery
(SCA)
ST: spinothalamic tract; ML: ⚫ anterior inferior cerebellar
medial lemniscus (ML); CP: artery (AICA)
cerebral peduncle; RN: Red
⚫ posterior inferior
nucleus; BP: basis pontis;
ON: Olivery nuclei; P:
cerebellar artery (PICA)
Pyramid; Roman numbers
indicates the cranial nerves
https://neupsykey.com/stroke-9/
 Midbrain
(Basilar)
RedNr CPT
SN
CST • Motor pathway:
CPT Cerebral peduncle
Anterior
BP
(Basis Pedunculi (BP) or
Crus Cerebri) including
Corticospinal Tract (CST)
(middle) &
Corticopontine Tract (CPT)
• Descending motor fibres
• Substantia Nigra (SN)
Red
CPT
• Produce dopamine for
Nucleus
motor control
CST

CPT
Nucleus of Oculomotor Nerve (CN III)

Midbrain
(Tegmentum)
PAG
STT
MLF ML
Medial Lemniscus (ML)
• Tactile, proprioception, vibration
sensation
Anterior Medial longitudinal fasciculus (MLF)
• Coordination of eye & head
Oculomotor Nerve (CN III) movement
- Control of external ocular muscles Motor nucleus: Cranial nerve nuclei
CN III (upper) & CN IV (lower)
Red Nucleus
• Upper limb motor reflex
Periaqueductal Gray
(Spinothalamic Tract) • Somatic and autonomic reactions to
pain, threat and emotions
“Side” Lateral Pathway
Red
Nucleus CPT • Spinothalamic Tract (STT)
• Ascending pathway for nociceptive
and thermal sensation
CST

CPT
 Midbrain
SC SC
IC IC
IC
MGN Posterior
(Tectum)
• Superior colliculus (SC)
• Reflexive eye-head
Anterior movement
• Medial to Lateral
geniculate
nucleus (LGN) of
thalamus (part of the
visual pathway)
• Inferior colliculus (IC)
• Relay from cochlear Nc
Red
Nucleus CPT to superior colliculi and
medial geniculate
CST
nucleus (MGN)
CPT
Midbrain
Myelin Stained

Front

A
B

D
 4th ventricle

Pons
Nucleus of CN VII
MLF, CN VI
STT
Nucleus
of CN VIII
ML • Basal Region
• Motor pathway
CST &CPT • Corticopontine tracts (CPT)
cerebellar → Pontine nucleus
peduncles → Pontocerebellar fibers
Anterior → Middle cerebellar peduncle
(→ Cerebellum)
• Tegmentum Region
• MLF
• Medial Lemniscus
& STT • Corticobulbar tracts
→Medial: Abducens (VI)
• → Side: Trigeminal (V) & facial (VII)
• → Vestibulocochlear (VIII) Nuc.
• Sensory (STT)
• Reticular formation
• Superior cerebellar peduncle
Pons
Nuclei of cranial nerves
(within tegmentum)
Anterior
• S: Trigeminal (V)
• M: Abducens (VI)
• S: Facial (VII)
• Vestibulocochlear (VIII)

7
* 5
8 6
* 8

*
*
Pons

A D

C
 Rostral Medulla
MLF ML
STT Basal Region
• Motor Pathway
• Pyramid containing
corticospinal tract (CST)
• Olives
• Inferior olivary Nr
• → Contralat. cerebellum
Olive when planned movement
Anterior
Pyramid is deviated
Tegmental Region
• MLF
• Medial lemniscus (ML)
separate
• Spinothalamus tract (STT)
 Rostral Medulla
MLF ML R4 Cranial Nr. Functions
STT –– VIII. Vestibular & Balance &
Cochlear Nuclei Hearing

S VII, IX, X. Solitary Taste

Nuclei (visceral
sensory)
Sym X. Vagus (dorsal Cardiac
8 10 12 motor Nr) Function
7 Olive
Anterior Sym IX, X. Nucleus muscles in
9,10
Pyramid Ambiguus pharynx,
larynx &
upper
eosophag
us
M XII. Hypoglossal Tongue
Nucleus movement
 Caudal Medulla
Gracile Nucleus / Fasciculus Gracilus
Cuneate Nucleus / Fasciculus Cuneatus
Spinal Trigeminal → Pain and temp. of face
Nucleus
Sensory decussation → Medial Lemniscus

Pyramid (Motor Pathway)

Anterior
CST – Pyramidal decussation
Rostral Medulla
A

B C

D
Caudal Medulla
C

A
B
 Cranial Nerves (Anterior View)
Mnemonics Rule of 4

“Oh,
oh, 4 CN in
oh, Above
to Pons

touch
4 CN in
and Pons
feel
very

good
velvet 4 CN in
...ah, Medulla
heaven!”

http://teachinganatomy.blogspot.hk/2013/03/Brainstem-Gross-Anatomy-of-Medulla-Pons-Midbrain.html
 Midbrain
M
M
S

Pons
M

Medulla
M
S
RULE OF FOUR:
The 4 motor nuclei that are in the MIDLINE are those that divide equally into
12 (i.e. factors of 12) except for 1 and 2, that is 3, 4, 6 and 12 (5, 7, 9 and 11
are in the lateral “SIDE” brainstem)
Reticular Formation:
Distribution
• Diagrams illustrate the
approximate positions of
the reticular formation
within the (A) midbrain,
(B) pons, and (C)
medulla as indicated by
the dotted areas.
• Larger-sized dots
represent magnocellular
(large-celled regions),
and smaller-sized dots
represent parvocellular
(small-celled regions).
PAG = periaqueductal
gray matter.

http://what-when-how.com/neuroscience/the-reticular-formation-integrative-systems-part-1/
Reticular Formation &
Functions Ventral tegmental area

• Lateral Zone ◼
• Integrates sensory and cortical input
• Produces generalized arousal
• Medial Zone ◼
• Regulate vital functions:
Cardiovascular system, respiration,
swallowing & vomiting
• Somatic motor (somatic &
autonomic) activity
• Attention
• Midline Zone ◼
• Inhibitory neurons in the dorsal
horn→ analgesia
• Raphespinal tract →enhancing
activities of interneurons and motor
neurons
• Raphe Nuclei→Drowsiness, and http://www.nature.com/sc/journal/v47/n3/fig_tab/sc20081
insomnia 05ft.html
Reticular nuclei & Neurotransmitters
1 Ventral tegmental area

• Neurotransmitter
• Chemicals that are released by 3 2
neurons to stimulate 4
neighbouring neurons or muscle
or gland cells, thus allowing
impulses to be passed from one
cell to the next throughout the
nervous system.
• Major reticular nuclei
3
1. Ventral tegmental area
➔ Dopamine
2. Pedunculopontine nucleus 3
➔ Acetylcholine
3. Raphe nuclei (midbrain & brain
stem
➔ Serotonin
4. Locus ceruleus & medial
reticular area
➔ Norepinephrine
 Reticular nuclei & Neurotransmitters
Neuro Nucleus
Neurotransmitter Nuclei
-transmitters
◼ Dopamine Ventral tegmental area
(vta) & substantia nigra
pars compacta (SNc)

◼ Acetylcholine Laterodorsal tegmental

nucleus (ldt n.) &
pedunculo
-pontine nucleus (pp n.)

◼ Serotonin Midbrain & Brainstem

Raphe n.

◼ Norepinephrine Locus ceruleus nucleus

(lc n.)

http://vanat.cvm.umn.edu/brain18/pages/neuromodulationNuclei.html
 DOPAMINE C8H11NO2(DA)

basal
ganglia

Mesolimbocortical
Pathway: ventral
Mesostriatal Pathway:
tegmental area (VTA) to
substantia nigra to
nucleus accumbens and
basal ganglia
*
cortex

1. VTA releases dopamine to nucleus accumbens and cerebral area to

increase motivation, reinforcement of behavior & decision making
2. Substantia nigra releases dopamine to caudate and putamen in the basal
ganglia circuit in motor system for motor initiation & coordination
Ventral Tegmental Area (VTA):
Dysfunction
• Amphetamines indirectly stimulate the VTA neurons
leading to heightened mood
• Cocaine acting on cells of VTA procedure euphoric
state
• Morphine inhibits inhibitory inputs to the VTA,
which in turns increasing dopamine release
• Excessive VTA activity is found (i.e. too much
dopamine secretion) in patients with schizophrenia
ACETYLCHOLINE (ACh)
Anterior
Cingulate
Gyrus

Acetyl Choline

Fornix

pedunculopontine
Hippocampus nucleus *
• In the brain: it is involved with thought, learning and memory. It is associated
with attention, and enhancement of sensory perception upon waking.
- Damage to the ACh producing area would lead to memory deficits (e.g.
Alzheimer’s disease)
• In parasympathetic nervous system: it controls the actions of skeletal and
smooth muscles.
- Damage would lead to voluntary and involuntary muscle control
 SERONONTIN C10H12N2O
(5-HT 5-hydroxtryptamine)

Midbrain Raphe
• Role in the onset of sleep
• Activity in the serotonergic projection lessens during sleep
• Disappears during rapid eye movement (REM) sleep
• Profound effects on mood
• e.g. a drug Prozac: inhibition of reuptake of serotonin
Brainstem Raphe (Periaqueductal gray - PAG)
• Some effect to Inhibit the transmission of pain information
 NOREPINEPHRINE (NE) /Norepinephrine
NORADRENALINE C8H11NO3
/ epinephrine

*
3

1. To cerebrum: arousal, direct attention; active when watchfulness is essential; it is also

associated with reward, regulation of sleep and mood
involved with fight or flight 2. To hypothalamus: along with adrenaline, regulates autonomic functions (respiratory,
visceral, cardiovascular) via hypthalamus, brain stem nuc., spina; cord
3. To spinal cord via ceruleospinal tract: non specific activation of interneurons and
motor neurons in spinal cord; inhibition of spinothalamic tract
• Patients with ADHD often need the drug prescription to help increase levels of
noradrenaline in the brain
Clinical Conditions Related to Brain Stem

• Disorders of Consciousness ***

• Medial & Lateral Brainstem Syndrome ***
• Vertical Tract signs***
• Corticobulbar Lesions (Wk 4 Lecture – Cranial Nerve)
• Facial palsy (upper or lower motor lesion)
• Four Ds: Dysphagia, Dysarthria, Diplopia, Dysmetria
• Horner’s syndrome
• Brain Stem Region Ischemia – Wallenberg’s Syndrome
• Migraine
• Schizophrenia
• Drug Addiction
Disorders of Consciousness
• Altered Consciousness
• Lesions at reticular
formation or ascending
reticular activating
system
• At hypothalamic /
thalamic activating areas
• Lock-in syndrome
• Intact consciousness
• Damage to UMN
completely prevents
voluntary movements
(might have some eye
movements in some
cases) Tony Nicklinson
https://www.youtube.com/watch?v=96kN76PfSe0
Brainstem Syndrome
• Medial (or paramedian) brainstem syndromes
• due to para-median branch occlusion
• Lateral brainstem syndromes
• due to occlusion of the circumferential branches, also
occasionally seen in unilateral vertebral occlusion
 Brainstem Syndrome
Add contralateral
facial weakness if
upper Pons or
Midbrain

Contralateral
hemiparesis
of arm and leg

Add 3rd for midbrain

Add 6th for Pons Contralateral loss
Add 12th for medulla of vibration and
proprioception Midline “Side” (Lateral)
1. MN 3, 4, 6 or 12 5. Spinocerebellar
2. MLF 6. Spinothalamic
3. ML 7. Sympathetic
4. Motor pathway 8. Sensory

Medial (or paramedian) brainstem syndromes Lateral brainstem syndromes

due to para-median branch occlusion due to occlusion of the circumferential
branches, also occasionally seen in unilateral
vertebral occlusion
Brainstem Syndrome and
Localization
• Thus a medial brainstem syndrome will consist of the 4 M’s
and the relevant motor cranial nerves,
• and a lateral brainstem syndrome will consist of the 4 S’s and
either the 9-11th cranial nerve if the lesion is in the medulla,
or the 5th, 7th and 8th cranial nerve if the lesion is in the pons.
• If there are signs of both a lateral and a medial (paramedian)
brainstem syndrome, then one needs to consider a basilar
artery problem, possibly an occlusion.
4 Medial Structures
• Motor pathway (or corticospinal tract):
contralateral weakness of the arm and leg
• Medial Lemniscus:
contralateral loss of vibration and proprioception in the arm
and leg
• Medial longitudinal fasciculus:
ipsilateral inter-nuclear ophthalmoplegia
(failure of adduction of the ipsilateral eye towards the nose
and nystagmus in the opposite eye as it looks laterally)
• Motor nucleus and nerve:
ipsilateral loss of the cranial nerve that is affected (3, 4, 6 or
12)

https://lifeinthefastlane.com/ccc/brainstem-rules-four/
4 ‘Side’ (Lateral) Structures
• Spinocerebellar pathway:
ipsilateral ataxia of the arm and leg
• Spinothalamic pathway:
contralateral alteration of pain and temperature affecting the
arm, leg and rarely the trunk
• Sensory nucleus of the 5th cranial nerve:
ipsilateral alteration of pain and temperature on the face in
the distribution of the 5th cranial nerve
(this nucleus is a long vertical structure that extends in the
lateral aspect of the pons down into the medulla)
• Sympathetic pathway:
ipsilateral Horner’s syndrome, that is partial ptosis and a small
pupil (miosis)
https://lifeinthefastlane.com/ccc/brainstem-rules-four/
Disorders in Brain Stem
• Vertical Tract signs
• Lesions inferior to caudal medulla lead to
ipsilateral loss motor (e.g. CST) and loss of
medial lemniscus function (e.g. tactile & 2
point discrimination) and contralateral loss of
nociceptive and thermal sensations
• Above-midbrain lesions lead to contralateral
loss motor (e.g. CST) or contralateral loss of
sensory functions (nociceptive and thermal
sensations, tactile & 2 point discrimination)
 Vertical Tract signs
Corticospinal Doral Column Spinothalamic
Tract -medial lemniscus Tract

Contralateral Contralateral Contralateral

Lesions superior
to caudal medulla

Lesions inferior
to caudal medulla

Ipsilateral Ipsilateral Contralateral

Brain Stem: Summary
• Anatomy of the brain stem • Reticular nuclei &
• Sensory, autonomic and neurotransmitters
motor vertical tracts travel • Ventral tegmental area
through the brain stem →Dopamine
• Convey information • Pedunculopontine nucleus
→Acetylcholine
• 1. with modification • Raphe nuclei →Serotonin
• Dorsal column (sensory) • Locus ceruleus & medical
• Parasympathetic (autonomic) reticular area →
• Cortico-bulbar, -pontine, Norepinephrine
and –reticular (motor) • Clinical relevance:
• 2. without modification • Consciousness Disorder
• Neospinothalmic (sensory) • Schizophrenia
• Sympathetic (autonomic) • Drug addiction
• Corticospinal (motor)
Thalamus
(Diencephalon)
 Location of Thalamus

Which numbers indicate the location of thalamus?

Transverse Plane: 8
Coronal Plane: 10
Thalamus
• Collection of nuclei divided
into 3 groups by
intramedullary lamina
• Anterior, medial and lateral
groups
• Lateral→ dorsal and ventral
tiers
• Additional nuclei
• Intralaminar, reticular and
midline

Lundry-Ekman et a., 2007

Functions of Thalamus
• A selective filter for cerebral cortex
• Directing attention to important
information
• Regulate the activity level of cortical
neurons
• Relay information to cerebral cortex
• Somatosensory systems (except olfactory)
(VPL & VPM)
• Visual (LG & pulvinar) and auditory (MG)
• Basal ganglion (VA)
• Cerebellum (VL)
• Association functions
• Limbic (Anterior, LD, MD): Processes
emotional and some memory functions (MG) (LG)
• Sensory integration (LP, Pulvinar)
• Non-specific functions (M, MNG,
Intralaminar, Reticular)
• Regulates consciousness, arousal and
attention
The olfactory sense is the only external sense that is not
processed by thalamus before it reaches to the cortex

http://www.edoctoronline.com/medical-atlas.asp?c=4&id=21832
 Mammillothalamic Tract,
Fornix Substantia Nigra, Ventral Pallidum
Olfactory cortex, Amygdala

Superior Colliculus,
Pretectum
Basal Ganglion

Cerebellum
Spinothalamic Tract, Medial Lemniscus
Trigeminal Lemniscus

Inferior Colliculus, Lateral Lemniscus

Optic Tract

what-when-how.com
References
• Lundy-Ekman (2013),
Fundamentals for Rehabilitation.
• Brain Stem
Philadelphia: Saunders. 4th – Chapter 14
Edition. Chapter 15

• Gates, P. (2005). The rule of 4 of • Thalamus

the brainstem: a simplified
method for understanding – Chapter 16
brainstem anatomy and
brainstem vascular syndromes for
the non-neurologist. Internal
Medicine Journal, 2005; 35: 263–
266