Why is the brainstem so important?
1) Ascending and descending tracts of the spinal cord pass through
2) Cranial nerves located here
3) Centers for regulation of respiration, cardiovascular activity, consciousness, sleep-wake cycle all here
Caudal to rostral organization of brainstem
Continuous with spinal cord caudally
Brainstem begins at foramen magnum
Medulla oblongata, pons, midbrain
Rostrally is diencephalon (thalamus)
Dorsal to ventral organization of the brainstem
Dorsally is tectum, which is the location of the superior and inferior colliculi
Cerebral aqueduct and 4th ventricle
Tegmentum covers entire brainstem (region of cranial nerve nuclei, reticular formation and chemically-identified systems)
Basis is most ventral (region of many ascending and descending tracts)
Caudal medulla
Gray matter surrounds central canal that is continuous with spinal cord
Dorsal columns of spinal cord extend to medulla and fasciculus gracilis continues to nucleus gracilis and fasciculus cuneatus continues to nucleus cuneatus
On ventral surface, have pyraminds (myelinated fibers) and anterior median fissure
Rostral medulla
Central canal expands into 4th ventricle on dorsal surface; lower apex of 4th ventricle where it narrows into central canal is the obex
Area postrema is in walls of ventricle at the obex, and this region has no normal BBB but instead monitors blood for toxins and can trigger vomiting (“vomiting center”)
Hypoglossal nucleus and dorsal motor nucleus of the vagus are most medial on floor of 4th ventricle
On ventral side of rostral medulla, have pyramids and olives (more lateral) with inferior olivary nucleus (looks like mini-brain…) that provide major input to cerebellum
Inferior cerebellar peduncles (restiform body) are dorsolateral and extend toward cerebellum
Nucleus ambiguus
Caudal Pons
Transversely oriented mass of fibers on ventral surface in basis pontis
Looks like “bridge” between cerebellar hemispheres but fibers do not connect cerebellar hemispheres, they connect pontine nuclei (within the basis pontis) to the cerebellum
Brachium pontis or middle cerebellar peduncle are large groups of fibers that enter cerebellum
Large 4th ventricle
Superior, middle and inferior cerebellar peduncles
Superior cerebellar peduncle: rostral pons, roof of 4th ventricle
Middle cerebellar peduncle: pons
Inferior cerebellar peduncle: rostral medulla, dorsolaterally
Rostral Pons
Brachium conjunctivum or superior cerebellar peduncle is at roof of 4th ventricle
4th ventricle is closing down
Caudal midbrain
4th ventricle has turned into cerebral aqueduct (aqueduct of Sylvius)
Periaqueductal gray is gray matter around cerebral aqueduct
Cerebral peduncles on ventral surface, contain large groups of (myelinated) fibers descending from cortex to brainstem and spinal cord (corticopontine and corticospinal fibers)
Inferior colliculi are auditory
Superior cerebellar peduncle crossing
Rostral midbrain
Mickey mouse with “o” for mouth!
Cerebral aqueduct
Superior colliculi are visual (not in main visual path but receive visual input in parallel with lateral geniculate nucleus of thalamus and participate in visuomotor control)
Cerebral peduncles on ventral surface, contain large groups of fibers descending from cortex to brainstem and spinal cord (corticopontine and corticospinal fibers)
Interpeduncular fossa between peduncles (oculomotor nerves emerge from interpeduncular fossa)
Substantia nigra is dorsal to axons of cerebral peduncle and divided into pars compacta (dorsal, contains DOPA neurons) and pars reticulata (ventral, contains GABA neurons); all part of basal ganglia system
Red nuclei?
Superior and inferior colliculi
Superior colliculi: visual; dorsal surface of (rostral) midbrain
Inferior colliculi: auditory; dorsal surface of (caudal) midbrain
Substantia nigra
In midbrain
Part of basal ganglia
Lots of cell bodies
Pars compacta: dorsal, contains DOPA neurons
Pars reticulata: ventral, contains GABA neurons (in ventral tegmental area (VTA))
How are brain slices usually oriented?
Dorsal down
Ventral up
Location of cranial nerve nuclei vs. nerves
Nuclei (cell bodies): located dorsally
Nerves exit ventrally or laterally
Idealized (general) view of organization of brainstem nuclei at level of medulla
Motor nuclei medial, sensory nuclei lateral lined along dorsal surface of medulla (adjacent to 4th ventricle)
Separated by sulcus limitans (just as they are in the spinal cord)
This is general plan of cranial nerve nuclei but during development some nuclei shift ventrally and pattern is disrupted
Order of cranial nerves rostrally to caudally
Ascending numerical order rostrally to caudally starting with CN III in midbrain and XII in medulla
CN III (oculomotor)
Somatic motor nucleus and visceral motor (autonomic) nucleus (Edinger-Westphal nucleus)
Motor neurons innervate all extraocular eye muscles (incl LPS) except SO4 and LR6 to move eye up and in
Motor neurons except superior rectus project to ipsilateral eye
Emerges from interpeduncular fossa of midbrain
Damage to CN III (oculumotor)
Damage to CN III causes down and out deviation of the eye due to unopposed action of superior oblique and lateral rectus
Lateral position of eye is called lateral strabismus
Patient will have diplopia (double vision)
Lose innervation of LPS which causes ptosis (drooping of eyelid)
Axons of fibers to extraocular muscles are on the inner surface of the nerve and are sensitive to vascular disease
Usually compressed between medial temporal lobe, cerebral peduncle and edge of tentorium
Edinger Westphal nucleus
Provides autonomic component of CN III
Para pre neurons that form synapses in ciliary ganglia and then postganglionic neurons innervate pupillary constrictor and ciliary muscles
Axons of neurons in E-W nucleus travel with CN III
Normal function is to provide pupillary constriction
Damage to E-W nucleus
Damage to E-W nucleus causes dilation of pupil (mydriasis) on ipsilateral side
Patient will have no pupillary light reflex (because can’t constrict pupil!)
Axons of these neurons are on the external surface of the nerve so are damaged first, sensitive to compression, so might see pupil dilation (blown pupils) as first symptom of CN III damage
Note: other eye WILL have reaction to light when light shined in contralateral eye because signal to both E-W nuclei from shining light into just one eye!
Pathway of pupillary light reflex
1) Light into one eye
2) Signal travels bilaterally to pretectum
3) Signal to E-W nucleus
4) Signal to ciliary ganglion
5) Para post to pupillary constrictor to constrict pupils
CN VI (abducens)
Innervates lateral rectus and abducts eye
Smallest and most medially located CN (out of VI, VII, VIII) that leaves the ventral surface of the brainstem along the groove between the basis pontis and medulla–just medial to medial longitudinal fasciculus (MLF)
Normally, CN VI innervates LR on same side and projects through MLF on opposite side to innervate CN III neurons for medial rectus (lateral gaze so both eyes look at the same thing)
Damage to CN VI (abducens)
Damage to CN VI will cause eye on affected side to deviate medially (medial strabismus) and have difficulty moving laterally (abduction)
Also cannot move contralateral eye medially
Together, this is lateral gaze paralysis
Usually compressed over the temporal bone
CN IV (trochlear)
Innervates superior oblique muscle on the contralateral side
Superior oblique moves eye downward and partially in (adducted)
Nerve fibers come out dorsally below inferior colliculus of midbrain and above pons??
Damage to CN IV (trochlear)
Damage to CN IV causes diplopia (vertical) and affected (contralateral) eye appears slightly elevated and has trouble moving down and adducted
Diplopia may be most noticeable when person looking down
CN XII (hypoglossal)
Innervates muscles of the tongue
Nucleus is strung out almost entire way down medulla, dorsal and near 4th ventricle?
Nerve fibers emerge from a sulcus lateral to each pyramid, between pyramid and olive
Damage to XII (hypoglossal)
Damage to CN XII causes tongue deviation to affected/weak side
Possible atrophy of the tongue (so we know this is lower motor neuron damage)
CN VII (facial)
Innervates muscles of facial expression
Nucleus in central pons, ventral?
Damage to CN VII (facial)
Damage to CN VII causes facial paralysis or weakness (generally of both upper and lower face) on ipsilateral side
Ambiguus nucleus
Motor neurons in this nucleus innervate pharynx and larynx and axons are distributed in CN IX and X
Damage to this nucleus causes difficulty swalliwing and laryngeal function (hoarseness)
Located in rostral medulla
Dorsal motor nucleus of the vagus nerve
Major parasympathetic nucleus of the brain
Contains cel bodies of para pre fibers that influence thoracic and abdominal viscera
Remember that vagus nerve has other motor and sensory fibers, but those axons have cell bodies in other nuclei (ambiguus and solitary nuclei)
Trigeminal (V) sensory nuclear complex
Responsible for reception and initial processing of tactile, proprioceptive, pain and temp information from the head –> transmission to cerebral cortex, cerebellum, reticular formation
Three sensory nuclei associated with trigeminal afferents and span rostral midbrain all the way down to upper cervical spinal cord:
1) Mesencephalic nucleus (proprioception, muscle spindle afferents; most rostral)
2) Principal sensory nucleus (fine touch; near center of column in mid pons)
3) Spinal nucleus (pain and temperature; in caudal medulla looks like dorsal horn of spinal cord; most caudal)
Spinal nucleus
Pain and temperature
Primary afferents enter through 3 divisions of trigeminal nerve (ophthalmic, maxillary, mandibular) and cell bodies located in trigeminal ganglion
Enter brainstem at level of pons then fibers enter spinal trigeminal tract just lateral to spinal trigeminal nucleus
Fibers descend and terminate on spinal trigeminal nucleus (divided into oral, interpolar and caudal regions with caudal nucleus particularly important in processing pain and temperature)
Reflexes that depend on sensory nuclei associated with trigeminal afferents
Corneal reflex: touching cornea of one eye causes bilateral blinking and closing of the eyes; depends on spinal nucleus of V pathway
Jaw reflex: tap chin and get masseter reflex; afferent limb of reflex is neuron from mesencephalic trigeminal nucleus which goes to motor nucleus of CN V, and motor neuron goes back to masseter (muscles of mastication by V3); depends on mesencephalic nucleus pathway
Main (principal) sensory nucleus
Discriminative tactile and proprioceptive sensation
Homologous to dorsal column nuclei of dorsal column-medial lemniscus tract
Many fibers from main sensory nucleus cross midline and JOIN medial lemniscus to ascend to thalamus where info can get to cortex
Mesencephalic trigeminal nucleus
Receives Ia afferents from muscle spindles in muscles of mastication and from mechanoreceptors in gums, teeth and hard palate
Afferent fibers enter brainstem through mandibular division of CN V (just like other afferents), but their cell bodies are in mesencephalic trigeminal nucleus within CNS (not trigeminal ganglia)
Some central processes end in motor and sensory nuclei of CN V but others enter cerebellum
Nucleus of the Solitary Tract (solitary nucleus)
Group of central fibers (tract) surrounded by cell bodies (nucleus)
Rostral part mediates taste sensations (VII, IX, X)
Caudal parts receive information from visceral receptors that participate in cardiovascular and respiratory reflexes (IX, X)
Auditory nuclei (VIII)–Central Pathway
Fibers of the auditory system take different routes on their way from cochlea to cerebral cortex, and cross at multiple locations
1) Primary auditory fibers in cochlea and their central processes form cochlear division of vestibulo-cochlear nerve (CN VIII)
2) Fibers enter brainstem near ponto-medullary junction and terminate in dorsal cochlear and ventral cochlear nuclei (located immediately lateral/dorsal to to inferior cerebellar peduncle in rostral medulla)
3) Fibers from cochlear nuclei cross midline to enter lateral lemniscus which projects to inferior colliculus in midbrain see steps 4-5)
4) Axons from dorsal cochlear nucleus cross midline and enter lateral lemniscus without any synapses but axons from ventral cochlear nucleus take a little longer–they project to superior olivary nuclei on either ipsilateral or contralateral side
5) Axons from ventral cochlear nucleus that went to superior olivary complex cross midline to form trapezoid body (located ventral to medial lemniscus) then join lateral lemniscus as it ascends to inferior colliculus
6) Neurons in inferior colliculus project to medial geniculate, a relay nucleus of the thalamus. The fibers form the brachium of the inferior colliculus
7) Neurons in medial geniculate project to primary auditory cortex (areas 41 and 42) which is located on superior surface of temporal lobe
Damage where causes unilateral vs. bilateral hearing loss?
Unilateral hearing loss only if damage to cochlear nuclei (dorsal or ventral)
As soon as you pass that point, will get bilateral hearing loss
Corticobulbar pathway
From cortex to brainstem (descending fibers)
Cerebral cortex gives info to motor cranial nerve nuclei
Fibers accompany corticospinal fibers within internal capsule and cerebral peduncle (basis pedunculi) and continue to brainstem nucleus that they innervate, then synapse on interneurons or motor neurons directly
Corticobulbar control
Supranuclear innervation of motor cranial nerve nuclei/corticobulbar control is primarily bilateral
No clear area of decussation
However, contralateral is often stronger
AND exception is that neurons to lower face receive innervation primarily from contralateral cortex
Damage to corticobulbar fibers to the face (within the brain) vs. damage to facial nerve or nucleus
Damage to corticobulbar fibers to the face (within the brain): weakness or paralysis of lower face only, on opposite side of lesion
Damage to facial nerve or nucleus: weakness or paralysis of entire face on same side as lesion
Symptoms if you get damage to right pyramid and medial lemniscus at the level of the rostral medulla
Left side body weakness because damaged right pyramid part of corticospinal tract
Left side loss of position sense because damaged right medial lemniscus part of dorsal column-medial lemniscus tract
Tongue deviates to right because damaged hypoglossal nerve
Reticular formation
Occupies central core of brainstem, located within brainstem tegmentum (dorsal part of brainstem)
Many aggregations of neurons within network of interlacing fibers traveling in many directions–“net-like” appearance
Cells in reticular formation give rise to long ascending and descending fibers and these cells can influence each other via collaterals
Connections in reticular formation
Convergence of many types of afferents
Receives sensory information from spinal cord, sensory cranial nerves, cerebellum, hypothalamus, basal ganglia and cerebral cortex
Efferents of reticular formation go to spinal cord, midline and intralaminar nuclei of thalamus and hypothalamus
Functions of reticular formation
Motor activity
Respiratory and cardiovascular functions
Mechanisms of sleep and consciousness
Eye movement control centers in reticular formation
Lateral gaze center generates rapid horizontal movements of the eye
Near midline of pons, near abducens nucleus in a region called paramedian pontine reticular formation (PPRF)
Receives input from cortical eye control regions in contralateral cortex (eye fields) then PPRF projects to neurons in abducens nucleus –> MLF –> medial rectus motor neurons in contralateral oculomotor nucleus; also projects to lateral rectus on ipsilateral side
Each PPRF generates lateral gaze to ipsilateral side as PPRF
Ascending reticular activating system
Maintenance of consciousness: normal cerebral cortex not capable of functioning in conscious manner unless it has input from reticular activating system of reticular formation in brainstem!
Widespread cortical activation
Areas of reticular formation that project to thalamic nuclei (midline and intralaminar nuclei) which in turn project to cerebral cortex
Midbrain-pontine reticular formation (top of pons) is primary location of this system
Motor pathways of the brainstem
These function in conjunction with corticospinal pathway to provide lots of purposeful and automatic movement patterns
Lateral pathways: lateral corticospinal tract, rubrospinal tract
Intermediate: lateral (medullary) reticulospinal
Medial pathways: medial (pontine) reticulospinal, vestibulospinal, tectospinal
General principle of what lateral vs. medial motor pathways do
Lateral pathways: flexor muscles and fine motor control, especially of upper limbs
Medial pathways: extensor muscles and postural control
Corticospinal and corticobulbar tracts
Provide most direct and specific projections from cortex to motor neurons of spinal cord and brainstem
Some fibers from cortical neurons synapse directly with motor neurons
Other neurons contact interneurons involved in various reflex pathways
Rubrospinal tract
Very close to lateral corticospinal tract
Originates in magnocellular region of red nucleus, crosses midline, descends in lateral column as rubrospinal tract (through cervical levels only)
Neurons that give rise to this pathway receive afferents from cerebral cortex (corticorubral pathway) and cerebellum
Facilitates flexors of upper limb and contributes to skilled, goal-directed movements
Reticulospinal tracts
Major alternatives to (and cooperate with) the pyramidal tract for control of motor neurons
Lateral (medullary) reticulospinal tract: facilitate voluntary motor activity and reduce strength of spinal reflexes
Medial (pontine) reticulospinal tract: facilitates extensor muscles
Lateral (medullary) reticulospinal tract
Originates in region dorsal to inferior olivary complex and descends in anterior lateral columns
Originates from bilateral regions of reticular formation, but ipsilateral projections are most numerous
May reduce strength of some spinal cord reflexes and facilitate more voluntary control of movement; when intensely activated, may produce loss of muscle tone and may be associated with decreased muscle tone that occurs during REM sleep
Medial (pontine) reticulospinal tract
Originates from pontine tegmentum and descends ipsilaterally in ventral column
Medial motor pathway
Facilitates proximal and extensor muscles
Lateral vestibulospinal tract
Originates from lateral vestibular nucleus and descends ipsilaterally in ventral column to all levels of spinal cord
Receives input from vestibular portion of CN VIII and from cerebellum
Facilitates extensor muscles of upper and lower limbs (is a medial pathway)
What does it mean to be a medial pathway?
Medial pathways help with extension, support, adjustment in posture
Cortex to brainstem to spinal cord pathways
All cortex to brainstem to spinal cord pathways have crossed by the time they reach the spinal cord even though decussation varies among pathways
So obvi motor pathways that originate from right cortex influence primarily left side of body
Lateral vestibulospinal path is an exception because receives little input directly from cortex and has ipsilateral influences
Decorticate pattern of spasticity
An upper motor neuron syndrome
Due to lesions of motor pathways above red nucleus
Decorticate pattern of spasticity is flexion of upper limbs and extension of lower limbs (antigravity muscles)
Common in lesions of internal capsule, cerebral cortex, brainstem
Decerebrate pattern of spasticity
An upper motor neuron syndrome
Massive brainstem lesion of motor pathway in brainstem below red nucleus
Decerebrate pattern of spasticity is extension of body and all limbs
Three neurotransmitter systems of the brainstem
Serotonergic
Noradrenergic
Dopaminergic
Note: the brainstem is the location of many cell bodies of neurons in these systems but their axons are widely distributed throughout the CNS and many different types of receptors allow for many different effects
Serotonergic pathways
Located in raphe nuclei that form continuous column near midline throughout brainstem tegmentum
Logical organization with more rostrally located groups projecting to forebrain and cerebellum and more caudally located groups projecting to spinal cord
Some fibers terminate in substantia gelatinosa to form part of central pain control system
Ascending fibers involved in sleep-wake cycle (neurons in raphe increased activity during wakefulness and decreased activity with onset of sleep)
Ascending fibers involved in affective behavior and may contribute to mood elevation (SSRIs used to treat depression)
Noradrenergic pathways
Neurons located in cell groups of pontine and medullary reticular formation, including locus ceruleus in pons (just rostral to facial colliculus)
Neurons have a bluish tint (locus ceruleus means blue place)
Projections very widespread, branch extensively, and affect almost every region of brain and spinal cord
Locus ceruleus plays important role in sleep-wake cycle
Release of noradrenaline increased during periods of vigilance or increased attention, and this system may enhance ability of target neurons to respond to other inputs such as those from sensory systems
Dopaminergic pathways
Neurons located in midbrain and concentrated in substantia nigra and ventral tegmental area
Two major projection systems arise:
1) Substantia nigra, pars compacta to striatum (caudate and putamen) is called nigrostriatal system; loss of dopaminergic neurons in substantia nigra found in Parkinson’s disease
2) Ventral tegmental region to septum, amygdala and frontal lobe are mesolimbic and mesocortical dopaminergic systems; overactivity in these systems hypothesized as cause of types of schizophrenia
Corneal reflex
Touch the eye and both eyelids blink
Afferent limb is the trigeminal nerve
Trigeminal afferent fibers with cell bodies in trigeminal ganglion project directly to the spinal nucleus of V
Efferent limb is facial nerve (which makes your orbicularis oculi close the eyelids on both sides)
