Clinical Neuroscience: Brainstem Neuroanatomy PDF

Clinical neuroscience - Neuroanatomy THE NEUROLOGICAL BRAINSTEM: LOCKED IN A SMALL SPACE PT.2 NUCLEI OF CRANIAL NERVES In the brainstem even minor lesions can lead to significant deficits because there is the impact of multiple structures simultaneously = Brainstem sy...

Clinical neuroscience - Neuroanatomy THE NEUROLOGICAL BRAINSTEM: LOCKED IN A SMALL SPACE PT.2 NUCLEI OF CRANIAL NERVES In the brainstem even minor lesions can lead to significant deficits because there is the impact of multiple structures simultaneously = Brainstem syndromes. 1  Clinical neuroscience - Neuroanatomy A CN deficit can be: - Central lesion (brainstem): usually involve more than one CN = multiple CN deficits. - Peripheral lesion (nerve fibers outside the brainstem) = clinical picture limited to one specific CN and its respective deficit. For example: Deficits associated to the oculomotor (problem in constricting the pupil) = lesion in the midbrain (rostral part). 2  Clinical neuroscience - Neuroanatomy Deficits of the hypoglossal nerve (protruding the tongue) = lesion in the lateral region of the medulla oblungata, in the tegmentum. Lesion of the brainstem often entail problem in ocular movements à abducens nerve, oculomotor nerve, trochlear nerve and 6 muscles: - superior rectus (upward movement), - medial rectus (inward movement), - inferior rectus (downward movement), - lateral rectus (outward movement), - inferior oblique (upward and outward movement) - superior oblique (downward and outward movement. Eye movements: elevation/depression, adduction/abduction, intorsion/extorsion. 3  Clinical neuroscience - Neuroanatomy One of the presentations of oculomotion involvement is strabismus = deviation of the eye that the patient cannot overcome à characterized by visual axes that assume a position relative to each other different from that required by the physiological conditions. The various forms of strabismus = tropias: cyclotropia, esotropia, exotropia, hypertropia and hypotropia. CRANIAL NERVES TERRITORIES Recall on the spinal cord territories: - Somatosensory territory: voluntary motor control of the skeletal muscles. Located in the ventral horn à motor neurons send axons through ventral roots. - Visceromotor territory: controls involuntary movements of internal organs and glands. Located in the lateral horn (thoracic and upper lumbar areas), involves preganglionic neurons of the ANS. - Viscerosensory territory: processes sensory info from internal organs (rreflexive control and subconscious sensations, like pain or fullness). Inputs relayed to the dorsal horn. - Somatosensory territory: sensory information from skin, muscles and joints (touch, temperature, pain, proprioception). Neurons enter through dorsal roots and can trigger reflexes action or ascend to the brain. The brainstem, however, has 7 territories not found everywhere not consistent. Territories are organized medial to lateral with the special somatic afferent (sensory) most lateral and the general somatic efferent (motor) more medial. 4  Clinical neuroscience - Neuroanatomy SPECIFIC NUCLEI OR RELAY NUCLEI Mostly found within the tegmentum (oldest part of the brainstem), except the pontine nucleus. Medulla: - Nucleus gracilis and cuneatus: dorsal column medial lemniscus pathway. - Accessory cuneate nucleus: cerebellar pathway. - Inferior olivary nucleus: motor coordination à inferior olive = several nuclei in relation with the cerebellum and different sensory and motor pathways = can be described as a relay center. Pons: - Superior olivary nucleus (interposed in the lateral lemniscus) and trapezoid body: for the acoustic pathway (localization of stimuli). - Pontine nucleus1: motor information from the cortex and neocerebellum. Neocortex sends fibers down through internal capsule to reach basilar nuclei of the pons à project contralaterally to the neocerebellum through the middle cerebellar peduncle. 1 Develop later = that’s why they are the only nuclei in the base of the brainstem, 5  Clinical neuroscience - Neuroanatomy Midbrain (in the rostral part of the tegmentum and extend in the subthalamus): - Substantia nigra: dopaminergic nucleus involved in reward mechanism, divided into pars compacta and pars reticulata. - Red nucleus: motor coordination (cortico- rubro-spinal tract). In animals divided into magnocellular portion (rubrospinal tract) and parvocellular portion (cerebellar circuits) à in humans mostly parvicellular. RETICULAR FORMATION It is made by a meshwork of widely interconnected neurons that extend from the cortex to the spinal cord, passing through the brainstem (tegmentum). It is the oldest part of the brainstem = functions vital for survival (adjustment of the internal environment in response to the external environment). It can be considered a well-organized mess (histological chaotic appearance – organized functional significance) It is made by: - parvocellular, small neurons, involved in local circuits - magnocellular long neurons, ascending and descending. The RF can be subdivided from different POV: - Cytoarchitectonic classification = based on the specific organization of cells: median (raphe) nuclei, paramedian nuclei and lateral nuclei. 6  Clinical neuroscience - Neuroanatomy - Neurochemical classification: based on NTs: Serotoninergic nuclei (raphe nuclei, close to the midline): associated with behavior problems (depression, anxiety, aggressiveness), altered pain/temperature modulation and altered motor control. Cholinergic nuclei (pons): projecting to the cerebellum and hippocampus, involved in arousal and motor system. Noradrenergic nuclei (locus coeruleus2): projects extensively à mediate modulation of pain (descending pathway), mood (projecting to higher centers), attention, sleep-wake cycle and feeding behavior. Adrenergic nuclei (medulla) Dopaminergic nuclei (substantia nigra): o Mesocortical (movement disorders) o Mesolimbic (reward, addiction) o Mesostriatal (working memory, attention). PAIN MODULATION CENTER Ascending pain pathways carry sensory pain information from the body to the brain. The central pain modulatory network can modulate these signals through descending pathways, primarily acting on the dorsal horn of the spinal cord, particularly on: - Afferent nociceptive fibers on 2nd order projecting neurons - Inhibitory interneurons. This network has either antinociceptive (during fight-or-flight responses) or pronociceptive effects (in chronic pain) via descending pathways that utilize serotonin, epinephrine or dopamine. The input is given by the periaqueductal gray matter (does not directly project neurons to the spinal cord). Central pain modulatory network: - Cingulate Gyrus = part of the limbic system, located in the medial aspect of the brain, just above the corpus callosum. 2 The locus coeruleus is a bilateral structure, situated near the fourth ventricle, in the upper part of the pons. It is the primary source of norepinephrine in the brain. It sends widespread projections throughout the brain and spinal cord. It plays an important role in stress and arousal. 7  Clinical neuroscience - Neuroanatomy - Locus Coeruleus - Dorsolateral Pontine Tegmentum = the upper lateral portion of the pons. Contains nuclei involved in autonomic functions, sleep-wake regulation, and sensory processing = connects sensory processing regions to the descending pain control systems and is involved in how the brain processes and responds to pain stimuli. It influences the perception of pain by integrating sensory input and influencing the brain's arousal state. - Rostral Ventromedial Medulla (RVM) = brainstem region involved in the descending modulation of pain. It contains two types of neurons: ON-cells (which facilitate pain) and OFF-cells (which inhibit pain). à The cingulate gyrus and locus coeruleus are involved in the emotional and arousal- related aspects of pain. à The locus coeruleus and RVM are crucial in modulating the intensity of pain signals as they travel from the spinal cord to the brain. VITAL CENTERS In the RF: - The respiratory, the swallowing and the vomit centers are located ventrally. - The cardiac, the urinary/bladder control, defecation and pneumotaxic centers are located dorsally. All of them are strongly intertwined with the ANS, through which they act on the peripheral visceral organs. Respiratory centers Several sets of nuclei (inhibitory and excitatory). They receive info from the periphery and control inspiration/expiation ensuring correct levels of pH and CO2. Some nuclei regulate inspiration, some nuclei regulate expiration and a third group is involved in rhythm generation (there is a central pattern generator3 for respiration). The 2 large groups of neurons are in the medulla (ventral and dorsal) and pons. - Medullary Respiratory Centers: Dorsal Respiratory Group (within the nucleus of the solitary tract). Primarily controls inspiration. It generates the basic rhythm of breathing by sending signals to the diaphragm and other inspiratory muscles. The DRG receives input from peripheral chemoreceptors, stretch receptors, and baroreceptors. Ventral Respiratory Group (VRG): Active during both inspiration and expiration but mainly controls forced expiration during activities like exercise. It sends signals to the expiratory muscles, such as the abdominal and intercostal muscles. - Pontine Respiratory Centers: Pneumotaxic Center (the upper part of the pons). 3 A Central Pattern Generator (CPG) is a neural circuit within the central nervous system (CNS) that can produce rhythmic, patterned outputs without requiring sensory feedback or external cues. CPGs are essential for controlling repetitive motor activities such as walking, breathing, and chewing. 8  Clinical neuroscience - Neuroanatomy Regulates the rate and pattern of breathing by inhibiting the DRG and controlling the duration of inspiration. Apneustic Center (Lower part of the pons). Promotes prolonged inspiration and deep breaths by stimulating the DRG. Its influence is usually inhibited by the pneumotaxic center to maintain a normal respiratory rhythm. Cough reflex: It is a protective reflex, cleaning the airways. The cough center is located in the medulla (nucleus tractus solitarius) within the reticular formation. - Sensory Input (Afferent Pathways): Irritant Receptors: located in the respiratory tract (especially in the larynx, trachea, and bronchi) detect irritants, foreign particles, or excessive mucus. They are sensitive to mechanical, chemical, and inflammatory stimuli. Signals from these receptors are transmitted via the vagus nerve (CN X) to the cough center in the medulla. - Motor Output (Efferent Pathways): The nucleus tractus solitarius integrates sensory data and communicates with the VRG (includes a CPG) to initiate cough. In particular, the cough center sends signals: Phrenic nerve to the diaphragm Spinal nerves to the intercostal and abdominal muscles Vagus and recurrent laryngeal nerves to the larynx This coordinated action causes: 1. Inhalation Phase: Deep breath is taken to prepare the lungs for a strong expulsion of air. 2. Compression Phase: The glottis closes, and pressure builds as the respiratory muscles contract. 9  Clinical neuroscience - Neuroanatomy 3. Expulsive Phase: The glottis opens, and air is rapidly expelled, producing the cough sound and clearing the airway. The cough center can be modulated by higher brain centers (suprapotine and subcortical), meaning conscious control can suppress or trigger coughing (e.g., coughing intentionally or suppressing a cough in public). Moreover, some individuals will cough when they are nervous or emotional. Cardiovascular centers: Mostly in the medulla (lateral part): - Nucleus tractus solitarius (NTS): receives signals from baroreceptors and chemoreceptors via CN IX and X to monitor blood pressure and blood chemistry. - Dorsal motor nucleus of the vagus and nucleus ambiguous: control parasympathetic output of the heart, reducing the heart rate/contractility. - Vasomotor area (including C1 and A1 areas4): regulates sympathetic responses, increasing HR/contractility and vascular resistance. This center integrates sensory data to maintain stable BP and circulation, adjusting autonomic outputs: - Afferent pathways: baroreceptors in the carotid sinus and aortic arch send sensory inputs to NTS. - Efferent pathways: parasympathetic and sympathetic pathways act on the heart and vessels. Urinary Bladder control centers: In the pons there are the medial pontine micturition center and a lateral pontine storage center, under control of the hypothalamus (anterior nucleus and paraventricular nucleus), the limbic system and the cingulate gyrus. These centers communicate with sympathetic and parasympathetic spinal centers and the Onuf’s nucleus (voluntary motor neurons in sacral segment of spinal cord). The Periaqueductal gray (PAG) integrates sensory and higher brain signals to coordinate bladder control processes through pontine centers. 4 C1 area: in the rostral ventrolateral medulla (RVLM) —> maintains BP by activating sympathetic vasomotor tone (projects to spinal cord). C1 neurons are adrenergic. A1 area: in the caudal ventrolateral medulla (CVLM) —> BP regulation and contribute to baroreflex. Project to hypothalamic and brainstem center, influencing vasopressin release and CV response. They provide C1 inhibition and they are catecholaminergic = modulatory role. 10  Clinical neuroscience - Neuroanatomy Micturition: - Detrusor Muscle (in the bladder wall): responsible for bladder contraction during urination, innervated by the parasympathetic fibers. When it contracts = facilitate the expulsion of urine from the bladder into the urethra. - Internal Urethral Sphincter (at the junction of the bladder and urethra): helps maintain continence by keeping the urethra closed. During micturition, when the bladder fills and the detrusor muscle contracts, the internal sphincter relaxes. Primarily innervated by sympathetic fibers. - External Urethral Sphincter (surrounds the urethra as it passes through the pelvic floor): under voluntary control, when it is contracted, it prevents urine from passing through the urethra. During micturition, the external sphincter relaxes, facilitating urine flow. It is innervated by the pudendal nerve. - Lateral pontine storage center: controls urine storage by contracting the external sphincter and inhibiting the detrusor muscle. - Medial pontine micturition center: control urine voiding by relaxing the external sphincter and contracting the detrusor muscle. Swallowing center: Swallowing can be controlled by the brainstem center but also be elicited at a cortical level. - Afferent portion: CN V, VII, IX, X, which arrives to the nucleus of the solitary tract. - Efferent portion: central pattern generator in the medulla. Phases of swallowing: - Oral phase: voluntary - Pharyngeal phase: involuntary, activation of the pharyngeal swallow reflex once the wall is stretched à pharyngeal muscles squeeze and upper esophageal sphincter opens. In the meanwhile, as protective mechanism, the epiglottis close and vocal folds come together to close the larynx à swallowing activation causes inhibition of the respiratory centers (exception: breast feeding). - Esophageal phase: involuntary, the bolus is propelled via the LES5. The swallowing central pattern generator includes: 5 Lower esophageal sphincter 11  Clinical neuroscience - Neuroanatomy - Dorsal swallowing group (DSG): in the nucleus of solitary tract and adjacent RF = contains neurons involved in triggering, shaping, timing the sequential or rhythmic pattern. - Ventral swallowing group (VSG): in the ventrolateral medulla adjacent to the nucleus ambiguous = contains switching neurons (switch command of the dorsal respiratory group to the motor neurons involved in swallowing), which distribute the swallowing drive to various pools of motor neurons. Motor neurons: - Intercostal nerves and phrenic nerves (for lungs): receives inhibitory signals during swallowing to pause respiration. - Cranial nerves (for upper airway and esophagus): activated by the swallowing centers to initiate swallowing process. à the pathway (peripheral afferent fibers, DSG neurons, VSG neurons, motor neurons) = oligosynaptic loop involved in swallowing and elementary reflexes. * A lesion in the territory where the nucleus of the Vagus nerve is located, is a problem for both respiratory center and swallowing center. These two centers are in communication as they can only occur in exclusion of the other. Vomit center: Vomit starts with anti-peristaltic movements (2-3cm/s) in the ileum, so that the content reaches the stomach in 3-5 min à voluntary movements are activated to increase intrabdominal and intrathoracic pressure + relaxation of the esophageal sphincters. Vomit centers can also be stimulated by: - triggers reaching the chemoreceptor trigger zone (CZ) via bloodstream à on the floor of the 4th ventricle, where CNS is not protected by BBB (D2 and 5HT3 receptors), - the vestibular apparatus (H1 and M1 receptors), from the inner ear - higher cortical centers. - Limbic system: fear and anxiety. Sensory information travels via CN X and sympathetic afferent fibers from the GI. The vomiting center is located bilaterally in the medulla, near the nucleus of solitary tract. Motor information from the centers travel via CN V, VII, IX, X and XII + spinal nerves controlling the diaphragm and abdominal muscles. Gag reflex = protective mechanism that starts with the stimulation of posterior pharyngeal wall, sensed by the IX (afferent) à reaches the nucleus of solitary tract and nucleus ambiguous à innervation of muscles of branchiomeric origin (efferent) via vagus nerve. 12  Clinical neuroscience - Neuroanatomy *While in the spinal cord there could be a monosynaptic reflex, all the reflexes of the CN have interposition of the RF. Hiccup = sudden onset of erratic diaphragmatic and intercostal muscles of contraction, followed by laryngeal closure. Might be due to stimulation of peritoneum, ear and nose, pharynx, esophagus, stomach. - Afferent: vagus and phrenic nerve à hiccup centers (nucleus of solitary tract, nucleus ambiguous and dorsal nucleus of the vagus + cervical cord C3-C5) - Efferent: activation of the respiratory muscles through sympathetic fibers (T6-T12). It is a common first symptom of lung cancer à vicinity of the phrenic nerve. Control of appetite and satiety - CCKNTS Neurons: express Cholecystokinin (CCK), located in the nucleus of the solitary tract (NST) à critical role in the regulation of feeding behavior. CCK = a hormone released primarily in the small intestine during digestion = a key satiety signal. When CCK is release, activated CCK neurons, which relay fullness signal to other areas of the brain. - PVH (Paraventricular Nucleus of the Hypothalamus): crucial brain area involved in controlling satiety and energy balance. The CCKNTS neurons send signals to the PVH, influencing feeding behavior. 13  Clinical neuroscience - Neuroanatomy - MC4RPVH: Melanocortin 4 receptor expressing neurons in the PVH à regulate appetite further and are activated by the projections from the CCKNTS neurons. Thermoregulation Temperature is under the control of neurons in the hypothalamus (preoptic area) and RF (parabrachial nucleus). They mediate pathways affecting vascular smooth muscles, activities of skeletal muscles and brown adipose tissue. - Ascending neural pathways: sensory input from the periphery. Temperature receptors in the skin detect changes in temperature à send signals via sensory nerves to the spinal cord à brainstem (parabrachial nucleus) à hypothalamus (preoptic area). Warm-sensitive and cold-sensitive neurons in the preoptic area process signals and trigger responses. - Descending pathways: control thermoregulatory effectors. Preoptic areas send signals down to activate thermoregulatory effectors to adjust body temperature = vasodilation/vasoconstriction, shivering, non-shivering thermogenesis of the brown adipose tissue, sweating Eye movements: The medial longitudinal fasciculus6 = important neural tact within the brainstem = coordinating eye and head movements. It extends longitudinally through the midline of the brainstem and into the cervical spinal cord. - Coordination of eye movements: MLF connects 6 nuclei (III, IV, VI, innervating extraocular muscles, with vestibular nuclei) = coordination of horizontal gaze (rapid and coordinated movements of both eyes in the same direction. - Vestibulo-ocular reflex (VOR): MFL stabilize the gaze during head movements by producing eye movements in the opposite direction. - Interaction with the vestibular system: integration of head movements and positional information. Eye reflexes: Pupillary reflex = consensual reflex, important to protect the retina à regulates the amount of light that comes to the retina. Inside the orbital cavity there is the parasympathetic ciliary ganglion à from it the short ciliary nerve originates, which brings: - parasympathetic postganglionic fibers = pupillary light reflex 6 It is a paired white matter tract passing close to the midline (having both ascending fibers and descending fibers), through the brainstem lying ventral to the cerebral aqueduct in the midbrain and the fourth ventricle in the pons and medulla. 14  Clinical neuroscience - Neuroanatomy - sympathetic postganglionic fibers = pupil dilation - sensory fibers from ophthalmic branch of the V). The size of the pupil is determined by a balance between sympathetic and parasympathetic: - When parasympathetic prevails = circular muscles contract = reduction of the size of the pupil. - When the sympathetic prevails = radial muscles contract = pupil dilation. Shining light on the retina à excites retinal cells, which transmit through the optic nerve to the pretectal nuclei in the midbrain. At this level the information is sent on both sides via the posterior commissure = consensual reflex. The preganglionic parasympathetic fibers originate from the Edinger-Westphal nucleus (pretectal area, close to posterior commissure) bilaterally. Fibers enter the orbital cavity where they synapse in the ciliary ganglion and reach the circular constrictor pupillae through the short ciliary nerve. The sympathetic preganglionic centers are in the spinal cord. The information of the amount of light is carried by the optic nerve to the hypothalamus: through the RF the information reaches C1-T2 segments of the spinal cord. These fibers exit the spinal cord, reach the paravertebral chain through white rami, communicates and arrive in the cervical ganglia, from where postganglionic fibers originate. From there they enter the skull and reach the eye (dilator of the pupil) = hypothalamic-spinal descending tract. These postganglionic sympathetic fibers also innervate a layer of SM called superior tarsal muscle, at the level of the eye lid. Damage to different components result in different pupil presentations: 15  Clinical neuroscience - Neuroanatomy The corneal reflex = when the cornea is damaged by external stimuli. Afferent component = ophthalmic branch of the V, whose body are in the ganglion of Gasser, that synapse on 2nd order sensory neurons in the spinal nucleus of the V. Through RF, fibers reach the motor nucleus of the VII, that innervates the orbicularis nerve, that induces blinking. Oculocephalic reflex (doll’s eyes): eyes move side to side when head is turned à when brainstem is depressed, the eyes remain fixed. Oculo-vestibular reflex (Caloric text reflex): eyes deviate to side of cold-water ear irrigation and to the opposite side with respect to warm water irrigation. In these reflexes the paramedial pontine reticular formation is involved. The abducens nerve and oculomotor nerve are the efferent fibers. Eye movements: Gaze centers are located rostrally in the midbrain: - Horizontal gaze is controlled by the pontine reticular formation. - Vertical gaze is controlled by: Rostral interstitial nucleus of the medial longitudinal funiculus (containing burst cells) Interstitial nucleus of Cajal (rostral midbrain) forming the neural integrator for maintenance of position in the orbit These regions project bilaterally, partly via the posterior commissure. Internuclear ophthalmoplegia: = impaired conjugate eye movements caused by a lesion of the MLF. The MFL is the final common pathway for different types of conjugate movements (saccades, smooth pursuit, vestibulocochlear reflex, communication with ocular motor nuclei). In fact, it connects: - VI CN nucleus - Adjacent horizontal gaze center (paramedian pontine reticular formation) - Contralateral III CN nucleus - Vestibular nuclei with III and IV CN nuclei 16  Clinical neuroscience - Neuroanatomy Ophthalmoplegia causes: - 1/3 is caused by infarctions = unilateral, seen in older individuals. - 1/3 are caused by demyelinating disorders (MS), mostly bilateral. Orofacial movements: The brainstem contains key neural circuits that drive and coordinate different cranial motoneurons to produce various orofacial actions (sniffing, chewing, swallowing, vocalizing) à which have to be all coordinated with breathing (without fatal blockages of the airway). They are controlled by the CNS and PNS + their coordination is controlled via the lateral pontine and medullary areas (regions lateral to hypoglossal/ambiguous nuclei to area surrounding facial nucleus up to trigeminal nucleus). - Chewing: neurons are adjacent to trigeminal motor nucleus - Lip movements: neurons are near facial motor nucleus - Tongue movements: neurons are near hypoglossal motor nucleus - Emotional facial expression (smile, cry): involuntary neurons are near facial motor nucleus. These neurons are under the control of higher centers that deal also with emotions. Muscle tone and movement control: postural adjustments. Consciousness: lesion in rostral brainstem can lead to its alteration: - Connection to the cortex via intralaminar nuclei of the thalamus, basal forebrain and hypothalamus, the RF is involved in alertness, awareness and attention = 3 components of consciousness. - Receiving stimuli from the ARAS (ascending reticular activating system) sends tonic stimuli to the cortex for maintenance of conscious state. 17