T HE CENTRAL NERVOUS S YSTEM P RE L ABORATORY R EVIEW OF THE B RAIN The cerebrum is the largest and considered the most recently developed area of the brain in human evolution. The cerebral hemispheres make up the superior portion of the brain. The hemispheres contain characteristic ridges called gyri (plural for gyrus) separated by shallow grooves called sulci. The deeper sulci are called fissures. They increase the surface area of the brain tissue that can fit within the cranium. The longitudinal fissure can be visualized from a superior view of the cerebrum. It divides the cerebrum into a right and left hemisphere. Each hemisphere can be further divided into 4 major lobes: the frontal, temporal, parietal, and occipital lobes. The insula is often referred to as the fifth lobe of the brain. It is not visible externally because it is buried deep within the temporal and frontal lobes. The insula has several important roles including awareness of internal bodily functions, such as the perception of having a full bladder. It also plays a role in basic emotions such as anger, happiness, fear, and disgust. The frontal lobes control voluntary motor functions, planning, mood, smell, and social judgment. The parietal lobes receive and integrate sensory information. The occipital lobes are considered the visual center of the brain. The temporal lobes are important for learning, hearing, memory, and emotional behavior. The central sulcus divides the hemispheres of the brain into anterior and posterior halves. The central sulcus is bordered by the precentral gyus anteriorly and postcentral gyrus posteriorly. The four primary lobes of the cerebrum have both characteristic and predictable functions. Structures anterior to the central sulcus are mostly related to either cognitive or motor functions. The prefrontal cortex is the anterior portion of the frontal lobes (Figure 9.4). It allows humans to solve complex problems. It is the most evolved part of the brain; its roles include higher thought processes such as judgment, working memory, personality, and abstract thinking. It is closely linked to the limbic system, which plays a major role in emotions and involuntary responses to them. The primary motor cortex is located on the precentral gyrus. Neurons in this area of the brain control voluntary skeletal muscles needed for movement. Different areas along this gyrus control different areas of the body. Broca’s area is the portion of the frontal lobe that controls the muscles that are needed for speech production. This includes muscles of the tongue and pharynx. The olfactory association area is one of the few sensory areas of the cortex that is located in the front of the brain. The olfactory cranial nerve has receptors that give the ability to distinguish many different scents. It projects to the olfactory association area, which provides associations with specific smells. The smell of homemade apple pie might remind a person of their childhood because their grandmother used to make it for them when they were young. Structures that are posterior to the central sulcus are sensory in nature. The primary sensory cortex is located on the postcentral gyrus. Like the primary motor cortex, the primary sensory cortex is also a topographical map of the body. This means specific areas along both the precentral and postcentral gyrus are dedicated to either motor or sensory functions of a specific body part. This concept will be covered in greater detail in the next laboratory. The primary visual cortex is located in the occipital lobe of the brain. The images created by the retina of the eyes will ultimately project to this area of the brain. The primary visual cortex and its neighboring associative visual cortex will give meaning to the images. Notice the enormous amount of cortex devoted to vision. The sensory association cortex is located in the parietal lobes just posterior to the primary sensory cortex and anterior to the visual association areas. This area is responsible for the blending of the senses allowing humans to recognize specific objects such as cars, people, and words. Without this area of the brain the world would be perceived as basic shapes, colors, and pitches. Past events will influence how an object is perceived. For example, when people think of the Mister Softee Ice Cream truck, they can develop a picture of it from their visual association area. Because of life experience, they can also remember the famous song that the truck plays. The visual memory of the truck and its song will always be associated with each other. If a person never saw or heard this ice cream truck before, it would not have the same meaning. The primary auditory cortex is located on the superior gyrus of the temporal lobe. Sensory impulses from the cochleae are topographically mapped here allowing for the interpretation of sound. The auditory association area functions in perception and emotional response to sound. Wernicke’s area is located posterior to the primary auditory cortex. It is particularly important in word recognition and understanding language. Clinical application: Damage to specific areas of the brain will result in predictable functional deficits. The left side of the cortex is the location of both Broca’s and Wernicke’s areas in 97% of the population. If Broca’s area was affected, the result would be an inability to vocalize speech. This is a condition called expressive aphasia. If Wernicke’s area was injured, the result would be an inability to comprehend speech (language). This is called receptive aphasia. If both areas were damaged, the person would have difficulty with both speaking and understanding the words they are listening to. This is called global aphasia. C ROSS S ECTION OF THE B RAIN AND R EGIONAL A NATOMY Viewing the sagittal section of the brain is important for studying internal structures (Figure 9.4). The corpus callosum is located in the midline just inferior to the cerebrum. It is a thick, white collection of bidirectional myelinated fibers that allow the two hemispheres to communicate. The pineal gland is located inferior and posterior to the corpus callosum. It produces melatonin, which signals the body to sleep. The thalamus is superior to the hypothalamus. The thalamus plays a major role in relaying sensory and motor signals to and from the cortex. The hypothalamus regulates many basic functions such as body temperature, thirst, hunger, sleep, and hormone production. The hypothalamus also has specific nuclei for the autonomic nervous system. The autonomic nervous system is important in regulating many basic involuntary functions such as digestion and dealing with stress. The pituitary gland is a small, pea-shaped gland that is located within a depression in the sphenoid bone called the sella turcica described earlier in the skull exercise. It is directly connected to the hypothalamus. It is often referred to as the master gland because it secretes many hormones. Hormones act as chemical messengers that play a role in regulating homeostasis of many bodily functions such as body temperature, blood pressure, growth and development, reproduction, electrolyte balance, and water regulation. All of the pituitary’s actions are governed by the hypothalamus. The brainstem consists of the midbrain, pons, and medulla oblongata. The midbrain contains specific nuclei important for arousal because of its connection with the reticular activating system (RAS). It produces dopamine, which is an important neurotransmitter for movement control. The pons functions as a bridge from the cortex to the cerebellum. Additional functions of the pons are related to posture, sleep, hearing, balance, taste, eye movements, facial expression, facial sensation, and respiration. This is because many of the cranial nerves that control the above functions originate here. The medulla oblongata contains specific nuclei that control cardiac functions. When stimulated by the sympathetic nervous system, the medulla triggers neurons that increase blood pressure, heart rate, and increase the heart muscle’s force of contraction. It can also decrease heart rate and force of contraction when stimulated by the parasympathetic nervous system. The medulla also has nuclei that form the primary respiratory centers. These control both the rate and depth of breathing. The spinal cord is just inferior to the medulla oblongata. The spinal cord functions as a collection of ascending and descending neuronal tracts that allows the brain and the body to communicate. The spinal cord’s functions will be covered in greater detail later in this laboratory. The cerebellum (Greek translation: “little brain”) is the large round structure posterior to the brainstem. The gray and white matter resembles a leaf (arbor vitae, Greek translation: “tree of life”). This area integrates input from various areas of the brain and spinal cord. This integration is critical for the timing of learned movements. In short, it is critical for balance and coordination. The autonomic nervous system (ANS) is a subdivision of the peripheral nervous system. The ANS regulates the function of internal organs (viscera). These include involuntary functions, such as the regulation of blood pressure, bowel, and bladder functions. The ANS can be divided into two major divisions. The sympathetic nervous system (SNS) is responsible for the fight-or-flight reaction in response to stress. When the SNS is activated due to an external or internal stressor, the body will down-regulate functions relating to maintenance and repair, such as the digestive and urinary systems. Blood will be preferentially shunted away from the organs of the gut toward the larger muscle groups, heart, and brain. The parasympathetic nervous system (PNS), aka cranial sacral system, is important for all things associated with recovery and restoration such as resting and digesting food. It enhances the enteric nervous system, whose primary role is digestion. The PNS influences the SNS to shift the body’s blood away from skeletal muscles toward the mesenteric vessels, which supply the intestines and allow for absorption of nutrients for digestion. Blood flow to the kidneys is also increased, which is necessary for blood filtration and formation of urine. S PINAL C ORD AND M ENINGES R EVIEW The spinal cord extends off of the brainstem and exits from the cranial cavity via the foramen magnum at the base of the occipital bone. The spinal cord’s primary function is to communicate information in the form of impulses to and from the brain. Ascending tracts send information from peripheral nerves to the brain, allowing for sensory perception. The brain controls various bodily functions through impulses sent down descending tracts. Descending tracts target muscles, glands, and organs. The tracts will be covered in greater detail in future labs. Find the vertebral foramen (spinal canal). Recall from a previous lab that this was the opening within the vertebra for the spinal cord. Observe the model and orient yourself to the anterior and posterior side. Name an anatomical structure of the vertebra that would be found anterior to the spinal cord. ______________________________________ Posterior: ______________________________________ Identify the epidural space. This is the outermost layer of the spinal canal. This area contains fatty tissue, blood vessels, and lymphatic vessels. Moving centrally, identify the three meningeal layers (dura mater, arachnoid mater, and pia mater). The outermost meningeal layer (dura mater) is located just deep to the epidural space and is continuous with the epineurium of the peripheral nerves. The middle meningeal layer (arachnoid mater) creates the outermost border of the subarachnoid space, which is located between the pia and arachnoid layers. The cerebrospinal fluid circulates within this space. Locate the pia mater, which is in direct contact with the spinal cord. The cross section of the spinal cord reveals two distinct regions. The gray matter is a butterfly-shaped structure in the center of the spinal cord. The outer white matter is composed of the various ascending and descending tracts (myelinated axons) of the spinal cord. The gray matter has both a posterior (dorsal) horn and an anterior (ventral) horn bilaterally. Sensory neurons enter to the dorsal horn via the dorsal roots of the peripheral nerves. Follow the dorsal roots laterally and identify the dorsal root ganglion. This area of enlargement contains the cell bodies of the sensory neurons. Motor neurons originate in the ventral horns of the spinal cord. They exit via ventral roots before they combine with the dorsal roots to form a spinal nerve. The spinal nerve projects to their target organs, glands, or muscles. Interneurons are small neurons located in the gray matter. These neurons are important for coordinating opposing muscle groups. Clinical application: An epidural nerve block is a medical procedure in which a needle is inserted into the epidural space to deliver medication to reduce inflammation around a nerve or block the transmission of pain. Lumbar punctures are a medical procedure in which a needle is introduced into the subarachnoid space to remove cerebral spinal fluid. This is done to look for the presence of bacterial infections and diagnosing diseases that affect the central nervous system, such as multiple sclerosis. The brain and spinal cord are covered by three layers collectively known as the meninges (dura mater, arachnoid mater, and pia mater) (Figure 9.1). The dura mater (Greek translation: tough mother) is the outermost meningeal layer that protects both the brain and spinal cord. This layer lines the cranial cavity and the inside of the vertebral foramen. Cranial dura mater contains various sinuses which are important structures that collect venous blood from the brain and eliminate excessive cerebral spinal fluid from its circulation. The middle meningeal layer is the arachnoid mater, named because it resembles a spider web. It is a thin, transparent membrane that cushions the central nervous system. The pia mater is located just beneath this layer. It is in direct contact with the outer cortex. The subarachnoid space is located between the pia and arachnoid layers. It contains the cerebral blood vessels and circulating cerebrospinal fluid. This fluid-filled space protects the brain and spinal cord from trauma and is necessary for regulating cerebral functions such as blood flow distribution, nutrient and waste product regulation. The choroid plexus in the brain’s ventricles contributes to some of the cerebral spinal fluid production. The cerebral cortex contains the brain’s gray matter. This area of the brain is composed mostly of neuronal dendrites, cell bodies, and synapses. Cortical impulses such as voluntary movement originate from the cortex, while sensory perception will terminate here. The white matter represents the axons of the neurons. The white appearance is due to the presence of myelin. Clinical application: Meningitis (inflammation of the meninges) can be a lifethreatening problem. It is often a viral or bacterial infection. The inflammation can put a tremendous amount of pressure on both the brain and spinal cord. The most common symptoms include headache, neck stiffness, fever, and altered consciousness. There are also several types of bleeding injuries that can occur involving the meninges. A subdural hemorrhage is a bleed that accumulates underneath the dura mater. Important veins can be damaged resulting in a slow bleed. This may account for the gradual onset of symptoms. Both epidural bleeds (blood accumulating between the dura mater and the skull) and subarachnoid bleeds (blood accumulating within the subarachnoid space) are arterial in nature. The arterial system blood pressure is much higher resulting in greater blood loss following injury to these vessels. A person would experience symptoms such as a severe headache and rapid loss of consciousness, which would occur almost immediately. S PINAL C ORD AND M ENINGES R EVIEW The spinal cord extends off of the brainstem and exits from the cranial cavity via the foramen magnum at the base of the occipital bone. The spinal cord’s primary function is to communicate information in the form of impulses to and from the brain. Ascending tracts send information from peripheral nerves to the brain, allowing for sensory perception. The brain controls various bodily functions through impulses sent down descending tracts. Descending tracts target muscles, glands, and organs. The tracts will be covered in greater detail in future labs. Find the vertebral foramen (spinal canal). Recall from a previous lab that this was the opening within the vertebra for the spinal cord. Observe the model and orient yourself to the anterior and posterior side. Name an anatomical structure of the vertebra that would be found anterior to the spinal cord. ______________________________________ Posterior: ______________________________________ Identify the epidural space. This is the outermost layer of the spinal canal. This area contains fatty tissue, blood vessels, and lymphatic vessels. Moving centrally, identify the three meningeal layers (dura mater, arachnoid mater, and pia mater). The outermost meningeal layer (dura mater) is located just deep to the epidural space and is continuous with the epineurium of the peripheral nerves. The middle meningeal layer (arachnoid mater) creates the outermost border of the subarachnoid space, which is located between the pia and arachnoid layers. The cerebrospinal fluid circulates within this space. Locate the pia mater, which is in direct contact with the spinal cord. The cross section of the spinal cord reveals two distinct regions. The gray matter is a butterfly-shaped structure in the center of the spinal cord. The outer white matter is composed of the various ascending and descending tracts (myelinated axons) of the spinal cord. The gray matter has both a posterior (dorsal) horn and an anterior (ventral) horn bilaterally. Sensory neurons enter to the dorsal horn via the dorsal roots of the peripheral nerves. Follow the dorsal roots laterally and identify the dorsal root ganglion. This area of enlargement contains the cell bodies of the sensory neurons. Motor neurons originate in the ventral horns of the spinal cord. They exit via ventral roots before they combine with the dorsal roots to form a spinal nerve. The spinal nerve projects to their target organs, glands, or muscles. Interneurons are small neurons located in the gray matter. These neurons are important for coordinating opposing muscle groups. Clinical application: An epidural nerve block is a medical procedure in which a needle is inserted into the epidural space to deliver medication to reduce inflammation around a nerve or block the transmission of pain. Lumbar punctures are a medical procedure in which a needle is introduced into the subarachnoid space to remove cerebral spinal fluid. This is done to look for the presence of bacterial infections and diagnosing diseases that affect the central nervous system, such as multiple sclerosis. The brain and spinal cord are covered by three layers collectively known as the meninges (dura mater, arachnoid mater, and pia mater) (Figure 9.1). The dura mater (Greek translation: tough mother) is the outermost meningeal layer that protects both the brain and spinal cord. This layer lines the cranial cavity and the inside of the vertebral foramen. Cranial dura mater contains various sinuses which are important structures that collect venous blood from the brain and eliminate excessive cerebral spinal fluid from its circulation. The middle meningeal layer is the arachnoid mater, named because it resembles a spider web. It is a thin, transparent membrane that cushions the central nervous system. The pia mater is located just beneath this layer. It is in direct contact with the outer cortex. The subarachnoid space is located between the pia and arachnoid layers. It contains the cerebral blood vessels and circulating cerebrospinal fluid. This fluid-filled space protects the brain and spinal cord from trauma and is necessary for regulating cerebral functions such as blood flow distribution, nutrient and waste product regulation. The choroid plexus in the brain’s ventricles contributes to some of the cerebral spinal fluid production. The cerebral cortex contains the brain’s gray matter. This area of the brain is composed mostly of neuronal dendrites, cell bodies, and synapses. Cortical impulses such as voluntary movement originate from the cortex, while sensory perception will terminate here. The white matter represents the axons of the neurons. The white appearance is due to the presence of myelin. Clinical application: Meningitis (inflammation of the meninges) can be a lifethreatening problem. It is often a viral or bacterial infection. The inflammation can put a tremendous amount of pressure on both the brain and spinal cord. The most common symptoms include headache, neck stiffness, fever, and altered consciousness. There are also several types of bleeding injuries that can occur involving the meninges. A subdural hemorrhage is a bleed that accumulates underneath the dura mater. Important veins can be damaged resulting in a slow bleed. This may account for the gradual onset of symptoms. Both epidural bleeds (blood accumulating between the dura mater and the skull) and subarachnoid bleeds (blood accumulating within the subarachnoid space) are arterial in nature. The arterial system blood pressure is much higher resulting in greater blood loss following injury to these vessels. A person would experience symptoms such as a severe headache and rapid loss of consciousness, which would occur almost immediately. C RANIAL N ERVES The cranial nerves are considered part of the peripheral nervous system. They control a variety of motor and sensory functions of the head and neck (Figure 9.6). These include hearing, vision, facial sensation, muscles of mastication, and facial expression. They also control numerous autonomic functions including the regulation of digestion, blood pressure, heart rate, and urinary functions. Unlike nerves projecting from upper cortical areas that control the opposite side of the body, cranial nerves innervate the same side that they originate from. Refer to your textbook for a more detailed description of the function of the cranial nerves. Clinical application: It is critical for health care providers to familiarize themselves with the 12 cranial nerves’ general functions. Health care practitioners such as EMT first responders will test these cranial nerves because it gives them important insight to a person’s current neurological status. Recall that most of the cranial nerves are originating off the brainstem and exit the base of the skull through the various foramina. Any trauma to the skull could cause an intracranial bleed. The bleed would put pressure on the brain, compressing the cranial nerves in the base of the skull. When nerves are compressed they can’t conduct their action potentials. This might present as either paralysis or loss of sensation to innervated areas. In short, any condition that puts pressure on the brain (i.e., stroke, tumor, or bleed) will affect the cranial nerves. It is important for a practitioner to understand the origins of the various cranial nerves. If a specific cranial nerve is dysfunctional this gives insight to where pressure is originating. Watch the Following videos and answer the following questions. Acland Videos: • 4.7.1 Brain: initial overview (0:44) • 4.7.9 Cerebrum (4:00) 1. Which parts of the brain occupy the posterior cranial fossa? __________________________________________________________________________ __________________________________________________________________________ __________________________________________________________________________ __________________________________________________________________________ 2. The falx cerebre contains which anatomical structure? __________________________________________________________________________ __________________________________________________________________________ __________________________________________________________________________ __________________________________________________________________________ 3. What are the 3 layers of the meninges? Describe their relationship to each other. __________________________________________________________________________ __________________________________________________________________________ __________________________________________________________________________ __________________________________________________________________________ 4. Name a major artery lining the outside of the dura mater. __________________________________________________________________________ __________________________________________________________________________ __________________________________________________________________________ __________________________________________________________________________ Acland Videos: • • • • 4.7.6 Medulla, fourth ventricle (4:48) 4.7.7 Midbrain, cerebral peduncles (2:33) 4.7.8 Cerebellum (1:41) 4.7.10 Lateral and third ventricles, underside of the cerebrum (4:02) 4.7.11 Review of brainstem, cerebellum, cerebrum (2:29) 1. What are the main ventricles of the brain? __________________________________________________________________________ __________________________________________________________________________ __________________________________________________________________________ __________________________________________________________________________ 2. Which anatomical structures make up the brainstem? __________________________________________________________________________ __________________________________________________________________________ __________________________________________________________________________ __________________________________________________________________________ 3. Which part of the brain is superior to the pons? __________________________________________________________________________ __________________________________________________________________________ __________________________________________________________________________ __________________________________________________________________________ 4. What are the main functions of the cerebellum? __________________________________________________________________________ __________________________________________________________________________ __________________________________________________________________________ __________________________________________________________________________ 5. Which anatomical structure connects the 2 cerebral hemispheres? __________________________________________________________________________ __________________________________________________________________________ __________________________________________________________________________ __________________________________________________________________________ 6. What does the lateral sulcus separate? __________________________________________________________________________ __________________________________________________________________________ __________________________________________________________________________ __________________________________________________________________________ 7. What does the central sulcus separate? __________________________________________________________________________ __________________________________________________________________________ __________________________________________________________________________ __________________________________________________________________________ A NATOMY OF THE MENINGES AND S PINAL C ORD • • • • • 4.7.2 4.7.3 4.7.4 4.7.5 3.1.8 Lining of cranial cavity, falx, tentorium (3:02) The meningeal layers: dura, arachnoid, pia (3:45) Lining of middle cranial fossa (0:53) Review of cranial cavity and meninges (1:31) Spinal cord (cross section), spinal meninges, dural sac (3:11) 3.1.9 Spinal cord (from behind), nerve roots (4:22) 1. What level does the spinal cord terminate? __________________________________________________________________________ __________________________________________________________________________ 2. Describe the difference between the dorsal and ventral roots. __________________________________________________________________________ __________________________________________________________________________ __________________________________________________________________________ 3. The nerve roots exit the vertebral canal through which anatomical structure? __________________________________________________________________________ __________________________________________________________________________ __________________________________________________________________________ 4. What is the difference between the posterior and anterior primary ramus? __________________________________________________________________________ __________________________________________________________________________ __________________________________________________________________________ __________________________________________________________________________ __________________________________________________________________________ __________________________________________________________________________ 5. How are cervical vertebra named? How does this change in the thoracic region. (why) __________________________________________________________________________ __________________________________________________________________________ __________________________________________________________________________ __________________________________________________________________________ __________________________________________________________________________ The Nerves of the Head and Neck • 4.8.9 Review of first six cranial nerves (1:40) • 4.8.11 The last four cranial nerves (cranial nerves IX, X, XI, XII) in the cranium (2:50) • 4.8.14 Sympathetic trunk, cervical plexus (2:27) • 4.8.15 Review of last six cranial nerves (1:28) 1. List the 12 cranial nerves and describe their general functions. __________________________________________________________________________ __________________________________________________________________________ __________________________________________________________________________ __________________________________________________________________________ __________________________________________________________________________ __________________________________________________________________________ __________________________________________________________________________ __________________________________________________________________________ __________________________________________________________________________ __________________________________________________________________________ __________________________________________________________________________ __________________________________________________________________________ __________________________________________________________________________ __________________________________________________________________________ __________________________________________________________________________ __________________________________________________________________________ K EY S TRUCTURES OF THE B RAIN A ND S PINAL C ORD Central Nervous System Anatomy Cerebral Cortex/Autonomic Terms Inner/Inferior Brain Structures Meninges Frontal lobe Pineal gland • Dura mater • Olfactory association area Brainstem • Arachnoid mater • Prefrontal cortex • Midbrain • Subarachnoid space • Primary motor cortex • Pia mater • Precentral gyrus • Reticular Activating System (RAS) Choroid plexus Cerebrum • Gray matter • Sulci • Broca’s area • Pons Insula • Medulla oblongata Parietal lobe Thalamus • Central sulcus • Primary sensory cortex • Fissures • Postcentral gyrus • Longitudinal fissure • White matter Epidural space Spinal cord • Dorsal horn • Ventral horn • Dorsal root • Ventral roots Hypothalamus Pituitary gland Cerebellum Occipital lobe • Arbor vitae • Primary visual cortex Cranial nerves Temporal lobe • Olfactory (I) • Primary auditory cortex • Optic (II) • Wernicke’s area • Auditory association area • Oculomotor (III) • Trochlear (IV) • Trigeminal (V) • Abducens (VI) • Facial (VII) • Vestibulocochlear (VIII) • Glossopharyngeal (IX) • Vagus (X) • Spinal Accessory (XI) • Hypoglossal (XII) CLINICAL CASE STUDIES 1. Critical thinking question: A person is admitted to the hospital with complaints of a severe headache and double vision. An X-ray revealed a mass within the sella turcica. What structure sits within this area? _________________________________________________________________ _________________________________________________________________ Examine both the brain and cranial fossa anatomy to explain this person’s symptomology. _________________________________________________________________ _________________________________________________________________ _________________________________________________________________ _________________________________________________________________ _________________________________________________________________ _________________________________________________________________ _________________________________________________________________ _________________________________________________________________ _________________________________________________________________ _________________________________________________________________ _________________________________________________________________ _________________________________________________________________ _________________________________________________________________ _________________________________________________________________ 2. A patient is admitted to the hospital with a traumatic brain injury. He is conscious, but has paralysis on the left side of his face. He also has difficulty standing on 1 foot with constant ringing in his ears. What cranial nerves may have been involved in the injury? (Explain.) ______________________________ _________________________________________________________________ _________________________________________________________________ _________________________________________________________________ _________________________________________________________________ _________________________________________________________________ _________________________________________________________________ _________________________________________________________________ _________________________________________________________________ _________________________________________________________________ _________________________________________________________________ _________________________________________________________________ _________________________________________________________________ _________________________________________________________________