Brain Anatomy: Clinical Examples

Visual Pathways into the CNS

In the visual system, the retina at the back of the eyeball contains the photoreceptors that detect light, along with other types of cells that process the visual signal. The output from the retina to the brain is from the retinal ganglion cells, whose axons project to the thalamus via the optic nerve, optic chiasm, and optic tract.

Refer to figure 10.34 on p. 350 of the textbook. The retina can be divided into two halves:  the nasal retina, which is closer to the nose, and the temporal retina, which is closer to the temporal bone and in a lateral position.  See which retinal ganglion cells encode information about the right visual field (indicated by the red lines in the schematic drawing). Essentially, the right visual field is "looked at" by the left temporal retina and the right nasal retina. The projection into the brain is organized so that all of the information about the right visual field will end up in the left thalamus and left visual cortex. This is achieved because the axons from ganglion cells in the nasal retina cross over at the optic chiasm, while axons from the temporal retina do not cross to the other side.

The clinical significance of this anatomical arrangement is that certain disorders may cause partial visual field losses known as hemianopias (also called hemianopsias).  The pituitary gland sits just behind and below the optic chiasm. Sometimes tumors in the pituitary gland will specifically compress axons in the center of the optic chiasm.  This causes a loss of peripheral vision (specifically the term is bitemporal hemianopia).

Be able to draw a schematic of the path taken by the axons from the nasal and temporal halves of the retina, and know the effects of lesions affecting the optic nerve, optic chiasm, and optic tract.

Upper Motor Neuron Disorders

The primary motor cortex is located in the precentral gyrus. This region of the brain contains neurons that are involved in initiating voluntary movements. A key feature about this region (and the adjacent primary somatosensory cortex in the postcentral gyrus) is that neurons are organized somatotopically. This means that neurons that control muscles in adjacent parts of the body are next to each other in the primary motor cortex.  Essentially, there is a map of the body in the brain.  As shown in figure 13.10 on p.427, regions of the body with more fine motor control (such as the hand) have a higher degree of representation in the motor cortex. 

The neurons whose cell bodies are located in the primary motor cortex are some of the largest neurons in the body. The axons of these neurons extend down to the spinal cord where they make direct synaptic connections with somatic motor neurons (cells that innervate skeletal muscles). A clinical term for these cells in the motor cortex is upper motor neurons (with the somatic motor neurons being the lower motor neurons). Another name for these cells is pyramidal neurons, because their axons cross in a structure on the ventral surface of the medulla known as the pyramids.

The axon bundle containing the axons of the upper motor neurons is termed the corticospinal tract. Axons in the first part of the corticospinal tract are found in a region of white matter called the internal capsule. The internal capsule can best be seen in the horizontal section of the brain, dividing different nuclei in the basal ganglia (but is also visible in one of the frontal sections). Most of the axons (particularly those that project to somatic motor neurons innervating the limbs) cross over to the opposite side of the body at the medulla oblongata, and then continue in the spinal cord in the lateral corticospinal tract.  This is schematized in the figure at right.

Damage to neurons of the corticospinal tract is known clinically as an upper motor neuron disorder.  An upper motor neuron disorder will affect motor control in different ways, depending on the location of the damage. If a stroke causes a lesion in the primary motor cortex, motor function on the opposite (contralateral) side of the body will be affected. If on the other hand, there is damage to the lateral spinal cord where the lateral corticospinal tracts are located, this will cause a motor defect in the limbs on the same (ipsilateral) side of the body.

Damage to the upper motor neurons causes two kinds of effects. The predominant effect initially is a loss of motor function, either paralysis or muscle weakness. These changes result from loss of excitatory input to the somatic motor neurons, and are termed a negative signs. However some of the axons that descend in the corticospinal tract provide inhibitory input to neurons in the spinal cord, and loss of this input leads to abnormal increases in certain motor behaviors, or positive signs.  An example of a positive sign is exaggerated reflexes (hyperreflexia).  Another positive sign is an increase in stiffness, or muscle tone (hypertonia).  Muscle tone is defined as the resistance of the muscle to passive stretch.

Parkinson's Disease

Parkinson's disease is a neurodegenerative disease affecting the basal ganglia, which are involved in the control of movement.  The disease is diagnosed by observing a set of characteristic symptoms:  resting tremor, bradykinesia, and hypertonia.

• Resting tremor is an oscillating movement that occurs when the patient is trying to be still. The tremor usually disappears when the patient undertakes a voluntary movement with the limb. This distinguishes it from other disorders involving tremor in which the tremor persists during movement (essential tremor) or is specifically associated with movement (intention tremor in cerebellar disorders).
• Bradykinesia means slowness of movement. The patient might initially experience bradykinesia as a weakness or stiffness in one limb.
• Hypertonia (excessive muscle tone) also occurs in Parkinson's disease. This will manifest itself as rigidity or stiffness.
  

Other typical features seen as the disease progresses are a stooped posture and slow, shuffling gait. As it becomes more and more difficult to initiate movement, the patient will start to show akinesia, or a lack of movement.  Lack of movement of the facial muscles gives the patient the appearance of having a mask-like, frozen look.

For many patients, the initial presentation is asymmetric, meaning only one limb or one side of the body is affected. This is what is illustrated in the video clip, from a clinical practice article in the New England Journal of Medicine (Nutt JG and Wooten GF. Diagnosis and Initial Management of Parkinson's Disease. N Engl J Med 2005;353(10):1021-7).

The second video clip shows a patient in whom the disease is much more advanced. The patient has a strong resting tremor in the arms, and a stooped posture. Akinesia manifests as "freezing of gait", in which the patient has great difficulty in taking a step forward. Amazingly, the second part of the video shows the patient is still able to ride a bicycle. (Snijders, A. H. and Bloem, B. R. Cycling for Freezing of Gait. N Engl J Med 2010;362: e46).

Neurodegeneration in Parkinson's Disease

Parkinson’s disease is caused by a degeneration of neurons in the substantia nigra of the midbrain.  Substantia nigra means "black substance, and it is easily reconizable as the pigmented region that stretches across the midbrain in a frontal section of the brain.  These neurons form connections with the basal ganglia and release the neurotransmitter dopamine.  Parkinson's disease is considered a disorder of the basal ganglia because the major projection from the substantia nigra is to nuclei of the basal ganglia*. The schematic provides a simplified illustration of the connectivity of the basal ganglia.  The basal ganglia receive inputs from the motor cortex (and other brain regions), and then project back to the motor cortex via the thalamus. The substantia nigra is interconnected with nuclei in the basal ganglia.  The basal ganglia integrate these multiple inputs to modulate the output of the motor cortex. Some of the connections are excitatory and some are inhibitory. The loss of input from dopamine-releasing neurons in the substantia nigra alters the balance of the output from the basal ganglia to the motor cortex, and this underlies the symptoms that are seen.

Parkinson's disease can be treated by restoring the dopamine that is lost from the basal ganglia when neurons from the substantia nigra degenerate. Dopamine itself cannot be used because it doesn't cross the blood-brain barrier. Instead, patients are treated with L-DOPA (also known as levodopa), a dopamine precursor that can cross the blood-brain barrier.

Optional
This video shows the effectiveness of a treatment for Parkinson's disease called deep brain stimulation (DBS).  DBS changes the activity of neurons in the basal ganglia circuitry in ways that are not fully understood.  The treatment doesn't work for all Parkinson's patients, but for some individuals, DBS can have a profound effect on symptoms.

*Wikipedia (and perhaps some other sources) define the basal ganglia as "subcortical nuclei", a definition that allows the substantia nigra to be lumped in with the cerebral nuclei of the basal ganglia.  For our purposes, the basal ganglia consist of the three nuclei (caudate, putamen, globus pallidus--you don't need to know the specific names) located deep in the cerebrum.  Functionally speaking, the substantia nigra is part of the basal ganglia circuitry; but anatomically speaking, it is a distinct nucleus located in the midbrain.