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CHAPTER 11 Topping It O: The Neocortex 211
Broca’s area
Why is Broca’s area on one side only? Speech involves control of muscles like the
tongue and vocal cords on the center line of the body, whose operation in speech
uses symmetrical motor control on both the left and right sides. Interhemispheric
communication is slow, making it particularly dicult to produce rapid speech.
And given the brains’ symmetrical control aspects, one side of the brain may have
evolved to dominate speech production.
Wernicke’s area
Wernicke’s area is at the junction of the temporal and parietal lobes, near the
angular gyrus. This area is a high-order audio-processing region and receives
input that starts in the primary auditory cortex (Heschl’s gyrus in mid-superior
temporal lobe, area 41 in Figure 11-7) and passes through high-order auditory
association cortex around the primary auditory cortex. Damage to Wernicke’s area
doesn’t interfere with rapid speech production, but the speech produced doesn’t
make sense. Damage to this area also compromises speech comprehension.
Interestingly, the homologous area of the right hemisphere to Wernicke’s in the
left appears to be involved in processing meaningful intonations in speech.
Patients with damage to this area can understand speech, but they lack the ability
to grasp nuances like ironic and other tones of voice.
Taking in the big picture: Spatial processing
The right side of the brain appears to be superior to the left in processing visual
imagery and visual attention. Damage to the right parietal lobe prevents people
from paying attention to things in the left visual eld. An area in the right medial
temporal lobe called the fusiform face area is crucial for recognizing faces. Damage
to the homologous area on the left side doesn’t aect facial recognition.
Managing with two brains in one head
Many decades ago, pop psychology was full of ideas to help you get in touch with
the creative right side of your brain. Your right side had supposedly been repressed
by formal education’s emphasis on left-brain language and analytical activities.
Pop psychology also proposed that an individual’s dominant side is the basis for
personality, skills, and vocation.
Thinking that, for example, writing poetry or ction, a left-brain language skill,
doesn’t involve high creativity is preposterous. Over the past decadethe idea that
people are left-brained orright-brained has been disproven. In 2013, a team of
neuroscientists reviewed previous research along with new evidence and debunked
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212 PART 2 Controlling Muscles, Movement, and Survival
several previous ndings. Thanks to the corpus callosum, whose axons intercon-
nect the two hemispheres, cognitive abilities, logic, and creativity involve both
sides of the brain.
That said, lateralization and specializations do exist, and they are phylogeneti-
cally very old, appearing even in birds. Song production in songbirds relies more
on structures in the left sides of their brains that the right. Lateral specialization
is more extreme in humans, mostly because of language. But each side of the brain
gives we humans unique capabilities, and we use both sides. This is an advantage,
as we discuss in the next section.
Appreciating the style of each hemisphere
Consider what scientic evidence says about the dierence between the two
hemispheres of the brain. Some of the original ndings about hemispheric asym-
metry suggested that the right hemisphere is more holistic, and the left is more
analytical.
Holistic processing
Holistic processing deals with the big picture and categorizes by the whole. For
example, you can recognize your friend’s face even if they shave o their mous-
tache or put on sunglasses. In fact, in a casual encounter with someone you know,
you may not even notice these changes. The right hemisphere appears to operate
in a case-based style of reasoning, identifying people by matching the current
stimulus to the set of people you know.
Analytical processing
Analytical processing is rule based. It looks at particular features individually. For
example, if you were asked to describe a stranger at a crime scene, you’d likely be
asked to go through a set of attributes: height, weight, skin color, sex, age, and so
forth. The police would search for their suspect based on this set of criteria.
Processing by rules
The relevance of this to brain operation is that language is a rule-based system.
It’s a sequence of discrete words with denable meanings that get strung together
according to rules of grammar. The word denitions and grammar types must be
put together to extract the meaning. This is a left-brain type of skill. Some have
argued that it’s similar to using the dominant right hand (controlled by the left
hemisphere) to perform a sequence of specic steps to make a tool.
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CHAPTER 11 Topping It O: The Neocortex 213
Remembering the layout of a scene, however, requires a more literal memory of
spatial relationships— describing a scene isn’t easy to do using rules because you
have to account for metrics such as distances and sizes. The holistic right brain
seems to be able to distinguish dierences between faces, or between poodles and
terriers, even though the parts of the objects being compared are more or less the
same, and more or less in the same locations, as one would describe using
language.
Considering Sex and the Brain
Economist Larry Summers famously received a no condence vote from the fac-
ulty and resigned as president of Harvard University in 2005. He controversially
suggested that given the dierences between male and female brains in mathe-
matical ability, it may be no accident that women were underrepresented in STEM
departments. Are there dierences between male and female brains? And, if so,
what do the dierences mean? Read on.
Sizing up the male and female brain
One measurable dierence is average brain size. Males have an average brain vol-
ume of about 1,260cm
3
; females, around 1,130cm
3
. Although the brain does scale
with physical size, the brains of males average about 100 g more than those of
EPILEPSY AND SPLIT-BRAIN SURGERY
The split-brain operations that were performed in the late 1950s to limit epileptic sei-
zures revealed a lot about dierences between brain hemispheres in humans. The
operations involved sectioning the corpus callosum (the 200-million-axon ber tract that
connects the neocortex on the left with the right). At rst, after the operations, the
patients showed almost no dierence in behavior, except that they had far fewer sei-
zures, the goal of the surgery.
More careful experiments showed that information about stimuli transiently presented
to the left visual eld, which goes to the right half of the brain, can’t reach the left hemi-
sphere. The split-brain subject cannot verbally say anything about the stimulus.
However, they can point to a matching picture with their left hand, controlled by the
informed right brain. They were also much better at solving spatial puzzles with their
left hands, controlled by the right hemisphere, than by their right hands.
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214 PART 2 Controlling Muscles, Movement, and Survival
females of the same body size. However, given the large variation in brain size and
measures of intelligence, a 100 g dierence wouldn’t mean any signicant dier-
ence in intelligence.
Zeroing in on certain areas and
lateralization
Sex dierences are more obvious in particular brain regions. Males average greater
volumes in the neocortex, cerebellum, and amygdala, while females average a
larger hippocampus. Males may have a higher ratio of gray to white matter com-
pared to females. None of these dierences would statistically predict signicant
dierences in intelligence.
Another dierence between male and female brains is the extent of lateralization
and specialization. Imaging studies show that females display more bilateral acti-
vation while doing tasks, indicating greater connection between the hemispheres.
Females also generally recover better than males from brain damage during
development and strokes in adulthood that damage the brain unilaterally.
If male brains are more lateralized, then the left and right sides may be more spe-
cialized. The downside is that males are more susceptible to brain injury, but the
upside may be some specialized skills.
Although there’s no statistical dierence in average IQ between males and
females, data show females do better than males in language skills, while males
do better than females in visuo-spatial skills. Researchers don’t know whether
dierences result from cultural and education dierences or how much is from
inherent brain lateralization dierences.
Besides verbal and spatial IQ, many other types of intelligence exist that don’t t
so neatly into either of those categories, such as artistic and musical abilities,
communication, social, and emotional skills.
Knowing the role of hormones
Male and female brains show their dierences because of sex-specic hormones,
such as testosterone, estrogen, and oxytocin that aect brain development and
function. In mammals, female is the default developmental phenotype in sexual
dierentiation. This means that without either testosterone or estrogen, the
mammal’s body plan will develop as female. In typical male development in utero,
a big mid-gestation surge of testosterone inuences body parts and the brain.
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CHAPTER 12 Delving into Motor Systems Disorders 215
Chapter12
Delving into Motor
Systems Disorders
N
eurological disorders are among the most disabling health problems in the
United States and worldwide. Neurological disorders in which the main
symptoms cause movement problems are referred to as motor or move-
ment disorders. Many factors can contribute to these disorders, including genetic
abnormalities, infections, immune dysregulation, and injury that can involve
damage of muscles, motor neurons, the spinal cord, or brain. This chapter dis-
cusses disorders of motor systems, their underpinnings where known, how they
aect the nervous system, and how they’re treated.
Leading to Motor Disorders
Motor disorders are a subcategory of neurodevelopmental disorders. They involve
physical disabilities in which individuals have limited function of one or more
limbs, a disability in learning or making skilled movements, or uncontrolled or
IN THIS CHAPTER
»
Looking at physical disabilities
»
Examining diseases of the muscles
»
Exploring neuromuscular junction
diseases
»
Seeing what happens when motor
neurons are damaged
»
Understanding diseases that aect
basal ganglia
»
Knowing about strokes and brain
injuries
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216 PART 2 Controlling Muscles, Movement, and Survival
involuntary movements. During development, motor disability can occur from
genetic disorders, infections, drug exposure, or fetal developmental accidents.
Motor disorders can occur throughout the lifespan.
Here we describe several developmental and lifetime motor disorders.
Early motor disabilities and disorders
Motor and other dysfunctions that exist at birth or manifest shortly after are
called congenital disorders. These can result from genetic abnormalities, infections,
injuries, or exposure to teratogens that cause birth defects. Premature birth and
problems during delivery can also produce motor disorders through trauma or
oxygen deprivation. Accidents and infections can occur before, during, and after
birth that produce motor disabilities.
About 5 percent of young children have poor motor coordination that interferes
with performance in school, social interactions, and playing sports. We describe
the most common developmental disorders in the next sections.
Neural tube defects
One of the most common congenital birth defects aecting the nervous system is
the group of neural tube defects (NTDs), with an incidence of 1 per 500 births.
NTDs occur when the neural tube fails to close completely during embryonic
development. Chapter3 describes neural tube development.
The most common NTD is spina bida in which the posterior (spine) neural tube
closure is incomplete. In spina bida, neurosurgery can be performed to close the
gap, and in some cases, reconstruct the spine. Many children with spina bida
have some degree of lower limb weakness or paralysis. For those children, physi-
cal therapy to help strengthen muscles, or the use of braces, crutches, or mobility
devices can improve independence.
The incidence of NTDs can be decreased by up to 70 percent when the mother’s
diet includes folic acid. Today, 81 countries worldwide have mandatory folic acid
fortication of grain products to prevent NTDs.
Cerebral palsy
Cerebral palsy is a commonly occurring neurological motor impairment (about
1 per 500 children). Cerebral palsy (which means paralysis or tremors) refers to
symptoms of the disorder that can be caused by numerous factors. Cerebral palsy
is often associated with a brain lesion that occurs prenatally — and in some cases
may involve maternal infection.
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CHAPTER 12 Delving into Motor Systems Disorders 217
Dierent causes lead to many dierent manifestations of cerebral palsy. Although
there’s no cure for cerebral palsy, treatments that include medications to relax
muscle contractions or reduce spasticity, and physical and occupational therapies,
can improve a child’s quality of life.
Injuries and infections
Infectious diseases and prenatal, birth, and early childhood injuries cause many
motor disorders, including the following:
»
TORCH complex: Infections which cause congenital abnormalities that can
include motor decits are referred to as the TORCH complex. Infections include
toxoplasmosis, other (for example, HIV, syphilis, and hepatitis B), rubella,
cytomegalovirus (CMV), and herpes simplex virus. Many maternal viruses can
cross the placenta and can lead to complications such as low birth weight,
microcephaly, and seizures, causing mental disability and coordina-
tion problems.
»
Acquired brain injuries: Injuries that occur after the neonatal period but
during childhood are referred to as acquired brain injuries. They include
traumatic injuries such as blows to the head, weapon injuries, and injuries
from shaking, as well as nontraumatic injuries such as tumors and infections.
Developmental brain plasticity (refer to Chapter3) may partially alleviate symp-
toms from these injuries over time, but some motor decits, such as poor coordi-
nation, may not fully recover.
Lifespan motor disorders
Risks for motor dysfunction increase with age. Risks includes cumulative expo-
sure to environmental toxins, declines in vascular function, nervous system
tumors, and some genetic diseases that manifest later in life. Some genetic dis-
eases manifest in adulthood without any known environmental trigger. Other
genetic diseases may produce susceptibility to develop motor dysfunctions that
will manifest later depending on environmental factors.
The most well-known lifespan neurological disorder is Alzheimer’s disease (refer
to Chapter 15). Although its earliest symptoms aren’t motor problems, later
symptoms include loss of motor control and even compromise of the autonomic
nervous system.
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218 PART 2 Controlling Muscles, Movement, and Survival
Failing Forces: Muscle Diseases
Neuromuscular diseases can impair muscle functioning because of pathologies in
the muscle, motor neurons, or neuromuscular junction. These diseases usually
manifest initially as weakness and can proceed to paresis (partial paralysis) and
full paralysis. Many of these typically aren’t associated with cognitive, autonomic,
or organ dysfunction until end-stage phases.
Diseases that aect the muscle directly are called primary myopathic (muscular)
disorders. Myopathies called dystrophies are characterized by progressive muscle
degeneration due to the muscle’s inability to repair and regenerate normally.
Severe dystrophies begin with weakness, progress to paralysis, and can eventually
be fatal from respiratory failure. These diseases can be congenital, usually from
genetic abnormalities, from infections, or from the immune system attacking the
muscle.
Muscular dystrophy
Muscular dystrophy (MD) is characterized by progressive skeletal muscle weakness
and the death of muscle tissue. The most severe and common form of MD is
Duchenne muscular dystrophy that occurs in 1 per 3,500 to 6,000 boys and 1 per
50 million girls. The Duchenne mutation is located on the X chromosome in a gene
that codes for the protein dystrophin, a structural component of muscle tissue.
Duchenne MD symptoms usually appear in boys by age 6 with symptoms includ-
ing progressive weakness of the legs that later includes the arms. In the course of
MD, muscle tissue degenerates. Most individuals are wheelchair dependent by age
12, with a life expectancy of 20 to 30 years.
The FDA has approved the rst recombinant gene therapy for the treatment of
pediatric patients with Duchenne MD.It involves introducing a functional gene
region into the cells of the individual. The gene delivered is a shortened protein
that contains selected domains of the normal dystrophin protein.
Other types of muscular dystrophy include Becker MD, myotonic MD, and Emery-
Dreifuss MD.All types of MD predominantly aect males, but females typically
carry the disease gene. MD also is associated with disorders in autonomic
regulation.
Inammatory myopathies
Inammation of the muscles is called myositis. Chronic inammation of the
muscles can occur due to infection, resulting in polymyositis. This produces an
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CHAPTER 12 Delving into Motor Systems Disorders 219
inammatory myopathy associated with weakness in the shoulders and hips due
to loss of muscle mass. Myositis and polymyositis are thought to be autoimmune
disorders, potentially triggered by viral infection.
Autoimmune disorders
In autoimmune disorders, people produce antibodies and T cells that mistake
regions of their own (self) proteins as invaders. Protein sequences that activate
the immune system are called antigens. This leads to a destruction of the tissue
where the antigen is present. One hypothesis is that autoimmune disorders occur
through molecular mimicry. A part of a protein (antigen) from an infectious
invader (virus or bacteria) is similar to a region of a self-protein made in the body.
Mounting an immune response against the invader also leads to an autoimmune
attack on the body’s own protein and tissue.
Disrupting the Neuromuscular Junction
Neuromuscular junction disorders aect synaptic transmission from motor neurons
to the muscle motor end plate, which is responsible for contracting the muscle in
response to neurotransmitter release from the motor neuron (refer to Chapters6
and7). Myasthenia gravis and Lambert–Eaton syndrome are examples of neuro-
muscular junction disorders.
The neuromuscular junction is also the target of toxins that disrupt synaptic
transmission, several of which are used clinically to treat movement and pain
disorders. The following sections discuss what you need to know.
Myasthenia gravis
Myasthenia gravis (MG) is an autoimmune disorder having an incidence of about
30 new cases per million people per year. The majority of MG is caused by auto-
antibodies (antibodies that recognize self-proteins as antigens) against acetylcho-
line receptors at the muscle end plate. This lowers the number and activity of the
acetylcholine receptors, reducing the muscle response and decreasing muscle
contraction. About 15 percent of individuals with MG also have autoantibodies
against the muscle specic kinase MuSK.
The hallmark symptom of MG is muscle weakness that worsens with activity but
improves with rest. Symptoms are associated with muscles that control eye move-
ment (causing eyelid drooping called ptosis), facial expressions, chewing, swal-
lowing, and speech. Respiratory and limb movements can also be aected. In a
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220 PART 2 Controlling Muscles, Movement, and Survival
myasthenic crisis, respiratory muscles can be paralyzed, which is life threatening
and may require assisted ventilation.
Although MG is an autoimmune disease, the pathogen that causes it hasn’t been
identied. Genetic susceptibility includes specic human leukocyte antigens
(HLAs). MG is associated with abnormalities of the thymus, which produces T
cells, and is sometimes stabilized by removal of the thymus.
MG symptoms can be alleviated with acetylcholinesterase inhibitors that increase
the levels and lifetime of acetylcholine in the synaptic cleft. MG is also treated
with immunosuppressant therapies. New FDA-approved biologics have been
developed for MG.Biologics are sugars, DNA, or proteins, like monoclonal anti-
bodies that are produced in the laboratory in cells and puried. Injected biologics
can decrease auto-antibody production in MG by targeting specic immune
responses and cells.
Lambert–Eaton syndrome
Lambert–Eaton myasthenic syndrome (LEMs) is an autoimmune disorder with anti-
bodies against the presynaptic voltage-gated calcium channel. This leads to
decreased release of acetylcholine and decreased muscle contraction, initially
aecting lower limbs. LEMS is often seen in patients with small cell lung cancer.
The FDA-approved drug diaminopyridine is a potassium channel blocker used for
the treatment of LEMS.
Immunosuppressant drugs and biologics are used to reduce the immune response
in autoimmune disorders. Responses to immunosuppressants can distinguish MG
and LEMS from other myasthenic syndromes.
Neurotoxins and clinical uses
Several naturally occurring neurotoxins produced by microorganisms and animals
can aect the neuromuscular junction. Here are some examples of toxins that
produce inhibition of muscle contraction and paralysis:
»
Botulinum neurotoxin (Botox) prevents the release of acetylcholine. Botox is
known for cosmetic use. Its medical uses include treatment of spasticity,
chronic migraine, cervical dystonia, and incontinence.
»
Toxins in cobra snake venom block activation of the acetylcholine receptor.
»
Latrotoxin from black widow spider venom depletes acetylcholine.
»
Cone snail toxins (conotoxins) inhibit synaptic ion channels. Conotoxin is used
to block pain signaling pathways.
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