Psyc 689 Clin Psychopharmacology

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Psyc 689 Clin Psychopharmacology

• Introduction-Neuroanatomy

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Instructor Contact Details

• Paul J. Wellman
• Office Psychology 248
• Phone
• 979-845-2557 (Office)
• 979-845-2581 (Dept)
• 979-845-4727 (Fax)
• 979-777-3163 (Cell)
• Email PJW_at_PSYC.TAMU.EDU
• Web site http//psychology.tamu.edu/courses/Wellm
  an/689.html

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Psyc 689 Course Details

• Lectures are Wednesday
• 9 am-12 pm
• Exams 2 exams each worth 100 points (exams will
  be taken in class)
• Readings are from Handbook of Clinical
  Psychopharmacology for Therapists (4e) by
  Preston, O Neal, and Talaga (2005)

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Overview Of Course Topics

• Neurophysiology
• Neurochemistry
• Neuroanatomy (functional and neurochemical)
• Basic principles of pharmacology
• Specific disorders
• Psychoses
• Anxiety
• Depression
• Issues of treatment
• Side effect profiles
• Subject characteristics (gender, age, health)
• Psychopharmacology Resources (PDR)

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Physical Approaches to Altering Behavior

• Trephining
• ECT
• Psychosurgery
• All are based on the idea that altering brain
  function can alter behavior
• Risk-benefit issues for these treatments

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ECT
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Psychosurgery
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Psychopharmacology

• Psychopharmacology is the study of the effects of
  drugs on the nervous system and on behavior
• The term drug has many meanings
• Medication to treat a disease
• A chemical that is likely to be abused
• An exogenous chemical that significantly alters
  the function of certain bodily cells when taken
  in relatively low doses (chemical is not required
  for normal cellular functioning)

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Development of Psychoactive Drugs

• Alcohol (?)
• Cannabis (THC)
• Opiates
• Caffeine (1300 Ethiopia)
• Cocaine (1200-1500 Incas cocaine isolated in
  1859)
• Nicotine (1556 Western Europe)
• Ether used as an inhalation toxicant
• Hallucinogens (peyote)
• Stimulants (amphetamine syn in 1887)
• Medicinal chemistry

http//itsa.ucsf.edu/ddrc/histdrg_frset.html
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Evolution of Localization of Function
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Brocas Area

• Patient Tan showed major deficit in speech
  (aphasia) following a stroke
• Brocas autopsy of Tans brain (1861) noted
  damage in the left hemisphere
• the lesion of the left frontal lobe was the
  cause of the loss of speech
• Case report conclusion was correct
• Brocas paper can be read at http//psychclassics
  .yorku.ca/Broca/perte-e

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Artificial Stimulation of Brain

• Neurons in a region can be artificially activated
  to assess the role of that region in behavior
• Electrical stimulation involves passing
  electrical current through a wire inserted into
  brain
• Cincinnati physician and brain stimulation
• Conducted in prostitute with bone cancer of skull
• Patient died, but not related to electrical
  stimulation
• Penfields cortical stimulation studies
  (Montreal)
• Chemical stimulation can involve infusion of an
  excitatory amino acid such as glutamate into a
  region
• A cannula implanted into a region can be used to
  deliver drug solutions into that region
• Chemical stimulation can be more specific than
  electrical stimulation (glutamate activates cell
  bodies, not axons)

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Hunger and Reward After Lateral Hypothalamic
Stimulation
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Neuroanatomy Terms

• The neuraxis is an imaginary line drawn through
  the spinal cord up to the front of the brain
• Anatomical directions are understood relative to
  the neuraxis
• Anterior (rostral) toward the head
• Posterior (caudal) toward the tail
• Ventral (inferior) toward the belly
• Dorsal (superior) toward the back (top of head)
• Location in brain
• Ipsilateral same side of brain
• Contralateral opposite side of brain

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Planes of Section

• The brain can be sectioned in three planes
• Each section provides a different view of the
  internal anatomy of the brain
• Sagittal
• Coronal (or transverse)
• Horizontal

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Two Nervous Systems

• The nervous system consists of two divisions
• The central nervous system (CNS) is comprised of
  the brain and spinal cord
• The peripheral nervous system (PNS) is comprised
  of the cranial/spinal nerves and peripheral
  ganglia
• PNS nerves project to target organs and to
  muscles (efferent)
• These nerves also carry sensory information to
  the brain (afferent)

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Views of the CNS

• Anatomical
• Nuclei and fibers
• Functional
• Sensory, motor, integrative
• Emotion, reward, memory, sleep and arousal
• Lesion studies, functional imaging studies
• Neurochemical pathways
• Dopamine, serotonin, glutamate, GABA, glycine

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Levels of the CNS

• Cerebral Cortex and brain hemispheres
• Cortical lobes (4 bone-defined, 2 internal)
• Gyri and sulci markers
• Fibers, tracts, commisures, nerves, ganglia,
  nuclei, fasciculi (us)
• Neurons
• Neuron components
• Synapses and neurotransmitters (NTs)
• Receptors (auto-, post-synaptic)
• Neuron membranes and associated channels
• Ligand-gated voltage-gated

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Midline Brain View
Motor
Sensory
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Cerebral Cortex

• The cerebral cortex forms the outer surface of
  the cerebral hemispheres
• Cortex surface is convoluted by grooves
• Sulci (small grooves)
• Fissures (large grooves)
• The bulges in cortex are termed gyri
• The cortex is primarily composed of cells, giving
  it a gray appearance
• The cortex is formed from 6 layers of cells
• Cortex can be divided into 4 lobes frontal,
  parietal, occipital, and temporal (limbic makes 5)

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Orbitofrontal Cortex

• Humans are able to interact socially and to
  understand social situations
• The analysis of social situations requires an
  intact orbitofrontal cortex
• Phineas Gage dynamite tamping rod penetrated
  orbitofrontal cortex
• Gage exhibited reduced inhibitions and
  self-concern
• Jacobsen reported calming action of frontal lobe
  damage in monkeys
• Led to the development of prefrontal lobotomy
  technique (Moniz)

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Frontal Lobe Neuropathology

• Paralysis (usually flaccid if upper body neuron)
• Paresis (weakness)
• Impaired dexterity
• Motor impersistence
• Subclinical catatonia and motor retardation
• Impairment smooth eye-tracking
• Elevated blink rate

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Primary Sensory and Motor Cortex
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Motor Cortex

• Multiple motor systems control body movements
• Walking, talking, postural, arm and finger
  movements
• Primary motor cortex is located on the precentral
  gyrus
• Motor cortex is somatotopically organized (motor
  homunculus)
• Motor cortex receives input from
• Premotor cortex
• Supplemental motor area
• Frontal association cortex
• Primary somatosensory cortex
• Planning of movements involves the premotor
  cortex and the supplemental motor area which
  influence the primary motor cortex

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Divisions of Motor Cortex
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Motor Homunculus
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Parietal Lobe Neuropathology

• Issues in receptive speech, naming, comprehension
• Tactile discrimination difficulty
• Vestibular processing (Area 2)
• Route finding issues (spatial)
• Calculation problems
• Right parietal lobe spatial neglect
• Time interval estimate difficulties
• Prosopagnosia (w/ inf. Temporal lobe)

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Visual Cortex Function

• V4 responds to color and
• perception
• V5 responds to movement
• TEO involved in color discrimination, 2-d
  pattern discrimination
• TE neurons respond to 3-d
• (a face or a hand)

form
objects
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Occipital Lobe Neuropathology

• Cortical blindness
• Visual eye movement difficulties (area 8)
• Achromatopsia (rod vision, lacks color perception
• Visual neglect (agnosias)
• Gaze disorders

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Receptive Fields

• Receptive Field (RF) Those attributes of a
  stimulus that will alter the firing rate of a
  given sensory cell
• Can measure the RF at each level of sensory
  system
• There are as many RFs as there are cells in a
  sensory system
• Look for commonalities of fields at each level of
  the system
• Cortex is organized into columns, with each
  column sharing an attribute

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Primary Auditory Cortex
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Temporal Lobe Neuropathology

• Misidentification syndromes Prosopagnosia
• Amnestic syndromes (hippocampus)
• Central deafness (areas 41,42)
• Wernicke related dysphasias (Area 22)
• Receptive
• Conductive type
• Hypo- and hypersexuality
• Panic/fear states

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Limbic System

• The limbic system is comprised of
• Hippocampus involved in learning and memory
• Amygdala involved in emotion
• Mammillary Bodies
• The fornix is a fiber bundle that interconnects
  the hippocampus with the mammillary bodies

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Hippocampal Damage and Amnesia

• Severe anterograde amnesia follows bilateral
  damage to the hippocampus
• Patient H.M. suffered from severe epilepsy
• To minimize his epilepsy, H.M.s surgeons removed
  his medial temporal lobe (including the
  hippocampus)
• Following surgery, H.M. showed severe anterograde
  amnesia
• No retention for events that have occurred since
  1953
• Can recall events that occurred prior to 1953
• H.M.s amnesia was attributed to hippocampal
  damage
• Patient Boswell herpes encephalitis led to
  bilateral damage to the mesial temporal lobe
• Amygdala, hippocampus, entorhinal cortex)
• Severe anterograde AND severe retrograde amnesia

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Emotion and the Amygdala

• Threat stimuli increase neural firing and fos
  activity within central nucleus of the amygdala
• Humans show increased amygdala activity (PET
  studies)
• Lesions of central nucleus diminish emotional
  responses
• Reduced fear responses to threat stimuli
• Reduced chance of developing ulcers to stress
• Reduced levels of stress hormones
• Electrical stimulation of central nucleus induces
  fear and agitation
• Central amygdala nucleus is important for the
  expression of emotional responses to aversive
  stimuli

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Diencephalon

• Diencephalon consists of
• Thalamus contains nuclei that receive sensory
  information and transmit it to cortex
• Hypothalamus contains nuclei involved in
  integration of species-typical behaviors, control
  of the autonomic nervous system and pituitary

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The Basal Ganglia

• The basal ganglia are a collection of subcortical
  nuclei that lie just under the anterior aspect of
  the lateral ventricles
• Ganglia is a misnomer (term refers to
  collections of cell bodies in periphery)
• Basal ganglia consist of the caudate nucleus, the
  putamen and the globus pallidus
• Input to the basal ganglia is from the primary
  motor cortex and the substantia nigra
• Output of the basal ganglia is to
• Primary motor cortex, supplemental motor area,
  premotor cortex
• Brainstem motor nuclei (ventromedial pathways)

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Degenerative Disorders

• Certain diseases produce loss of brain neurons
• Parkinsons disease loss of dopamine neurons
• Huntingtons Chorea loss of GABA/ACh
• Alzheimers disease loss of ACh neurons

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Mesencephalon

• The mesencephalon (midbrain) consists of
• Tectum is the dorsal portion of midbrain
• Superior and inferior colliculi are involved in
  the visual and auditory systems
• Tegmentum is that portion of the midbrain located
  under the tectum and consists of the
• Rostral end of the reticular formation
• Periaqueductal gray
• Red nucleus
• Substantia nigra (projects to striatum)
• Ventral tegmental area (part of
• reward circuit)

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Metencephalon

• Metencephalon consists of the
• Pons
• Contains the core of the reticular formation
• The pons is involved in the control of sleep and
  arousal
• Cerebellum is involved in motor control

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Neural Control of REM Sleep

• The pons is important for the control of REM
  sleep
• PGO waves are the first predictor of REM sleep
• ACh neurons in the peribrachial pons modulate REM
  sleep
• Increased ACh increases REM sleep
• Peribrachial neurons fire at a high rate during
  REM sleep
• Peribrachial lesions reduce REM sleep
• Pontine ACh neurons project to the thalamus
  (control of cortical arousal), to the basal
  forebrain (arousal and desynchrony), and to the
  tectum (rapid eye movements)
• Pontine cells project via magnocellular cells
  within medulla to the spinal cord release
  glycine to inhibit alpha-motoneurons (induce REM
  motor paralysis or atonia)

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Sleep and Neurotransmitters

• Sleep function is altered by
• Norepinephrine (arousal)
• Serotonin (promotes sleep)
• Dopamine (arousal)
• Acetylcholine (in cortex arousal)
• Histamine (arousal)
• GABA (promotes sleep)
• Opioid/opiates (promote sleep)

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Myelencephalon

• The myelencephalon consists of the
• Medulla oblongata
• The medulla is the most caudal portion of brain
  and is rostral to the spinal cord
• The medulla contains part of the reticular
  formation
• The nuclei of the medulla control vital functions
  such as regulation of the cardiovascular system,
  breathing, and skeletal muscle tone