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					   Psyc 689 Clin
Psychopharmacology

Introduction-Neuroanatomy
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@PSYC.TAMU.EDU
      – Web site:
        http://psychology.tamu.edu/courses/W
        ellman/689.html
      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)
 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)
    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
ECT
Psychosurgery
             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)
     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
 “Evolution” of Localization of
           Function




Phrenology         Brodman            Cortical Activity
   Bust      Cytoarchitectonic Map   During 2 nd Language
                                          Practice
                     Broca’s Area
• Patient “Tan” showed major
  deficit in speech (aphasia)
  following a stroke
  – Broca’s autopsy of Tan’s 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
  – Broca’s paper can be read at:
    http://psychclassics.yorku.ca/Broc
    a/perte-e
       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…
   – Penfield’s 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)
Hunger and Reward After Lateral
   Hypothalamic Stimulation
              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
                 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
           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)
          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
            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
   Midline Brain View
Motor        Sensory
               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)
           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)
  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
Primary Sensory and Motor
         Cortex
                       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
Divisions of Motor Cortex
Motor “Homunculus”
  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)
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)
 Occipital Lobe Neuropathology
• Cortical blindness
• Visual eye movement difficulties (area 8)
• Achromatopsia (rod vision, lacks color
  perception
• Visual neglect (agnosias)
• Gaze disorders
                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 RF’s 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
Primary Auditory Cortex
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
                  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
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
    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
                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
                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)
     Degenerative Disorders
• Certain diseases produce loss of brain
  neurons
  – Parkinson’s disease: loss of dopamine
    neurons
  – Huntington’s Chorea: loss of GABA/ACh
  – Alzheimer’s disease: loss of ACh neurons
                     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)
              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
    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)
  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)
             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

				
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posted:11/9/2011
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