Law of Initial Values Wilder, 1962

1
Law of Initial Values(Wilder, 1962)

• Intensity and duration of drug effect depends on
  the baseline
• Methylphenidate reduces hyperactivity in persons
  with high levels of basal activity but increases
  it in those with low levels
• Regression-to-the mean effects?
• placebo controls

2
What Determines Baseline?

• Cognitive demands
• Individual differences
• Genetics
• Gender
• Age

3
Yerkes-Dodson Law 1908

• As arousal increases performance increases. At
  some point increased arousal leads to decreased
  performance.
• As arousal increases there is a reduction of cues
  to regulate performance (narrowing of attentional
  focus).
• There is also increased distractibility
  (increased attentional shifts)

4
Arousal, Complexity, and Learning
5
State and Trait Anxiety

• State anxiety varies from second to second and
  from task to task.
• Trait anxiety characterizes an individuals
  general tendency to worry.

6
Neurochemistry of prefrontal function
- effects on attention, memory
Cools and Robbins, 2004
Seamans and Yang, 2004
7
NA-Behavior Relationship
8
Are the extremes functional?

• Delayed response task
• Requires focused attention
• Is affected when distractibility increases
• Attentional set-shifting
• Requires flexible attention
• Improves when distractibility increases

9
Neuromodulation

• signal-to-noise
• switching
• burst/single spike
• oscillations

10
Neuromodulators alter intrinsic properties of
networks
Marder and Thilumalai, 2002
11
Modulation of spinal locomotor circuit
Le Beau et al., 2005