Effects of Temporal Lobe Amnesia, Aging and Awareness on Human Eyeblink Conditioning John Disterhoft
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1 Eyeblink Conditioning Across Species Effects of Temporal Lobe Amnesia, Aging and Awareness on Human Eyeblink Conditioning John Disterhoft Department of Physiology Institute for Neuroscience Northwestern University Medical School Chicago, IL Late in Training (CR) tone airpuff Pseudoconditioning controls. Hippocampus dependent. The same task can be used in humans, rabbits, and rats. Humans, rabbits, and rats show similar age related impairments. Reflectance tone airpuff (tone) airpuff Eyeblink Conditioning is Hippocampally-Dependent Amnesic Patients are Impaired in Acquiring Eyeblink Conditioning Task % CRs Hippocampus (n=9) Neocortex (n=7) Sham (n=11) session 6 5 McGlinchey-Berroth et al s e s n o p s e R 3 d e n 2 o i t i d n Gabrieli, McGlinchey-Berroth, Carrillo, Gluck, Cermak & Disterhoft Behav Neurosci o vol.19, C 1 % 5
2 Carrillo, Gabrieli, Hopkins, McGlinchey-Berroth, Fortier, Kesner, & Disterhoft Behav Neurosci vol.115, December 21 Carrillo, Gabrieli, Hopkins, McGlinchey-Berroth, Fortier, Kesner, & Disterhoft Behav Neurosci vol.115, December 21 Clark & Squire Science vol.28, April 1998 Clark & Squire Psychological Science vol.1, 1999
3 MMovie Questions: PPlease answer true or false to the following statements about the movie you just finished watching. 1 The main character in this movie is played by the actor named Charlie Chaplain. T F 2 The main character falls down a snowy hill and turns into a giant snowball. T F In one scene, a dog was eaten by a hungry man. T F A bear was shot and killed. T F A shoe was cooked and eaten for Thanksgiving dinner. T F There was a drinking contest between two men. T F The main character finds a new pair of shoes in the snow. T F One man s coat catches on fire. T F A hungry man thought he saw someone turn into a chicken. T F One man dies in an avalanche. T F Lovibond & Shanks J Exp Psych: Animal Behav Processes vol.28, January 22 Correlation of reported awareness with performance in delay EBC Carrillo, Gabrieli & Disterhoft Psychobiology vol.28, 2 l Hilgard et al ( 37):( subjects who reported awareness of which was reinforced showed better differential EBC in delay discrimination l Ross & Nelson ( 73):( In summary, some addt l cognitive or awareness process, which are sensitive to a variety of variables that do not affect single-cue conditioning, appear to be involved in differential conditioning l Carrillo et al ( 99):( performance of a verbal shadowing task or watching a silent movie had a significant effect on a two tone delay discrimination task No correlation of awareness with EBC performance l Grant ( 73):( awareness of - contingencies is not sufficient and may not be necessary to produce EBC or differential delay conditioning l Frcka ( 83): no significant relationship between measures of awareness and delay discrimination l Clark & Squire ( 98):( successful trace discrimination conditioning dependent upon awareness of - contingency, but successful delay discrimination was not dependent upon such awareness Questions: Are learning deficits which interact with awareness an agedependent phenomenon? Is awareness related to successful acquisition of trace and/or delay discrimination?
4 Learning Impairments in Aging Rabbits Are Heterogeneous Percent CRs 1 A 8 < 12 mo 24 mo 3 mo 6 36 mo 4 2 Percent severely-impaired B Aging Affects Eyeblink Conditioning in the Rat Young (6 mo)senecent (34-35 mo)old (2 % s YoungMiddleOld% learne Daily 8 trial sessions Age (mo) Thompson, Moyer and Disterhoft (1996) Neurobiol Aging 17: Knuttinen et al., Neurobiology of Aging, ms 125 ms 1 ms ms 25 ms 5 5 ms 1 ms 1 ms 1 1 ms 1 ms Total subjects: 138 (74 young; 64 aging) Mean age: young= 25; aging= 65 METHODS l 4 differential conditioning paradigms with either tone or static noise as + l Training consisted of 6 + and 6 - trials randomly presented; subjects instructed to watch a silent movie (Gold( Rush) l Eyeblink measures recorded via integrated and rectified EMG responses l Following conditioning: subjects answered questions about movie content AND about temporal relationships between the +, -, and Sample Eyeblink Discrimination Trials in a Human Subject Averaged trials for a young trace 1 subject. 1 + and 1 - trials per block. + - block1 + Reflectance block2 block (tone) (airpuff) block4 block5 - Reflectance (tone) (airpuff) block6 1 ms + -
5 Number Correct Stimulus Contingencies 1 17 Number Correct Movie Content YOUNG AGING AWARE UNAWARE Percent of Aware Subjects Awareness is Age-Dependent Awareness in Discrimination Learning Aging Aware Young Aware Aging Unaware Young Unaware trial blocks 2 trial blocks Awareness in Discrimination Learning Young Aware Aging Aware Aging Unaware Young Unaware trial blocks 2 trial blocks Age-related Effect in but not Discrimination Block 6 Aging Block Young Aging Young Block 6 Block FINDINGS l Awareness is essential for successful acquisition of both trace and delay discrimination EBC l Age-dependent deficit in trace, but not in delay discrimination EBC l Age-dependent effect of awareness during conditioning
6 Collaborators Human Eyeblink Conditioning Catherine Brawn Fortier (Boston Univ) Maria Carrillo (Rush Medical School) John Gabrieli (Stanford Univ) M-Grace Knuttinen (now at Univ Chicago) Regina McGlinchey-Berroth (Harvard Univ) Todd Parrish Alison Preston (Stanford Univ) Craig Weiss Supported By Lovibond & Shanks J Exp Psych: Animal Behav Processes vol.28, January 22 National Institute of Aging, National Institute of Mental Health, Bayer Corporation, and Parke-Davis Pharmaceuticals Knuttinen, Power, Preston & Disterhoft Behav Neurosci vol.115, August 21 Carrillo, Gabrieli, Hopkins, McGlinchey-Berroth, Fortier, Kesner, & Disterhoft Behav Neurosci vol.115, December 21
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