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Conclusions from PET Studies

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  1. Conclusions from PET Studies • Schizophrenia is not a disease of a single brain region • Areas of abnormality vary depending on the task and the nature of current symptoms • Schizophrenia affects distributed circuitry throughout the brain

  2. fMR Studies The fastest-growing field in neuroimaging

  3. The fMR Blood Flow Signal

  4. Verbal Fluency Patients Controls

  5. The N-Back Task for fMR Experimental Task (2-Back): Remember the Probe and Monitor for It Comparison Task: Look for the S Look for the S 2-Back Task L A Probe x B G C Target x S K D Target E A

  6. 2-Back Task in Normals • Bilateral dorsolateral frontal • Bilateral parietal • Anterior cingulate

  7. 2-Back Task in Schizophrenia (unmedicated) • Blood flow markedly decreased or absent in regions used by normals • Main activation is anterior cingulate

  8. NeuropsychologyCognitive PsychologyCognitive Neuroscience

  9. Classical Neuropsychology • Derived from the study of neurology patients with specific brain lesions • Develops tests that are sensitive to detecting those lesions • Pattern of test performance used to determine the site of the lesion

  10. Cognitive Neuropsychology/ Neuroscience • Emphasizes cognitive processes rather than test performance or lesion location • Seeks to find dissociations between types of cognitive processes (e.g., episodic vs semantic memory) • Assumes that mental processes are based on fundamental cognitive “modules” that will map onto discrete brain systems

  11. Methodological Issues • Absence of any specific lesion in schizophrenia • Effects of medication on test performance • Effects of institutionalization • Effects of envirnomental stimuli or distractors

  12. Generalized Deficits in Schizophrenia • Patients perform poorly on almost all cognitive tests • Evidence to date does not support a lesion in a specific brain region (neuropsychology) or an impairment in a specific cognitive system (cognitive neuroscience)

  13. Cognitive Studies: Faculties • Attention • Memory • Language • Executive function • Very little evidence supports a specific dysfunction in attention, memory, or language in schizophrenia—all are impaired • These specific cognitive faculties could be impaired due to a problem in executive function

  14. Lobology: Evidence from Cognitive Tests • Occipital: little evidence • Parietal: some evidence • Temporal: more evidence • Frontal: even more evidence • However…these inferences are based on the (potentially inapplicable) assumptions of neuropsychological lesion studies

  15. Models of Signs and Symptoms: Cognitive Neuropsychiatry • Attempts to explain signs and symptoms, rather than schizophrenia in general • E.g., negative symptoms, positive symptoms, social interactions

  16. Negative Symptoms • Poverty of speech, affective blunting, motor retardation share a common feature—lack of spontaneous behavior or “willed action” • Could be explained on the basis of abnormalities in the fronto-striatal “functional loop”

  17. Hallucinations • Multiple cognitive explanations, such as… • The experience of inner speech as alien or exterior • Due to a failure in self-monitoring, so that speech or thoughts occur without awareness of prior intention, and are therefore perceived as alien

  18. Persecutory Delusions • Result from the patient making incorrect inferences about the intentions of others or the meaning of stimuli in the external environment • Due to a failure of the ability to infer the beliefs or intentions of others (“theory of mind” or “mentalizing”)

  19. Modern Cognitive Models • A disease with no consistent neuropathology • A disease that arises from dysfunctional neural circuits (no obvious lesion) • A disease that is defined by cognitive impairment

  20. Some Modern Cognitive Models • Working memory/ representationally guided behavior • Information processing/sensory gating • Synchrony of thought/cognitive dysmetria

  21. Working Memory • The ability to hold information online and perform mental operations using it • Permits individuals to base behavior on internally held plans rather than being driven by external stimuli • Can explain most symptoms—e.g., the inability to correctly reference sensory experiences could lead to delusions and hallucinations • Is supported by multiple imaging and cognitive studies

  22. Sensory Gating • A problem in filtering or gating information • Leads to the subject experience of being bombarded by stimuli • Explains most symptoms—e.g., confusion of internal and external stimuli would cause delusions and hallucinations • Supported by neurophysiological studies of prepulse inhibition

  23. Cognitive Dysmetria • A defect in coordinating mental activity • Due to disturbed functional connectivity between the cortex and subcortical regions (thalamus and cerebellum) • Leads to functional and cognitive misconnections • Explains diversity of symptoms (e.g., misconnecting a perception and its meaning might lead to delusions and hallucinations) • Supported by functional imaging studies