Dose effects of triazolam on brain activity during episodic memory encoding: a PET study

Area of Science:

• Neuroscience
• Pharmacology
• Cognitive Psychology

Background:

• Benzodiazepines are known to impair episodic memory encoding.
• The specific neuroanatomical underpinnings of this impairment are not well understood.

Purpose of the Study:

• To investigate the acute dose effects of triazolam on brain activity during episodic memory encoding.
• To identify the neuroanatomical substrates of benzodiazepine-induced memory deficits.

Main Methods:

• Utilized positron emission tomography (PET) with 15O-H2O to measure regional cerebral blood flow (rCBF).
• Administered varying doses of triazolam (0.1, 0.2, 0.4 mg/70 kg) or placebo in a double-blind, within-subject design.
• Assessed brain activity during semantic and orthographic categorization tasks to isolate encoding-related rCBF.

Main Results:

• Replicated known prefrontal cortex activation during memory encoding in the placebo condition.
• Observed dose-related memory impairment and decreased activity in the right prefrontal cortex, left parahippocampal gyrus, and left anterior cingulate cortex with triazolam.
• Correlations indicated medial temporal lobe activation associated with subsequent memory performance.

Conclusions:

• Findings support the role of benzodiazepines in impairing prefrontal control and medial temporal lobe functions (contextual memory, episodic binding).
• Elucidates brain mechanisms of triazolam-induced memory deficits.
• Validates neuroimaging hypotheses about brain region functions in memory processes.