RATIONALE: Performance of cognitive tasks in nonhuman primates (NHPs) requires specific brain regions to make decisions under different degrees of difficulty or "cognitive load." OBJECTIVE: Local cerebral metabolic activity ([18F]FDG PET imaging) in dorsolateral prefrontal cortex (DLPFC), medial temporal lobe (MTL), and dorsal striatum (DStr) is examined in NHPs performing a delayed-match-to-sample (DMS) task with variable degrees of cognitive load. MATERIALS AND METHODS: Correlations between cognitive load and degree of brain metabolic activity were obtained with respect to the influence of the ampakine CX717 (Cortex Pharmaceuticals), using brain imaging and recordings of neuronal activity in NHPs and measures of intracellular calcium release in rat hippocampal slices. RESULTS: Activation of DLPFC, MTL, and DStr reflected changes in performance related to cognitive load within the DMS task and were engaged primarily on high load trials. Similar increased activation patterns and improved performance were also observed following administration of CX717. Sleep deprivation in NHPs produced impaired performance and reductions in brain activation which was reversed by CX717. One potential basis for this facilitation of cognition by CX717 was increased firing of task-specific hippocampal cells. Synaptic mechanisms affected by CX717 were examined in rat hippocampal slices which showed that N-methyl-D-aspartic acid-mediated release of intracellular calcium was reduced in slices from sleep-deprived rats and reversed by application of CX717 to the bathing medium. CONCLUSIONS: The findings provide insight into how cognition is enhanced by CX717 in terms of brain, and underlying neural, processes that are activated on high vs. low cognitive load trials.
RATIONALE: Performance of cognitive tasks in nonhuman primates (NHPs) requires specific brain regions to make decisions under different degrees of difficulty or "cognitive load." OBJECTIVE: Local cerebral metabolic activity ([18F]FDG PET imaging) in dorsolateral prefrontal cortex (DLPFC), medial temporal lobe (MTL), and dorsal striatum (DStr) is examined in NHPs performing a delayed-match-to-sample (DMS) task with variable degrees of cognitive load. MATERIALS AND METHODS: Correlations between cognitive load and degree of brain metabolic activity were obtained with respect to the influence of the ampakine CX717 (Cortex Pharmaceuticals), using brain imaging and recordings of neuronal activity in NHPs and measures of intracellular calcium release in rat hippocampal slices. RESULTS: Activation of DLPFC, MTL, and DStr reflected changes in performance related to cognitive load within the DMS task and were engaged primarily on high load trials. Similar increased activation patterns and improved performance were also observed following administration of CX717. Sleep deprivation in NHPs produced impaired performance and reductions in brain activation which was reversed by CX717. One potential basis for this facilitation of cognition by CX717 was increased firing of task-specific hippocampal cells. Synaptic mechanisms affected by CX717 were examined in rat hippocampal slices which showed that N-methyl-D-aspartic acid-mediated release of intracellular calcium was reduced in slices from sleep-deprived rats and reversed by application of CX717 to the bathing medium. CONCLUSIONS: The findings provide insight into how cognition is enhanced by CX717 in terms of brain, and underlying neural, processes that are activated on high vs. low cognitive load trials.
Authors: L Sokoloff; M Reivich; C Kennedy; M H Des Rosiers; C S Patlak; K D Pettigrew; O Sakurada; M Shinohara Journal: J Neurochem Date: 1977-05 Impact factor: 5.372
Authors: M Thomas; H Sing; G Belenky; H Holcomb; H Mayberg; R Dannals; H Wagner; D Thorne; K Popp; L Rowland; A Welsh; S Balwinski; D Redmond Journal: J Sleep Res Date: 2000-12 Impact factor: 3.981
Authors: Eric M Blalock; Richard Grondin; Kuey-chu Chen; Olivier Thibault; Veronique Thibault; Jignesh D Pandya; Amy Dowling; Zhiming Zhang; Patrick Sullivan; Nada M Porter; Philip W Landfield Journal: J Neurosci Date: 2010-04-28 Impact factor: 6.167
Authors: Robert E Hampson; Linda J Porrino; Ioan Opris; Terrence Stanford; Sam A Deadwyler Journal: Psychopharmacology (Berl) Date: 2010-09-24 Impact factor: 4.530
Authors: Ritchie E Brown; Radhika Basheer; James T McKenna; Robert E Strecker; Robert W McCarley Journal: Physiol Rev Date: 2012-07 Impact factor: 37.312
Authors: Sam A Deadwyler; Robert E Hampson; Dong Song; Ioan Opris; Greg A Gerhardt; Vasilis Z Marmarelis; Theodore W Berger Journal: Exp Neurol Date: 2016-05-24 Impact factor: 5.330
Authors: Robert E Hampson; Dong Song; Ioan Opris; Lucas M Santos; Dae C Shin; Greg A Gerhardt; Vasilis Z Marmarelis; Theodore W Berger; Sam A Deadwyler Journal: J Neural Eng Date: 2013-11-12 Impact factor: 5.379