Effects of cocaine rewards on neural representations of cognitive demand in nonhuman primates

Abstract

Rationale Investigations of the neural consequences of the effects of cocaine on cognition have centered on specific brain circuits including prefrontal cortex, medial temporal lobe and striatum and their roles in controlling drug dependent behavior and addiction. These regions are critical to many aspects of drug abuse; however recent investigations in addicted individuals have reported possible cognitive deficits that impact recovery and other therapeutic interventions. Objectives Therefore a direct assessment of the effects of cocaine as a reward for cognitive function provides a means of determining how brain systems involved such as prefrontal cortex are affected under normal vs. conditions of acute drug exposure as a precursor to the final impaired function in the addicted state. Methods Nonhuman primates (NHPs) were tested in a delayed-match-to-sample decision making task to determine effects of high vs. low cognitive load trials on single neuron activity and fluorodeoxyglucose-positron emission tomography (FDG-PET) determined metabolic activation of prefrontal cortex when juice vs. intravenous cocaine were employed as rewards for successful performance. Results Cognitive processing in prefrontal cortex was altered primarily on high load trials in which cocaine was randomly presented as the signaled and delivered reward on particular trials. The detrimental actions of cocaine rewards were also shown to persist and impair task performance on subsequent juice rewarded trials. Conclusions The findings indicate that one of the ways in which cocaine use may disrupt performance of a cognitive task is to alter neural processing in prefrontal cortex when involved in discriminating circumstances on the basis of low vs. high cognitive demand.

Columnar Processing in Primate pFC: Evidence for Executive Control Microcircuits

“…Nonhuman primates (NHPs) utilized as subjects in this study ( n = 4) were trained for at least 2 years to perform a well characterized, custom-designed visual DMS task (Hampson, Porrino, Opris, Stanford, & Deadwyler, 2011; Opris et al, 2011) shown in Figure 1A. Animals were seated in a primate chair with a shelf-counter in front of a display screen (Figure 1A) during performance of the task.…”

“…During surgery animals were anesthetized with ketamine (10 mg/kg), then intubated and maintained with isoflurane (1–2% in oxygen 6 l/min). Recording cylinders (Crist Instruments, Hagerstown, MD) were placed over 20-mm diameter craniotomies for electrode access (Hampson et al, 2011) to stereotaxic coordinates of the frontal cortex (25 mm anterior relative to interaural line and 12 mm lateral to midline/vertex) in the caudal region of the principal sulcus, the dorsal limb of arcuate sulcus in area 8 and the dorsal part of premotor area 6 (Figure 1C, D), areas previously shown by PET imaging to become activated during task performance (Figure 1E; Hampson et al, 2011). Two titanium posts were secured to the skull for head restraint with titanium steel screws embedded in bone cement.…”

A novel tetrode microdrive for simultaneous multi-neuron recording from different regions of primate brain

“…Testing with the microdrive device was performed on 4 adult (rhesus, Macaca mulatta) NHPs used in other studies (Opris et al 2009, Hampson et al, 2011). As shown in Figure 3 (middle) prior placement of bilateral skull recording chambers in each animal provided access to motor cortex, hippocampus, and striatum in one hemisphere or different layers of prefrontal cortex (PFC) in the other hemisphere (Hampson et al, 2004; Opris et al, 2010).…”

“…As demonstrated here, a new uniquely designed tetrode-microdrive device was successfully constructed and tested (Santos et al, 2010) in well established neurobehavioral contexts (Hampson et al, 2004; Hampson et al, 2011; Opris et al, 2009) to accomplish these objectives. The device provides the means to access neural firing in specific regions identified in imaging procedures (Porrino et al, 2005) without constraints due to positioning, depth of structure or number of loci within specific brain areas.…”

“…The device provides the means to access neural firing in specific regions identified in imaging procedures (Porrino et al, 2005) without constraints due to positioning, depth of structure or number of loci within specific brain areas. We show here data obtained with the device in single sessions consisting of relatively large numbers of well-isolated single neurons (n=20–50) recorded simultaneously from multiple cortical as well as multiple subcortical regions while NHPs performed a visuomotor short-term memory task (Hampson et al 2004, Hampson et al 2011). This innovative technology provides a basis for advanced understanding of neural systems in the human brain in which task-related activity of multiple neuron populations in cortical regions can now be related to previously unobtainable simultaneous multiple subcortical recordings of the same type.…”