Previously, studies using human neuroimaging and excitotoxic lesions in non-human primate have demonstrated an important role of ventrolateral prefrontal cortex (vlPFC) in higher order cognitive functions such as cognitive flexibility and the planning of behavioral sequences. In the present experiments, we tested effects on performance of temporary inactivation (using GABA receptor agonists) and dopamine (DA) D₂ and 5-HT_2A-receptor (R) blockade of vlPFC via local intracerebral infusions in the marmoset. We trained common marmosets to perform spatial self-ordered sequencing tasks in which one cohort of animals performed two and three response sequences on a continuously varying spatial array of response options on a touch-sensitive screen. Inactivation of vlPFC produced a marked disruption of accuracy of sequencing which also exhibited significant error perseveration. There were somewhat contrasting effects of D₂ and 5-HT_2A-R blockade, with the former producing error perseveration on incorrect trials, though not significantly impairing accuracy overall, and the latter significantly impairing accuracy but not error perseveration. A second cohort of marmosets were directly compared on performance of fixed versus variable spatial arrays. Inactivation of vlPFC again impaired self-ordered sequencing, but only with varying, and not fixed spatial arrays, the latter leading to the consistent use of fewer, preferred sequences. These findings add to evidence that vlPFC is implicated in goal-directed behavior that requires higher-order response heuristics that can be applied flexibly over different (variable), as compared with fixed stimulus exemplars. They also show that dopaminergic and serotonergic chemomodulation has distinctive effects on such performance.

SIGNIFICANCE STATEMENT This investigation employing local intracerebral infusions to inactivate the lateral prefrontal cortex (PFC) of the New World marmoset reveals the important role of this region in self-ordered response sequencing in variable but not fixed spatial arrays. These novel findings emphasize the higher order functions of this region, contributing to cognitive flexibility and planning of goal directed behavior. The investigation also reports for the first time somewhat contrasting neuromodulatory deficits produced by infusions of dopamine (DA) D₂ and 5-HT_2A receptor (R) antagonists into the same region, of possible significance for understanding cognitive deficits produced by anti-psychotic drugs.

以前，在非人类灵长类动物中使用人类神经影像学和兴奋毒性病变的研究已经证明腹外侧前额叶皮层 (vlPFC) 在高阶认知功能中的重要作用，例如认知灵活性和行为序列的规划。在本实验中，我们测试了对暂时失活（使用 GABA 受体激动剂）和多巴胺 (DA) D ₂和 5-HT _{2A 性能的影响}-受体 (R) 通过局部脑内注入狨猴阻断 vlPFC。我们训练了普通的狨猴来执行空间自序排序任务，其中一组动物在触摸屏上连续变化的响应选项空间阵列上执行两个和三个响应序列。vlPFC 的失活对测序的准确性产生了显着的破坏，这也表现出显着的错误持续存在。D ₂和 5-HT _2A有一些对比效果-R 封锁，前者在不正确的试验中产生错误持续性，尽管总体上不会显着损害准确性，而后者会显着损害准确性但不会导致错误持续性。第二组狨猴直接比较了固定与可变空间阵列的性能。vlPFC 的失活再次损害了自序排序，但仅适用于变化的而非固定的空间阵列，后者导致一致使用较少的首选序列。这些发现进一步证明，vlPFC 与目标导向行为有关，与固定刺激示例相比，该行为需要高阶响应启发式方法，可以灵活地应用于不同（变量）。他们还表明，多巴胺能和血清素能化学调节对这种表现有独特的影响。

意义声明本研究采用局部脑内灌注使新世界狨猴的外侧前额叶皮层 (PFC) 失活，揭示了该区域在可变但非固定空间阵列中自序反应排序中的重要作用。这些新发现强调了该区域的高阶功能，有助于认知灵活性和目标导向行为的规划。该调查还首次报告了将多巴胺 (DA) D ₂和 5-HT _2A受体 (R) 拮抗剂注入同一区域所产生的神经调节缺陷，这对理解抗精神病药物产生的认知缺陷可能具有重要意义.