Functional significance of delay-period activity of primate prefrontal neurons in relation to spatial working memory and reward/omission-of-reward expectancy

The lateral prefrontal cortex (LPFC) is important in cognitive control. During the delay period of a working memory (WM) task, primate LPFC neurons show sustained activity that is related to retaining task-relevant cognitive information in WM. However, it has not yet been determined whether LPFC delay neurons are concerned exclusively with the cognitive control of WM task performance. Recent studies have indicated that LPFC neurons also show reward and/or omission-of-reward expectancy-related delay activity, while the functional relationship between WM-related and reward/omission-of-reward expectancy-related delay activity remains unclear. To clarify the functional significance of LPFC delay-period activity for WM task performance, and particularly the functional relationship between these two types of activity, we examined individual delay neurons in the primate LPFC during spatial WM (delayed response) and non-WM (reward–no-reward delayed reaction) tasks. We found significant interactions between these two types of delay activity. The majority of the reward expectancy-related neurons and the minority of the omission-of-reward expectancy-related neurons were involved in spatial WM processes. Spatial WM-related neurons were more likely to be involved in reward expectancy than in omission-of-reward expectancy. In addition, LPFC delay neurons observed during the delayed response task were not concerned exclusively with the cognitive control of task performance; some were related to reward/omission-of-reward expectancy but not to WM, and many showed more memory-related activity for preferred rewards than for less-desirable rewards. Since employing a more preferred reward induced better task performance in the monkeys, as well as enhanced WM-related neuronal activity in the LPFC, the principal function of the LPFC appears to be the integration of cognitive and motivational operations in guiding the organism to obtain a reward more effectively.     

Movement-related activity of thalamic neurons with input from the globus pallidus and projection to the motor cortex in the monkey

Summary Thalamic neurons projecting to the arm area of the motor cortex were identified by their antidromic response to stimulation of that area in two awake monkeys. Neurons were further identified as receiving inputs from the cerebellar nuclei or the internal segment of the globus pallidus by excitatory or inhibitory response to stimulation of these nuclei. Most (33/34) of the thalamic neurons in the cerebello-thalamo-cortical projection and more than half (12/18) of those in the pallido-thalamocortical projection changed their firing rate on the leverlifting hand movement in the reaction-time task. A considerable number of neurons of both groups (14/23 and 3/10) changed their firing rate prior to the onset of the earliest EMG. These findings agree with the model that activities of pallidal as well as cerebellar nuclear neurons related to motor control are transmitted to the motor cortex through the thalamus.     

Globus Pallidus and motor initiation: the bilateral effects of unilateral quisqualic acid-induced lesion on reaction times in monkeys

The results of many experimental studies have shown that the globus pallidus (GP) is involved in the control of motor activities, particularly during motor execution. Whether or not the GP is involved in the initiation phase is still a matter of controversy, however. This question was investigated in the present study in Papio papio monkeys after GP lesion using a simple reaction time (RT) task, focusing particularly on the initiation phase. The monkeys were trained to perform this task, which consisted of raising their hand as quickly as possible in response to a visual signal. The RT and its premotor and motor components were measured. In addition, the distribution of the RTs was analyzed in order to assess the number of long latency responses. After making unilateral GP cell lesions by locally injecting small amounts of the excitatory amino acid quisqualic acid, a bilateral increase was observed in RT. This lengthening involved both the premotor and the motor phases of the RT when the task was performed with the contralateral limb and only the premotor phase when it was performed with the ipsilateral one. A significant increase was observed in the percentage of long latency responses recorded in the contralateral limb after the GP lesion but not in the ipsilateral one. Increases in the RT and in the percentage of long latency responses are thought to constitute two indices of the akinesia observed in our task involving speed constraints, which suggests that the GP may participate in motor initiation. A complete recovery of the RT was observed within one month, whereas the increase in the percentage of long latency responses persisted. These two indices of akinesia seemed therefore to result from an impairment involving both motor and nonmotor processes. These data suggest that the GP may be involved in the control of postural adjustment, motivation, and/or the control of the initial isometric part of movements. The time course of the recovery from the deficits observed after GP lesion shows the existence of mechanisms which seem to have been operative particularly in the case of impairments affecting motor processes.     

Postsynaptic alpha-2 receptor stimulation improves memory in aged monkeys: Indirect effects of yohimbine versus direct effects of clonidine

Very low doses (0.00001 mg/kg) of the alpha-2 adrenergic antagonist, yohimbine, improved working memory performance in a subset of aged monkeys. Improvement appeared to result from increased norepinephrine (NE) release onto postsynaptic alpha-2 adrenoceptors, as the response was blocked by the “postsynaptic” alpha-2 antagonist, SKF104078. Cognitive-enhancing effects of low dose yohimbine treatment may depend on aged animals retaining an intact, endogenous NE system. In contrast to yohimbine, the alpha-2 agonist, clonidine, has improved working memory in all aged animals examined. In the present study, clonidine's beneficial effects were also blocked by the postsynaptic antagonists SKF104078 and SKF104856, suggesting that clonidine acts by directly stimulating postsynaptic alpha-2 adrenoceptors. Beneficial doses of clonidine (0.01 mg/kg) and yohimbine (0.00001 mg/kg) were combined to see if they would produce additive effects on memory enhancement. This strategy was successful in young monkeys with intact NE systems but was not effective in the aged monkeys. These findings demonstrate that drugs that indirectly stimulate postsynaptic alpha-2 receptors by increasing NE release are not as reliable in aged monkeys as directly acting agonists that can replace NE at postsynaptic alpha-2 receptors.     

Facts and Artifacts in Cardiac Cycle Time Analysis: A Simple Model of Vagal Control

Cardiac cycle time effects occur when stimuli or responses presented at different times within the cardiac cycle induce differential changes in the same or following interbeat interval (IBI). Two related problems regarding cardiac cycle time effects are discussed. One problem concerns how to separate anticipatory from stimulus-induced changes in interbeat intervals that occur around the time of presentation of an expected stimulus. The other problem is an anomalous finding in reaction time tasks: prestimulus interbeat intervals are longer when they precede stimuli presented early, rather than late, in the cardiac cycle. These two problems can be understood if some simple assumptions are made about anticipatory and stimulus-induced vagal excitation. If vagal excitation regularly increases prior to an expected event, the anomalous effect of stimulus delay in the cardiac cycle on preceding interbeat intervals can be explained. The presentation of events and IBI times on an ordinal IBI axis induces an inappropriate time shift. Furthermore, estimates of maximal anticipatory deceleration at stimulus onset in the interbeat interval of the stimulus and of subsequent stimulus-induced vagal changes can be inferred. The relevance of this analysis to earlier experimental results is discussed.