Executive Control Of Behavior Research Articles

Working Memory in People with Schizophrenia.

Working memory (WM) refers to the ability to maintain a small number of representations in an activated, easily accessible state for a short period of time in the service of ongoing cognitive processing and behavior. Because WM is a resource critical for multiple forms of complex cognition and executive control of behavior, it is of central interest in the study of disorders such as schizophrenia that involve a broad compromise of cognitive function and in the regulation of goal-directed behavior. There is now robust evidence that WM impairment is characteristic of people with schizophrenia. The impairment includes both elementary storage capacity as well as more complex forms of WM that involve the manipulation and updating of WM representations. These impairments appear to underlie a substantial portion of the generalized cognitive deficit in schizophrenia. Neuroimaging studies have implicated widespread abnormalities in the broad neural system that subserves WM performance, consistent with the evidence of broad cognitive impairment seen in PSZ.

Color-hierarchies in executive control of monkeys' behavior.

Processing advantages for particular colors (color-hierarchies) influence emotional regulation and cognitive functions in humans and manifest as an advantage of the red color, compared with the green color, in triggering response inhibition but not in response execution. It remains unknown how such color-hierarchies emerge in human cognition and whether they are the unique properties of human brain with advanced trichromatic vision. Dominant models propose that color-hierarchies are formed as experience-dependent learning that associates various colors with different human-made conventions and concepts (e.g., traffic lights). We hypothesized that if color-hierarchies modulate cognitive functions in trichromatic nonhuman primates, it would indicate a preserved neurobiological basis for such color-hierarchies. We trained six macaque monkeys to perform cognitive tasks that required behavioral control based on colored cues. Color-hierarchies significantly influenced monkeys' behavior and appeared as an advantage of the red color, compared to the green, in triggering response inhibition but not response execution. For all monkeys, the order of color-hierarchies, in response inhibition and also execution, was similar to that in humans. In addition, the cognitive effects of color-hierarchies were not limited to the trial in which the colored cues were encountered but also persisted in the following trials in which there was no colored cue on the visual scene. These findings suggest that color-hierarchies are not resulting from association of colors with human-made conventions and that simple processing advantage in retina or early visual pathways does not explain the cognitive effects of color-hierarchies. The discovery of color-hierarchies in cognitive repertoire of monkeys indicates that although the evolution of humans and monkeys diverged in about 25 million years ago, the color-hierarchies are evolutionary preserved, with the same order, in trichromatic primates and exert overarching effects on the executive control of behavior.

What Is the Evidence for Inter-laminar Integration in a Prefrontal Cortical Minicolumn?

The objective of this perspective article is to examine columnar inter-laminar integration during the executive control of behavior. The integration hypothesis posits that perceptual and behavioral signals are integrated within the prefrontal cortical inter-laminar microcircuits. Inter-laminar minicolumnar activity previously recorded from the dorsolateral prefrontal cortex (dlPFC) of nonhuman primates, trained in a visual delay match-to-sample (DMS) task, was re-assessed from an integrative perspective. Biomorphic multielectrode arrays (MEAs) played a unique role in the in vivo recording of columnar cell firing in the dlPFC layers 2/3 and 5/6. Several integrative aspects stem from these experiments: 1. Functional integration of perceptual and behavioral signals across cortical layers during executive control. The integrative effect of dlPFC minicolumns was shown by: (i) increased correlated firing on correct vs. error trials; (ii) decreased correlated firing when the number of non-matching images increased; and (iii) similar spatial firing preference across cortical-striatal cells during spatial-trials, and less on object-trials. 2. Causal relations to integration of cognitive signals by the minicolumnar turbo-engines. The inter-laminar integration between the perceptual and executive circuits was facilitated by stimulating the infra-granular layers with firing patterns obtained from supra-granular layers that enhanced spatial preference of percent correct performance on spatial trials. 3. Integration across hierarchical levels of the brain. The integration of intention signals (visual spatial, direction) with movement preparation (timing, velocity) in striatum and with the motor command and posture in midbrain is also discussed. These findings provide evidence for inter-laminar integration of executive control signals within brain’s prefrontal cortical microcircuits.

Interactive effects of music and prefrontal cortex stimulation in modulating response inhibition

Influential hypotheses propose that alterations in emotional state influence decision processes and executive control of behavior. Both music and transcranial direct current stimulation (tDCS) of prefrontal cortex affect emotional state, however interactive effects of music and tDCS on executive functions remain unknown. Learning to inhibit inappropriate responses is an important aspect of executive control which is guided by assessing the decision outcomes such as errors. We found that high-tempo music, but not low-tempo music or low-level noise, significantly influenced learning and implementation of inhibitory control. In addition, a brief period of tDCS over prefrontal cortex specifically interacted with high-tempo music and altered its effects on executive functions. Measuring event-related autonomic and arousal response of participants indicated that exposure to task demands and practice led to a decline in arousal response to the decision outcome and high-tempo music enhanced such practice-related processes. However, tDCS specifically moderated the high-tempo music effect on the arousal response to errors and concomitantly restored learning and improvement in executive functions. Here, we show that tDCS and music interactively influence the learning and implementation of inhibitory control. Our findings indicate that alterations in the arousal-emotional response to the decision outcome might underlie these interactive effects.

Interaction between Neural and Cardiac Systems during the Execution of the Stroop Task by Young Adults: Electroencephalographic Activity and Heart Rate Variability

Executive processes and heart rate variability (HRV) are supposedly regulated by an integrated inhibitory neurovisceral network mainly coordinated by the prefrontal cortex. Inhibitory control, a core executive function, is demanded by the Stroop task. This study aimed to assess the interaction between electroencephalographic activity and HRV of 50 healthy undergraduate students while performing a computerized version of the Stroop task with three stages (paradigmatic congruent – CS – and incongruent – IS – stages in addition to a stage in which words were phonetically similar to color names – PSS). Behavioral results suggested a Stroop interference effect among the stages, with greater difficulty in IS followed by PSS. A pattern of cortical activation in a frontoparietal gradient with left lateralization and involvement of the prefrontal, temporal and occipital cortices was found especially in IS and PSS, which might be correlated to executive control of behavior, inhibitory control, mental representation of words, preparation of the verbal response, and processing of visual stimuli. Mean power of brain activity (μV) was higher for IS and PSS for all tested frequency oscillations. HRV parameters of SDNN and pNN50 were smaller in PSS compared to the other stages, while rMSSD was higher for CS, suggesting higher mental stress for IS and PSS. During PSS, LF/HF ratio was negatively correlated with EEG power in frontal, central and temporal regions whilst rMSSD was positively correlated with activity in frontal and parietal regions. Therefore, marked prefrontal cortex activity was associated with parasympathetic dominance, which is in line with the integrated inhibitory neural network model. In summation, the execution of the Stroop task required increased recruitment of prefrontal cortical areas and led to high mental stress, but, as it was associated with parasympathetic dominance of HRV control, conflict was solved and subjects behaved successfully.

Direct current stimulation of prefrontal cortex modulates error-induced behavioral adjustments.

Commission of errors and conflict between choices might induce behavioral modulations through adjustments in the executive control of behavior and altered patterns of these modulations are detected in neuropsychiatric disorders. We examined the effects of transcranial Direct Current Stimulation (tDCS) applied over the dorsolateral prefrontal cortex (DLPFC) on error- and conflict-induced behavioral modulations. Two separate cohorts of participants performed two clinically relevant tests of executive control, respectively. In the Wisconsin Card Sorting Test (WCST), the relevant rule for matching items frequently changed and therefore participants had to detect these unannounced changes by trial and error and alter their rule-based behavior. In the Stop task, participants had to rapidly respond to a directional go-signal but inhibit their responses when a stop signal appeared after the go-signal. Each participant received tDCS (sham, cathodal or anodal) in three separate sessions. Errors led to a slower response in the next trial (post-error slowing) in both tasks. The tDCS significantly modulated the post-error slowing in both tasks but did not affect the behavioral adjustments induced by the conflict. The modulation of post-error slowing by tDCS were polarity-dependent and also trial specific appearing immediately after errors. In the WCST and Stop task, the post-error slowing may reflect different processes involved in shifting the behavior-guiding rule and adjustments in inhibitory control of responses, respectively, and we found that the effective tDCS polarity differed between the two tasks. Here, we show that in two separate cognitive tasks direct current stimulation of DLPFC significantly modulated error-induced behavioral modulations.

Disruption of columnar and laminar cognitive processing in primate prefrontal cortex following cocaine exposure.

Prefrontal cortical activity in primate brain plays a critical role in cognitive processes involving working memory and the executive control of behavior. Groups of prefrontal cortical neurons within specified cortical layers along cortical minicolumns differentially generate inter- and intra-laminar firing to process relevant information for goal oriented behavior. However, it is not yet understood how cocaine modulates such differential firing in prefrontal cortical layers. Rhesus macaque nonhuman primates (NHPs) were trained in a visual delayed match-to-sample (DMS) task while the activity of prefrontal cortical neurons (areas 46, 8 and 6) was recorded simultaneously with a custom multielectrode array in cell layers 2/3 and 5. Animals were reinforced with juice for correct responses. The first half of the recording session (control) was conducted following saline injection and in the second half of the same session cocaine was administered. Prefrontal neuron activity with respect to inter- and intra-laminar firing in layers 2/3 and 5 was assessed in the DMS task before and after the injection of cocaine. Results showed that firing rates of both pyramidal cells and interneurons increased on Match phase presentation and the Match Response (MR) in both control and cocaine halves of the session. Differential firing under cocaine vs. control in the Match phase was increased for interneurons but decreased for pyramidal cells. In addition, functional’ interactions between prefrontal pyramidal cells in layer 2/3 and 5 decreased while intra-laminar cross-correlations in both layers increased. These neural recordings demonstrate that prefrontal neurons differentially encode and process information within and between cortical cell layers via cortical columns which is disrupted in a differential manner by cocaine: administration.

Enhanced inhibitory control by neuropeptide Y Y5 receptor blockade in rats.

The neuropeptide Y (NPY) system acts in synergy with the classic neurotransmitters to regulate a large variety of functions including autonomic, affective, and cognitive processes. Research on the effects of NPY in the central nervous system has focused on food intake control and affective processes, but growing evidence of NPY involvement in attention-deficit/hyperactivity disorder (ADHD) and other psychiatric conditions motivated the present study. We tested the effects of the novel and highly selective NPY Y5 receptor antagonist Lu AE00654 on impulsivity and the underlying cortico-striatal circuitry in rats to further explore the possible involvement of the NPY system in pathologies characterized by inattention and impulsive behavior. A low dose of Lu AE00654 (0.03mg/kg) selectively facilitated response inhibition as measured by the stop-signal task, whereas no effects were found at higher doses (0.3 and 3mg/kg). Systemic administration of Lu AE00654 also enhanced the inhibitory influence of the dorsal frontal cortex on neurons in the caudate-putamen, this fronto-striatal circuitry being implicated in the executive control of behavior. Finally, by locally injecting a Y5 agonist, we observed reciprocal activation between dorsal frontal cortex and caudate-putamen neurons. Importantly, the effects of the Y5 agonist were attenuated by pretreatment with Lu AE00654, confirming the presence of Y5 binding sites modulating functional interactions within frontal-subcortical circuits. These results suggest that the NPY system modulates inhibitory neurotransmission in brain areas important for impulse control, and may be relevant for the treatment of pathologies such as ADHD and drug abuse.

Closing the loop in primate prefrontal cortex: inter-laminar processing

Prefrontal cortical (PFC) activity in the primate brain emerging from minicolumnar microcircuits plays a critical role in cognitive processes dealing with executive control of behavior. However, the specific operations of columnar laminar processing in prefrontal cortex (PFC) are not completely understood. Here we show via implementation of unique microanatomical recording and stimulating arrays, that minicolumns in PFC are involved in the executive control of behavior in rhesus macaque nonhuman primates (NHPs) performing a delayed-match-to-sample (DMS) task. PFC neurons demonstrate functional interactions between pairs of putative pyramidal cells within specified cortical layers via anatomically oriented minicolumns. Results reveal target-specific, spatially tuned firing between inter-laminar (layer 2/3 and layer 5) pairs of neurons participating in the gating of information during the decision making phase of the task with differential correlations between activity in layer 2/3 and layer 5 in the integration of spatial vs. object-specific information for correct task performance. Such inter-laminar processing was exploited by the interfacing of an online model which delivered stimulation to layer 5 locations in a pattern associated with successful performance thereby closing the columnar loop externally in a manner that mimicked normal processing in the same task. These unique technologies demonstrate that PFC neurons encode and process information via minicolumns which provides a closed loop form of “executive function,” hence disruption of such inter-laminar processing could form the bases for cognitive dysfunction in primate brain.

Neural substrates of contingency learning and executive control: dissociating physical, valuative, and behavioral changes

Contingency learning is fundamental to cognition. Knowledge about environmental contingencies allows behavioral flexibility, as executive control processes accommodate the demands of novel or changing environments. Studies of experiential learning have focused on the relationship between actions and the values of associated outcomes. However, outcome values have often been confounded with the physical changes in the outcomes themselves. Here, we dissociated contingency learning into valuative and non-valuative forms, using a novel version of the two-alternative choice task, while measuring the neural effects of contingency changes using functional magnetic resonance imaging (fMRI). Changes in value-relevant contingencies evoked activation in the lateral prefrontal cortex (LPFC), posterior parietal cortex (PPC), and dorsomedial prefrontal cortex (DMPFC) consistent with prior results (e.g., reversal-learning paradigms). Changes in physical contingencies unrelated to value or to action produced similar activations within the LPFC, indicating that LPFC may engage in generalized contingency learning that is not specific to valuation. In contrast, contingency changes that required behavioral shifts evoked activation localized to the DMPFC, supplementary motor, and precentral cortices, suggesting that these regions play more specific roles within the executive control of behavior.

Ethanol‐Induced Regulation of GABAA Subunit mRNAs in Prefrontal Fields of Cynomolgus Monkeys

Recent evidence indicates that functional impairment of the orbital and medial fields of the prefrontal cortex may underlie the deficits in executive control of behavior that characterize addictive disorders, including alcohol addiction. Moreover, previous studies have indicated that alcohol alters GABA neurotransmission and one substrate of these effects may be through the reconfiguration of the subunits constituting the GABA(A) receptor complex. Given that GABAergic transmission has an integral role in cortical processing, influencing local and interregional communication, understanding alcohol-induced alterations in GABA(A) receptors in prefrontal fields of the primate brain may provide insight into the functional impairment of these brain regions in the alcohol-addicted state and extend our understanding of the molecular consequences of long-term use in these critical brain regions. To address this problem, the effects of chronic ethanol self-administration in male cynomolgus monkeys on GABA(A) receptor subunit mRNA expression was studied in 3 frontal cortical fields: orbitofrontal cortex (OFC; area 13), anterior cingulate cortex (ACC; area 24), and the dorsolateral prefrontal cortex (DLPFC; area 46). Quantitative polymerase chain reaction revealed significant alterations in GABA(A) subunit mRNA expression in the OFC and DLPFC but not in the ACC. Specifically, expression of the alpha2, alpha4, beta1, beta3, and gamma1 to gamma3 subunit mRNAs was significantly less in the OFC, whereas the expression of beta1, beta2, gamma1, and delta subunit mRNAs was less in the DLPFC of alcohol-treated monkeys. These findings suggest that ethanol-induced alterations in GABA(A) function may be due to alterations in GABA(A) subunit mRNA levels and subunit-specific alterations are selective to particular cortical fields.

Directional Signals in the Prefrontal Cortex and in Area MT during a Working Memory for Visual Motion Task

Neurons in the middle temporal visual area (MT) have been implicated in the perception of visual motion, whereas prefrontal cortex (PFC) neurons have been linked to temporary storage of sensory signals, attentional and executive control of behavior. Using a task that placed demands on both sets of neurons, we investigated their contribution to working memory for visual motion. Monkeys compared the direction of two moving random-dot stimuli, sample and test, separated by a brief memory delay. Neurons in both areas showed robust direction-selective activity during all phases of the task. During the sample, approximately 60% of task-related PFC neurons were direction selective, and this selectivity emerged 40 ms later than in MT. Unlike MT, the PFC responses to sample did not correlate with behavioral choices, but their selectivity was modulated by task demands and diminished on error trials. Reliable directional signals were found in both areas during the memory delay, but these signals were transient rather than sustained by neurons of either area. Responses to the test in both areas were modulated by the remembered sample direction, decreasing when the test direction matched the sample. This decrease arose in the PFC 100 ms later than in MT and was predictive of the forthcoming decision. Our data suggest that neurons in the two regions are functionally connected and make unique contributions to different task components. PFC neurons reflect task-related information about visual motion and represent decisions that may be based, in part, on the comparison in MT between the remembered sample and test.

Activity in the Lateral Prefrontal Cortex Reflects Multiple Steps of Future Events in Action Plans

To achieve a behavioral goal in a complex environment, we must plan multiple steps of motor behavior. On planning a series of actions, we anticipate future events that will occur as a result of each action and mentally organize the temporal sequence of events. To investigate the involvement of the lateral prefrontal cortex (PFC) in such multistep planning, we examined neuronal activity in the PFC of monkeys performing a maze task that required the planning of stepwise cursor movements to reach a goal. During the preparatory period, PFC neurons reflected each of all forthcoming cursor movements, rather than arm movements. In contrast, in the primary motor cortex, most neuronal activity reflected arm movements but little of cursor movements during the preparatory period, as well as during movement execution. Our data suggest that the PFC is involved primarily in planning multiple future events that occur as a consequence of behavioral actions.

A topography of executive functions and their interactions revealed by functional magnetic resonance imaging

We used fMRI to study the brain processes involved in the executive control of behavior. The Sustained Attention to Response Task (SART), which allows unpredictable and predictable NOGO events to be contrasted, was imaged using a mixed (block and event-related) fMRI design to examine tonic and phasic processes involved in response inhibition, error detection, conflict monitoring and sustained attention. A network of regions, including right ventral prefrontal cortex (PFC), left dorsolateral PFC (DLPFC) and right inferior parietal cortex, was activated for successful unpredictable inhibitions, while rostral anterior cingulate was implicated in error processing and the pre-SMA in conflict monitoring. Furthermore, the pattern of correlations between left dorsolateral PFC, implicated in task-set maintenance, and the pre-SMA were indicative of a tight coupling between prefrontally mediated control and conflict levels monitored more posteriorly. The results reveal that the executive control of behavior can be separated into distinct functions performed by discrete cortical regions.