Acute effects of cocaine on the neurobiology of cognitive control

Compromised ability to exert control over drug urges and drug-seeking behaviour is a characteristic of addiction. One specific cognitive control function, impulse control, has been shown to be a risk factor for the development of substance problems and has been linked in animal models to increased drug administration and relapse. We present evidence of a direct effect of cocaine on the neurobiology underlying impulse control. In a laboratory test of motor response inhibition, an intravenous cocaine administration improved task performance in 13 cocaine users. This improvement was accompanied by increased activation in right dorsolateral and inferior frontal cortex, regions considered critical for this cognitive function. Similarly, for both inhibitory control and action monitoring processes, cocaine normalized activation levels in lateral and medial prefrontal regions previously reported to be hypoactive in users relative to drug-naive controls. The acute amelioration of neurocognitive dysfunction may reflect a chronic dysregulation of those brain regions and the cognitive processes they subserve. Furthermore, the effects of cocaine on midline function suggest a dopaminergically mediated intersection between cocaine's acute reinforcing effects and its effects on cognitive control.     

Levels of integration in cognitive control and sequence processing in the prefrontal cortex

Cognitive control is necessary to flexibly act in changing environments. Sequence processing is needed in language comprehension to build the syntactic structure in sentences. Functional imaging studies suggest that sequence processing engages the left ventrolateral prefrontal cortex (PFC). In contrast, cognitive control processes additionally recruit bilateral rostral lateral PFC regions. The present study aimed to investigate these two types of processes in one experimental paradigm. Sequence processing was manipulated using two different sequencing rules varying in complexity. Cognitive control was varied with different cue-sets that determined the choice of a sequencing rule. Univariate analyses revealed distinct PFC regions for the two types of processing (i.e. sequence processing: left ventrolateral PFC and cognitive control processing: bilateral dorsolateral and rostral PFC). Moreover, in a common brain network (including left lateral PFC and intraparietal sulcus) no interaction between sequence and cognitive control processing was observed. In contrast, a multivariate pattern analysis revealed an interaction of sequence and cognitive control processing, such that voxels in left lateral PFC and parietal cortex showed different tuning functions for tasks involving different sequencing and cognitive control demands. These results suggest that the difference between the process of rule selection (i.e. cognitive control) and the process of rule-based sequencing (i.e. sequence processing) find their neuronal underpinnings in distinct activation patterns in lateral PFC. Moreover, the combination of rule selection and rule sequencing can shape the response of neurons in lateral PFC and parietal cortex.     

Immature frontal lobe contributions to cognitive control in children: evidence from fMRI.

Event-related fMRI was employed to characterize differences in brain activation between children ages 8-12 and adults related to two forms of cognitive control: interference suppression and response inhibition. Children were more susceptible to interference and less able to inhibit inappropriate responses than were adults. Effective interference suppression in children was associated with prefrontal activation in the opposite hemisphere relative to adults. In contrast, effective response inhibition in children was associated with activation of posterior, but not prefrontal, regions activated by adults. Children failed to activate a region in right ventrolateral prefrontal cortex that was recruited for both types of cognitive control by adults. Thus, children exhibited immature prefrontal activation that varied according to the type of cognitive control required.     

The neural bases of cognitive conflict and control in moral judgment

Traditional theories of moral psychology emphasize reasoning and "higher cognition," while more recent work emphasizes the role of emotion. The present fMRI data support a theory of moral judgment according to which both "cognitive" and emotional processes play crucial and sometimes mutually competitive roles. The present results indicate that brain regions associated with abstract reasoning and cognitive control (including dorsolateral prefrontal cortex and anterior cingulate cortex) are recruited to resolve difficult personal moral dilemmas in which utilitarian values require "personal" moral violations, violations that have previously been associated with increased activity in emotion-related brain regions. Several regions of frontal and parietal cortex predict intertrial differences in moral judgment behavior, exhibiting greater activity for utilitarian judgments. We speculate that the controversy surrounding utilitarian moral philosophy reflects an underlying tension between competing subsystems in the brain.     

Neurodevelopmental changes in working memory and cognitive control

One of the most salient ways in which our behavior changes during childhood and adolescence is that we get better at working towards long-term goals, at ignoring irrelevant information that could distract us from our goals, and at controlling our impulses - in other words, we exhibit improvements in cognitive control. Several recent magnetic resonance imaging studies have examined the developmental changes in brain structure and function that underlie improvements in working memory and cognitive control. Increased recruitment of task-relevant regions in the prefrontal cortex, parietal cortex and striatum over the course of development is associated with better performance in a range of cognitive tasks. Further work is needed to assess the role of experience in shaping the neural circuitry that underlies cognitive control.     

Cognitive control in adolescence: neural underpinnings and relation to self-report behaviors

Background

Adolescence is commonly characterized by impulsivity, poor decision-making, and lack of foresight. However, the developmental neural underpinnings of these characteristics are not well established.

Methodology/Principal Findings

To test the hypothesis that these adolescent behaviors are linked to under-developed proactive control mechanisms, the present study employed a hybrid block/event-related functional Magnetic Resonance Imaging (fMRI) Stroop paradigm combined with self-report questionnaires in a large sample of adolescents and adults, ranging in age from 14 to 25. Compared to adults, adolescents under-activated a set of brain regions implicated in proactive top-down control across task blocks comprised of difficult and easy trials. Moreover, the magnitude of lateral prefrontal activity in adolescents predicted self-report measures of impulse control, foresight, and resistance to peer pressure. Consistent with reactive compensatory mechanisms to reduced proactive control, older adolescents exhibited elevated transient activity in regions implicated in response-related interference resolution.

Conclusions/Significance

Collectively, these results suggest that maturation of cognitive control may be partly mediated by earlier development of neural systems supporting reactive control and delayed development of systems supporting proactive control. Importantly, the development of these mechanisms is associated with cognitive control in real-life behaviors.     

Quantifying the Reconfiguration of Intrinsic Networks during Working Memory

Rapid, flexible reconfiguration of connections across brain regions is thought to underlie successful cognitive control. Two intrinsic networks in particular, the cingulo-opercular (CO) and fronto-parietal (FP), are thought to underlie two operations critical for cognitive control: task-set maintenance/tonic alertness and adaptive, trial-by-trial updating. Using functional magnetic resonance imaging, we directly tested whether the functional connectivity of the CO and FP networks was related to cognitive demands and behavior. We focused on working memory because of evidence that during working memory tasks the entire brain becomes more integrated. When specifically probing the CO and FP cognitive control networks, we found that individual regions of both intrinsic networks were active during working memory and, as expected, integration across the two networks increased during task blocks that required cognitive control. Crucially, increased integration between each of the cognitive control networks and a task-related, non-cognitive control network (the hand somatosensory-motor network; SM) was related to increased accuracy. This implies that dynamic reconfiguration of the CO and FP networks so as to increase their inter-network communication underlies successful working memory.     

Neural mechanisms of transient and sustained cognitive control during task switching

A hybrid blocked and event-related functional magnetic resonance imaging (fMRI) study decomposed brain activity during task switching into sustained and transient components. Contrasting task-switching blocks against single-task blocks revealed sustained activation in right anterior prefrontal cortex (PFC). Contrasting task-switch trials against task-repeat and single-task trials revealed activation in left lateral PFC and left superior parietal cortex. In both sets of regions, activation dynamics were strongly modulated by trial-by-trial fluctuations in response speed. In addition, right anterior PFC activity selectively covaried with the magnitude of mixing cost (i.e., task-repeat versus single-task trial performance), and left superior parietal activity selectively covaried with the magnitude of the switching cost (i.e., task-switch versus task-repeat trial performance). These results indicate a functional double dissociation in brain regions supporting different components of cognitive control during task switching and suggest that both sustained and transient control processes mediate the behavioral performance costs of task switching.     

Training attentional control in infancy

Several recent studies have reported that cognitive training in adults does not lead to generalized performance improvements [1, 2], whereas many studies with younger participants (children 4 years and older) have reported distal transfer [3, 4]. This is consistent with convergent evidence [5-8] for greater neural and behavioral plasticity earlier in development. We used gaze-contingent paradigms to train 11-month-old infants on a battery of attentional control tasks. Relative to an active control group, and following only a relatively short training period, posttraining assessments revealed improvements in cognitive control and sustained attention, reduced saccadic reaction times, and reduced latencies to disengage visual attention. Trend changes were also observed in spontaneous looking behavior during free play, but no change was found in working memory. The amount of training correlated with the degree of improvement on some measures. These findings are to our knowledge the first demonstration of distal transfer following attentional control training in infancy. Given the longitudinal relationships identified between early attentional control and learning in academic settings [9, 10], and the causal role that impaired control of attention may play in disrupting learning in several disorders [11-14], the current results open a number of avenues for future work.     

Prefrontal cortex guides context-appropriate responding during language production

Although language processing is thought to frequently require cognitive control, little is known about the cognitive and neural basis of the control of language. Here, we demonstrate that processing of context by the PFC plays an important role in the control of language comprehension and production. Using a missing letter paradigm and fMRI, we found that increased activation in the PFC (but not in posterior regions), while encoding and maintaining context information, predicted context-appropriate responses. Furthermore, greater selection demands increased activity during responding in the same regions engaged during the encoding and maintenance of context. Overall, as in other cognitive task domains, these results suggest that PFC context processing plays an important role in the control of language.     

The prefrontal cortex and cognitive control

One of the enduring mysteries of brain function concerns the process of cognitive control. How does complex and seemingly willful behaviour emerge from interactions between millions of neurons? This has long been suspected to depend on the prefrontal cortex--the neocortex at the anterior end of the brain--but now we are beginning to uncover its neural basis. Nearly all intended behaviour is learned and so depends on a cognitive system that can acquire and implement the 'rules of the game' needed to achieve a given goal in a given situation. Studies indicate that the prefrontal cortex is central in this process. It provides an infrastructure for synthesizing a diverse range of information that lays the foundation for the complex forms of behaviour observed in primates.     

Precision grasping in humans: from motor control to cognition

In the past decade, functional neuroimaging has proved extremely useful in mapping the human motor circuits involved in skilled hand movements. However, one major drawback of this approach is the impossibility to determine the exact contribution of each individual cortical area to precision grasping. Because transcranial magnetic stimulation (TMS) makes it possible to induce a transient 'virtual' lesion of discrete brain regions in healthy subjects, it has been extensively used to provide direct insight into the causal role of a given area in human motor behaviour. Recent TMS studies have allowed us to determine the specific contribution, as well as the timing and the hemispheric lateralisation, of distinct parietal and frontal areas to the control of both the kinematics and dynamics of precision grasping. Moreover, recent researches have shown that the same cortical network may contribute to language and number processing, supporting the existence of tight interactions between processes involved in cognition and actions. The aim of this paper is to offer a concise overview of recent studies that have investigated the neural correlates of precision grasping and the possible contribution of the motor system to higher cognitive functions such as language and number processing.     

Reward Sensitivity Modulates Brain Activity in the Prefrontal Cortex,ACC and Striatum during Task Switching

Current perspectives on cognitive control acknowledge that individual differences in motivational dispositions may modulate cognitive processes in the absence of reward contingencies. This work aimed to study the relationship between individual differences in Behavioral Activation System (BAS) sensitivity and the neural underpinnings involved in processing a switching cue in a task-switching paradigm. BAS sensitivity was hypothesized to modulate brain activity in frontal regions, ACC and the striatum. Twenty-eight healthy participants underwent fMRI while performing a switching task, which elicited activity in fronto-striatal regions during the processing of the switch cue. BAS sensitivity was negatively associated with activity in the lateral prefrontal cortex, anterior cingulate cortex and the ventral striatum. Combined with previous results, our data indicate that BAS sensitivity modulates the neurocognitive processes involved in task switching in a complex manner depending on task demands. Therefore, individual differences in motivational dispositions may influence cognitive processing in the absence of reward contingencies.     

The effects of environmental control on cognition in rats (Rattus norvegicus)

The aim of this study was to allow nonhuman animals to control their environment using operant conditioning procedures and to assess the effect of control on cognitive tasks. The study tested 4 predictions: (a) rats (Rattus norvegicus) will control a light stimulus; (b) animals will exhibit preferences for particular stimulus strengths; (c) animals who exert control over environmental stimuli will show improved performance on cognitive tasks compared with animals who lack control; and (d) at the end of the operant phase, experimental subjects will have lower corticosterone levels than animals who lack control. Experimental subjects did show control over a light stimulus and performed significantly better over time in a discrimination task compared with subjects who could not control their environment. There was no difference in corticosterone levels between control and experimental subjects. The results will both contribute to our understanding of how control of environmental stimuli affects the welfare of animals in captive environments and aid in designing experimental conditions that will increase validity and reliability in research.     

Peculiarities of changes of EEG reactivity during performance of dual tasks in healthy subjects (voluntary postural control and calculation)

Complex EEG and stabilography investigation with separate and simultaneous performance of motor (voluntary postural control) and cognitive (calculation) tasks has been performed in 20 healthy subjects (22 +/- 0.7 yo.). Specific spatial and frequency reactive changes have been revealed during motor task performance. These included increase of coherence in alpha-band for long pair of channels in right hemisphere as well as in symmetric parietal-occipital regions in both hemispheres. Cognitive task performance has been accompanied by coherence increase for low bands (delta- and theta-) with higher activation in left hemisphere and frontal regions. In dual tasks where both components were performed worse comparing to control, performance led to reactive spatial and frequency changes of both--motor and cognitive--tasks, though these changes were less than during separate task performance. Decrease of coherence in alphal-band in frontal areas appeared as a zone of "conflict of interest - interferention". In dual tasks with better performance of each component comparing to control EEG coherence increased in each specific area as well as in areas of "conflict of interest".     

Modality-specific control of strategic spatial attention in parietal cortex

The neural basis of selective spatial attention presents a significant challenge to cognitive neuroscience. Recent neuroimaging studies have suggested that regions of the parietal and temporal cortex constitute a "supramodal" network that mediates goal-directed attention in multiple sensory modalities. Here we used transcranial magnetic stimulation (TMS) to determine which cortical subregions control strategic attention in vision and touch. Healthy observers undertook an orienting task in which a central arrow cue predicted the location of a subsequent visual or somatosensory target. To determine the attentional role of cortical subregions at different stages of processing, TMS was delivered to the right hemisphere during cue or target events. Results indicated a critical role of the inferior parietal cortex in strategic orienting to visual events, but not to somatosensory events. These findings are inconsistent with the existence of a supramodal attentional network and instead provide direct evidence for modality-specific attentional processing in parietal cortex.     

Network-Level Structural Abnormalities of Cerebral Cortex in Type 1 Diabetes Mellitus

Type 1 diabetes mellitus (T1DM) usually begins in childhood and adolescence and causes lifelong damage to several major organs including the brain. Despite increasing evidence of T1DM-induced structural deficits in cortical regions implicated in higher cognitive and emotional functions, little is known whether and how the structural connectivity between these regions is altered in the T1DM brain. Using inter-regional covariance of cortical thickness measurements from high-resolution T1-weighted magnetic resonance data, we examined the topological organizations of cortical structural networks in 81 T1DM patients and 38 healthy subjects. We found a relative absence of hierarchically high-level hubs in the prefrontal lobe of T1DM patients, which suggests ineffective top-down control of the prefrontal cortex in T1DM. Furthermore, inter-network connections between the strategic/executive control system and systems subserving other cortical functions including language and mnemonic/emotional processing were also less integrated in T1DM patients than in healthy individuals. The current results provide structural evidence for T1DM-related dysfunctional cortical organization, which specifically underlie the top-down cognitive control of language, memory, and emotion.     

Divergent neural substrates of inhibitory control in binge eating disorder relative to other manifestations of obesity

Objective:

An important endeavor involves increasing our understanding of biobehavioral processes underlying different types of obesity. The current study investigated the neural correlates of cognitive control (involving conflict monitoring and response inhibition) in obese individuals with binge eating disorder (BED) as compared to BMI‐matched non‐BED obese (OB) individuals and lean comparison (LC) participants. Alterations in cognitive control may contribute to differences in behavioral control over eating behaviors in BED and obesity.

Design and Methods:

Participants underwent functional magnetic resonance imaging while completing the Stroop color‐word interference task.

Results and Conclusions:

Relative to the OB and LC groups, activity in the BED group was differentiated by relative hypoactivity in brain areas involved in self‐regulation and impulse control. Specifically, the BED group showed diminished activity in the ventromedial prefrontal cortex (vmPFC), inferior frontal gyrus (IFG), and insula during Stroop performance. In addition, dietary restraint scores were negatively correlated with right IFG and vmPFC activation in the BED group, but not in the OB or HC groups. Thus, BED individuals' diminished ability to recruit impulse‐control‐related brain regions appears associated with impaired dietary restraint. The observed differences in neural correlates of inhibitory processing in BED relative to OB and LC groups suggest distinct eurobiological contributions to binge eating as a subgroup of obese individuals.     

Altered Regional and Circuit Resting-State Activity Associated with Unilateral Hearing Loss

The deprivation of sensory input after hearing damage results in functional reorganization of the brain including cross-modal plasticity in the sensory cortex and changes in cognitive processing. However, it remains unclear whether partial deprivation from unilateral auditory loss (UHL) would similarly affect the neural circuitry of cognitive processes in addition to the functional organization of sensory cortex. Here, we used resting-state functional magnetic resonance imaging to investigate intrinsic activity in 34 participants with UHL from acoustic neuroma in comparison with 22 matched normal controls. In sensory regions, we found decreased regional homogeneity (ReHo) in the bilateral calcarine cortices in UHL. However, there was an increase of ReHo in the right anterior insular cortex (rAI), the key node of cognitive control network (CCN) and multimodal sensory integration, as well as in the left parahippocampal cortex (lPHC), a key node in the default mode network (DMN). Moreover, seed-based resting–state functional connectivity analysis showed an enhanced relationship between rAI and several key regions of the DMN. Meanwhile, lPHC showed more negative relationship with components in the CCN and greater positive relationship in the DMN. Such reorganizations of functional connectivity within the DMN and between the DMN and CCN were confirmed by a graph theory analysis. These results suggest that unilateral sensory input damage not only alters the activity of the sensory areas but also reshapes the regional and circuit functional organization of the cognitive control network.