Deep brain stimulation has shed new light on the central role of the prefrontal cortex (PFC) in obsessive compulsive disorder (OCD). We explored this structure from a functional perspective, synchronizing neuroimaging and cognitive measures.
Methods and Findings
This case-control cross-sectional study compared 15 OCD patients without comorbidities and not currently on serotonin reuptake inhibitors or cognitive behavioural therapy with 15 healthy controls (matched for age, sex and education level) on resting-state 18FDG-PET scans and a neuropsychological battery assessing executive functions. We looked for correlations between metabolic modifications and impaired neuropsychological scores. Modifications in glucose metabolism were found in frontal regions (orbitofrontal cortex and dorsolateral cortices), the cingulate gyrus, insula and parietal gyrus. Neuropsychological differences between patients and controls, which were subtle, were correlated with the metabolism of the prefrontal, parietal, and temporal cortices.
As expected, we confirmed previous reports of a PFC dysfunction in OCD patients, and established a correlation with cognitive deficits. Other regions outside the prefrontal cortex, including the dorsoparietal cortex and the insula, also appeared to be implicated in the pathophysiology of OCD, providing fresh insights on the complexity of OCD syndromes.
Attentional biases have been proposed to contribute to symptom maintenance in Posttraumatic Stress Disorder (PTSD), although the neural correlates of these processes have not been well defined; this was the goal of the present study. We administered an attention bias task, the dot probe, to a sample of 37 (19 control, 18 PTSD+) traumatized African-American adults during fMRI. Compared to controls, PTSD+ participants demonstrated increased activation in the dorsolateral prefrontal cortex (dlPFC) in response to threat cue trials. In addition, attentional avoidance of threat corresponded with increased ventrolateral prefrontal cortex (vlPFC) and dorsal anterior cingulate cortex (dACC) activation in the PTSD group, a pattern that was not observed in controls. These data provide evidence to suggest that relative increases in dlPFC, dACC and vlPFC activation represent neural markers of attentional bias for threat in individuals with PTSD, reflecting selective disruptions in attentional control and emotion processing networks in this disorder.
Attention bias; PTSD; Threat; fMRI; Prefrontal cortex; Neuroimaging; Posttraumatic Stress Disorder; Anterior cingulate cortex; Dorsolateral prefrontal cortex; Cognition
Functional magnetic resonance imaging was used to investigate the role of the hippocampus, amygdala and medial prefrontal cortex (mPFC) in a contextual conditioning and extinction paradigm provoking anxiety. Twenty-one healthy persons participated in a differential context conditioning procedure with two different background colours as contexts. During acquisition increased activity to the conditioned stimulus (CS+) relative to the CS− was found in the left hippocampus and anterior cingulate cortex (ACC). The amygdala, insula and inferior frontal cortex were differentially active during late acquisition. Extinction was accompanied by enhanced activation to CS+ vs. CS− in the dorsal anterior cingulate cortex (dACC). The results are in accordance with animal studies and provide evidence for the important role of the hippocampus in contextual learning in humans. Connectivity analyses revealed correlated activity between the left posterior hippocampus and dACC (BA32) during early acquisition and the dACC, left posterior hippocampus and right amygdala during extinction. These data are consistent with theoretical models that propose an inhibitory effect of the mPFC on the amygdala. The interaction of the mPFC with the hippocampus may reflect the context-specificity of extinction learning.
anxiety; fear learning; functional connectivity; functional magnetic resonance imaging (fMRI)
Individuals with posttraumatic stress disorder (PTSD) show altered cognition when trauma-related material is present. PTSD may lead to enhanced processing of trauma-related material, or it may cause impaired processing of trauma-unrelated information. However, other forms of emotional information may also alter cognition in PTSD. In this review, we discuss the behavioral and neural effects of emotion processing on cognition in PTSD, with a focus on neuroimaging results. We propose a model of emotion-cognition interaction based on evidence of two network models of altered brain activation in PTSD. The first is a trauma-disrupted network made up of ventrolateral PFC, dorsal anterior cingulate cortex (ACC), hippocampus, insula, and dorsomedial PFC that are differentially modulated by trauma content relative to emotional trauma-unrelated information. The trauma-disrupted network forms a subnetwork of regions within a larger, widely recognized network organized into ventral and dorsal streams for processing emotional and cognitive information that converge in the medial PFC and cingulate cortex. Models of fear learning, while not a cognitive process in the conventional sense, provide important insights into the maintenance of the core symptom clusters of PTSD such as re-experiencing and hypervigilance. Fear processing takes place within the limbic corticostriatal loop composed of threat-alerting and threat-assessing components. Understanding the disruptions in these two networks, and their effect on individuals with PTSD, will lead to an improved knowledge of the etiopathogenesis of PTSD and potential targets for both psychotherapeutic and pharmacotherapeutic interventions.
PTSD; emotion processing; cognitive control; neuroimaging; emotion-cognition interactions
Converging neuroimaging research suggests altered emotion neurocircuitry in individuals with posttraumatic stress disorder (PTSD). Emotion activation studies in these individuals have shown hyperactivation in emotion-related regions, including the amygdala and insula, and hypoactivation in emotion-regulation regions, including the medial prefrontal cortex (mPFC) and anterior cingulate cortex (ACC). However, few studies have examined patterns of connectivity at rest in individuals with PTSD, a potentially powerful method for illuminating brain network structure.
Using the amygdala as a seed region, we measured resting-state brain connectivity using 3 T functional magnetic resonance imaging in returning male veterans with PTSD and combat controls without PTSD.
Fifteen veterans with PTSD and 14 combat controls enrolled in our study. Compared with controls, veterans with PTSD showed greater positive connectivity between the amygdala and insula, reduced positive connectivity between the amygdala and hippocampus, and reduced anticorrelation between the amygdala and dorsal ACC and rostral ACC.
Only male veterans with combat exposure were tested, thus our findings cannot be generalized to women or to individuals with non–combat related PTSD.
These results demonstrate that studies of functional connectivity during resting state can discern aberrant patterns of coupling within emotion circuits and suggest a possible brain basis for emotion-processing and emotion-regulation deficits in individuals with PTSD.
A distributed network of brain regions is linked to drug-related cue responding. However, the relationships between smoking cue-induced phasic activity and possible underlying differences in brain structure, tonic neuronal activity and connectivity between these brain areas are as yet unclear. Twenty-two smokers and 22 controls viewed smoking-related and neutral pictures during a functional arterial spin labeling scanning session. T1, resting functional, and diffusion tensor imaging data were also collected. Six brain areas, dorsal lateral prefrontal cortex (dlPFC), dorsal medial prefrontal cortex (dmPFC), dorsal anterior cingulate cortex/cingulate cortex, rostral anterior cingulate cortex (rACC), occipital cortex, and insula/operculum, showed significant smoking cue-elicited activity in smokers when compared with controls and were subjected to secondary analysis for resting state functional connectivity (rsFC), structural, and tonic neuronal activity. rsFC strength between rACC and dlPFC was positively correlated with the cue-elicited activity in dlPFC. Similarly, rsFC strength between dlPFC and dmPFC was positively correlated with the cue-elicited activity in dmPFC while rsFC strength between dmPFC and insula/operculum was negatively correlated with the cue-elicited activity in both dmPFC and insula/operculum, suggesting these brain circuits may facilitate the response to the salient smoking cues. Further, the gray matter density in dlPFC was decreased in smokers and correlated with cue-elicited activity in the same brain area, suggesting a neurobiological mechanism for the impaired cognitive control associated with drug use. Taken together, these results begin to address the underlying neurobiology of smoking cue salience, and may speak to novel treatment strategies and targets for therapeutic interventions.
Smoking cue; anatomical; ASL; DTI; VBM; resting state functional connectivity
Perceived control attenuates pain and pain-directed anxiety, possibly because it changes the emotional appraisal of pain. We examined whether brain areas associated with voluntary reappraisal of emotional experiences also mediate the analgesic effect of perceived control over pain. Using functional magnetic resonance imaging, we compared self-controlled noxious stimuli with physically identical stimuli that were externally controlled. Self-controlled stimulation was accompanied by less pain and anxiety and higher activation in dorsal anterior cingulate (dACC), right dorsolateral, and bilateral anterolateral prefrontal (alPFC) cortices. Activation in dACC and right alPFC was negatively correlated with pain intensity ratings. For externally controlled pain, activation in right alPFC was inversely correlated with the participants' general belief to have control over their lives. Our results are consistent with a reappraisal view of control and suggest that the analgesic effect of perceived control relies on activation of right alPFC. Failure to activate right alPFC may explain the maladaptive effects of strong general control beliefs during uncontrollable pain.
pain; fMRI; prefrontal cortex; cognitive; emotion; analgesia
Methamphetamine (MA)-dependent individuals prefer smaller immediate over larger delayed rewards in delay discounting (DD) tasks. Human and animal data implicate ventral (amygdala, ventral striatum, ventrolateral prefrontal cortex insula) and dorsal (dorsolateral prefrontal cortex, dorsal anterior cingulate cortex and posterior parietal cortex) systems in DD decisions. The ventral system is hypothesized to respond to the salience and immediacy of rewards while the dorsal system is implicated in the process of comparison and choice.
We used functional Magnetic Resonance Imaging to probe the neural correlates of DD in 19 recently abstinent MA-dependent patients and 17 age- and gender-matched controls.
Hard DD choices were associated with greatest activation in bilateral middle cingulate, posterior parietal cortex (PPC), and the right rostral insula. Control subjects showed more activation than MA patients bilaterally in the precuneus and in the right caudate nucleus, anterior cingulate cortex (ACC), and dorsolateral prefrontal cortex (DLPFC). Magnitude of discounting was correlated with activity in the amygdala, DLPFC, posterior cingulate cortex and PPC.
Our findings were consistent with a model wherein dorsal cognitive systems modulate the neural response of ventral regions. Patients addicted to MA, who strongly prefer smaller immediate over larger delayed rewards, activate the dorsal cognitive control system in order to overcome their preference. Activation of the amygdala during choice of delayed rewards was associated with a greater degree of discounting, suggesting that heavily discounting MA-dependent individuals may be more responsive to the negative salience of delayed rewards than controls.
Methamphetamine; Delay discounting; Brain imaging
Stress and alcohol context cues are each associated with alcohol-related behaviors, yet neural responses underlying these processes remain unclear. The present study investigated the neural correlates of stress and alcohol context cue experiences and examined sex differences in these responses. Using functional magnetic resonance imaging, brain responses were examined while 43 right-handed, socially drinking, healthy individuals (23 females) engaged in brief guided imagery of personalized stress, alcohol-cue and neutral-relaxing scenarios. Stress and alcohol-cue exposure increased activity in the cortico-limbic-striatal circuit (p<.01, corrected), encompassing the medial prefrontal cortex (mPFC), orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), left anterior insula, striatum and visuomotor regions (parietal and occipital lobe, and cerebellum). Activity in the right dorsal striatum increased during stress, while bilateral ventral striatum activity was evident during alcohol-cue exposure. Men displayed greater stress-related activations in the mPFC, rostral ACC, posterior insula, amygdala and hippocampus than women, whereas women showed greater alcohol-cue related activity in the superior and middle frontal gyrus (SFG/MFG) than men. Stress-induced anxiety was positively associated with activity in emotion modulation regions, including the medial OFC, ventromedial PFC, left superior-medial PFC and rostral ACC in men, but in women with activation in the SFG/MFG, regions involved in cognitive processing. Alcohol craving was significantly associated with the striatum (encompassing dorsal and ventral) in men, supporting its involvement in alcohol ‘urge’ in healthy men. These results indicate sex differences in neural processing of stress and alcohol-cue experiences, and have implications for sex-specific vulnerabilities to stress- and alcohol-related psychiatric disorders.
Sex differences; Stress; Alcohol cue; Reward; Brain fMRI; Prefrontal Cortex
This study examined the functional specificity of dorsal anterior cingulate cortex (dACC) and medial prefrontal cortex (mPFC) regarding two elements of decision-making: the number of available decision options and the level of expected reward. Eighteen healthy participants were trained to recognize the reward value associated with several visual stimuli, and then were presented with groups of two, three, or four of these stimuli and asked to select the object associated with the highest reward. BOLD activation in dorsomedial prefrontal cortex (dmFC)/dACC was strongly positively associated with increases in the number of decision options but only weakly associated with increases in the level of expected reward. Activation in rostral anterior cingulate cortex (rACC)/mPFC and amygdala was related to increases in the level of expected reward but not increases in the number of decision options. The current results suggest functional specificity with respect to the roles of dACC/dmFC and rACC/mPFC in decision-making.
decision; FMRI; anterior cingulate; caudate; medial prefrontal cortex; amygdala
Fear acquisition and extinction are crucial mechanisms in the etiology and maintenance of anxiety disorders. Moreover, they might play a pivotal role in conveying the influence of genetic and environmental factors on the development of a (more or less) stronger proneness for, or resilience against psychopathology. There are only few insights in the neurobiology of genetically and environmentally based individual differences in fear learning and extinction. In this functional magnetic resonance imaging study, 74 healthy subjects were investigated. These were invited according to 5-HTTLPR/rs25531 (S+ vs. LALA; triallelic classification) and TPH2 (G(-703)T) (T+ vs. T-) genotype. The aim was to investigate the influence of genetic factors and traumatic life events on skin conductance responses (SCRs) and neural responses (amygdala, insula, dorsal anterior cingulate cortex (dACC) and ventromedial prefrontal cortex (vmPFC)) during acquisition and extinction learning in a differential fear conditioning paradigm. Fear acquisition was characterized by stronger late conditioned and unconditioned responses in the right insula in 5-HTTLPR S-allele carriers. During extinction traumatic life events were associated with reduced amygdala activation in S-allele carriers vs. non-carriers. Beyond that, T-allele carriers of the TPH2 (G(−703)T) polymorphism with a higher number of traumatic life events showed enhanced responsiveness in the amygdala during acquisition and in the vmPFC during extinction learning compared with non-carriers. Finally, a combined effect of the two polymorphisms with higher responses in S- and T-allele carriers was found in the dACC during extinction. The results indicate an increased expression of conditioned, but also unconditioned fear responses in the insula in 5-HTTLPR S-allele carriers. A combined effect of the two polymorphisms on dACC activation during extinction might be associated with prolonged fear expression. Gene-by-environment interactions in amygdala and vmPFC activation may reflect a neural endophenotype translating genetic and adverse environmental influences into vulnerability for or resilience against developing affective psychopathology.
Previous neuroimaging studies have implicated the prefrontal cortex (PFC) and nearby brain regions in deception. This is consistent with the hypothesis that lying involves the executive control system. To date, the nature of the contribution of different aspects of executive control to deception, however, remains unclear. In the present study, we utilized an activation likelihood estimate (ALE) method of meta-analysis to quantitatively identify brain regions that are consistently more active for deceptive responses relative to truthful responses across past studies. We then contrasted the results with additional ALE maps generated for 3 different aspects of executive control: working memory, inhibitory control, and task switching. Deception-related regions in dorsolateral PFC and posterior parietal cortex were selectively associated with working memory. Additional deception regions in ventrolateral PFC, anterior insula, and anterior cingulate cortex were associated with multiple aspects of executive control. In contrast, deception-related regions in bilateral inferior parietal lobule were not associated with any of the 3 executive control constructs. Our findings support the notion that executive control processes, particularly working memory, and their associated neural substrates play an integral role in deception. This work provides a foundation for future research on the neurocognitive basis of deception.
anterior cingulate; fMRI; lie detection; lying; neuroimaging; prefrontal cortex
Convergent data from neuroimaging, neuropsychological, genetic and neurochemical studies in attention-deficit/hyperactivity disorder (ADHD) have implicated dysfunction of the dorsolateral prefrontal cortex (DLPFC) and dorsal anterior cingulate cortex (dACC), which form the cortical arm of the frontostriatal network supporting executive functions. Furthermore, besides the DLPFC and dACC, structural and functional imaging studies have shown abnormalities in key brain regions within distributed cortical networks supporting attention. The conceptualization of neural systems biology in ADHD aims at the understanding of what organizing principles have been altered during development within the brain of a person with ADHD. Characterizing these neural systems using neuroimaging could be critical for the description of structural endophenotypes, and may provide the capability of in vivo categorization and correlation with behavior and genes.
Attention-deficit/hyperactivity disorder; Magnetic resonance imaging; Diffusion tensor imaging; Neural systems; Executive function; Attention; Impulsivity; Neuroanatomy
The study examined the relationship between risk-taking behavior during selection of monetary rewards and activations in the anterior cingulate cortex (ACC), orbitofrontal cortex (OFC) and medial prefrontal cortex (mPFC), brain regions that are associated with decision-making. Thirty-three adolescents with no personal or family history of any psychiatric illness were administered the Wheel of Fortune (WOF) task using a functional magnetic resonance imaging protocol. The WOF is a computerized two-choice, probabilistic monetary reward task. Selection of a reward, particularly a low-probability/high-magnitude reward choice, induced greater activations in dorsal ACC, ventrolateral OFC and mPFC than the control condition. Although similar findings have been reported by earlier studies, the results from this study were not impacted by reaction times and expected values and persisted even after controlling for sociodemographic factors. Post-hoc analysis revealed greater activation of ACC and mPFC in response to selection of rewards of larger magnitude than those of smaller magnitude when the probability of reward was maintained constant. Adolescents with greater frequency of high-risk behavior (defined as low-probability/high magnitude reward choice) had lower activation of ACC, OFC and mPFC than those who engaged in this behavior less frequently. These findings suggest individual differences in prefrontal cortical function with regards to decision-making process in adolescents.
Neurobiology; choice; selection; adolescents; decision-making; rewards
The amygdala's contribution to emotion, cognition and behavior depends on its interactions with subcortical and cortical regions. Amygdala lesions result in altered functional activity in connected regions, but it is not known whether there might be long-term structural sequelae as well. We hypothesized that developmental bilateral amygdala lesions would be associated with specific gray matter morphometric abnormalities in the ventromedial prefrontal cortex (vmPFC), anterior cingulate cortex (ACC) and the ventral visual stream. We conducted regions of interest and vertex-based analyses of structural MRI data acquired in two patients with long-standing focal bilateral amygdala lesions (S.M. and A.P.), compared to gender- and age-matched healthy comparison subjects. Both patients showed significant proportional increases in gray matter volume of the vmPFC. Cortical thickness was increased in the vmPFC and ACC and decreased in the ventral visual stream. There were no morphometric changes in dorsolateral prefrontal cortex or dorsal visual stream cortices. These findings support the hypothesis that cortical regions strongly connected with the amygdala undergo morphometric changes with long-standing amygdala damage. This is the first evidence in humans of the remote alteration of brain morphology in association with amygdala lesions, and will help in interpreting the structural and functional consequences of amygdala pathology in neuropsychiatric disorders.
amygdala; lesions; morphometry; plasticity; prefrontal cortex; ventromedial
Altered cognitive control is implicated in the shaping of cocaine dependence. One of the key component processes of cognitive control is error monitoring. Our previous imaging work highlighted greater activity in distinct cortical and subcortical regions including the dorsal anterior cingulate cortex (dACC), thalamus and insula when participants committed an error during the stop signal task (Li et al., 2008b). Importantly, dACC, thalamic and insular activity has been associated with drug craving. One hypothesis is that the intense interoceptive activity during craving prevents these cerebral structures from adequately registering error and/or monitoring performance. Alternatively, the dACC, thalamus and insula show abnormally heightened responses to performance errors, suggesting that excessive responses to salient stimuli such as drug cues could precipitate craving. The two hypotheses would each predict decreased and increased activity during stop error (SE) as compared to stop success (SS) trials in the SST. Here we showed that cocaine dependent patients (PCD) experienced greater subjective feeling of loss of control and cocaine craving during early (average of day 6) compared to late (average of day 18) abstinence. Furthermore, compared to PCD during late abstinence, PCD scanned during early abstinence showed increased thalamic as well as insular but not dACC responses to errors (SE>SS). These findings support the hypothesis that heightened thalamic reactivity to salient stimuli co-occur with cocaine craving and loss of self control.
thalamus; subcortical; imaging; neuropsychology; fMRI; self control; craving; cocaine abuse
Vulnerability to drug abuse is related to both reward seeking and impulsivity, two constructs thought to have a biological basis in the prefrontal cortex (PFC). This review addresses similarities and differences in neuroanatomy, neurochemistry and behavior associated with PFC function in rodents and primates. Emphasis is placed on monoamine and amino acid neurotransmitter systems located in anatomically distinct subregions: medial prefrontal cortex (mPFC); lateral prefrontal cortex (lPFC); anterior cingulate cortex (ACC); and orbitofrontal cortex (OFC). While there are complex interconnections and overlapping functions among these regions, each is thought to be involved in various functions related to health-related risk behaviors and drug abuse vulnerability. Among the various functions implicated, evidence suggests that mPFC is involved in reward processing, attention and drug reinstatement; lPFC is involved in decision-making, behavioral inhibition and attentional gating; ACC is involved in attention, emotional processing and self-monitoring; and OFC is involved in behavioral inhibition, signaling of expected outcomes and reward/punishment sensitivity. Individual differences factors (e.g., age and sex) influence functioning of these regions, which, in turn, impacts drug abuse vulnerability. Implications for the development of drug abuse prevention and treatment strategies aimed at engaging PFC inhibitory processes that may reduce risk-related behaviors are discussed, including the design of effective public service announcements, cognitive exercises, physical activity, direct current stimulation, feedback control training and pharmacotherapies. A major challenge in drug abuse prevention and treatment rests with improving intervention strategies aimed at strengthening PFC inhibitory systems among at-risk individuals.
Anterior cingulate cortex; Dopamine; Drug abuse; GABA; Glutamate; Impulsivity; Lateral prefrontal cortex; Medial prefrontal cortex; Norepinephrine; Orbitofrontal cortex; Serotonin
The neuroanatomical correlates of depression remain unclear. Functional imaging data have associated depression with abnormal patterns of activity in prefrontal cortex (PFC), including the ventromedial (vmPFC) and dorsolateral (dlPFC) sectors. If vmPFC and dlPFC are critical neural substrates for the pathogenesis of depression, then damage to either area should affect the expression of depressive symptoms. Using patients with brain lesions we show that, relative to nonfrontal lesions, bilateral vmPFC lesions are associated with markedly low levels of depression, whereas bilateral dorsal PFC lesions (involving dorsomedial and dorsolateral areas in both hemispheres) are associated with substantially higher levels of depression. These findings demonstrate that vmPFC and dorsal PFC are critically and causally involved in depression, although with very different roles: vmPFC damage confers resistance to depression, whereas dorsal PFC damage confers vulnerability.
depression; emotion; prefrontal cortex; ventromedial; dorsolateral; neuropathology
Psychological conditions affect pain responses in the human anterior cingulate cortex (ACC) according to brain imaging analysis. The rodent prefrontal cortex (PFC) including cingulate areas is also related to the affective dimension of pain. We previously reported PFC nociceptive responses inhibited by inputs from the amygdala, such as with dopamine (DA) D2 receptor (D2R) blockers, to show decreased effect on amygdala projections. In this study, we examined whether direct projections from the ventral tegmental area (VTA) to the PFC affect nociceptive responses in the PFC.
High frequency stimulation (HFS, 50 Hz, 30 s) delivered to the VTA produced long-lasting suppression (LLS) of nociceptive responses in the rat PFC including cingulate and prelimbic areas. Nociceptive responses evoked by mechanical pressure stimulation (2 s duration at 500 g constant force) applied to the tails of urethane-anesthetized rats were recorded using extracellular unit recording methods in the PFC. HFS delivered to the VTA, which has been reported to increase DA concentrations in the PFC, significantly suppressed nociceptive responses. The LLS of nociceptive responses persisted for about 30 minutes and recovered to the control level within 60 min after HFS. We also demonstrated local microinjection of a selective D2 agonist of DA receptors to induce LLS of mechanical nociceptive responses, while a D2 but not a D1 antagonist impaired the LLS evoked by HFS. In contrast, DA depletion by a 6-hydroxydopamine injection or a low concentration of DA induced by a κ-opiate receptor agonist injected into the VTA had minimal effect on nociceptive responses in the PFC.
HFS delivered to VTA inhibited nociceptive responses for a long period in PFC. DA D2R activation mediated by local D2 agonist injection also induced LLS of mechanical nociceptive responses. The mesocortical DA system may modify PFC nociceptive responses via D2 activity.
ACC; PFC; Dopamine; D2R; Pain; Parkinson disease; VTA
The current paper examines the functional contributions of the amygdala and ventromedial prefrontal cortex (vmPFC) and the evidence that the functioning of these systems is compromised in individuals with psychopathy. The amygdala is critical for the formation of stimulus–reinforcement associations, both punishment and reward based, and the processing of emotional expressions. vmPFC is critical for the representation of reinforcement expectancies and, owing to this, decision making. Neuropsychological and neuroimaging data from individuals with psychopathy are examined. It is concluded that these critical functions of the amygdala and vmPFC, and their interaction, are compromised in individuals with the disorder. It is argued that these impairments lead to the development of psychopathy.
amygdala; venromedial perfrontal cortex; psychopathy
A neurocognitive endophenotype has been proposed for stimulant dependence, based on behavioral measures of inhibitory response control associated with white matter changes in the frontal cortex. This study investigated the functional neuroimaging correlates of inhibitory response control, as functional activity serves as a more dynamic measure than brain structure, allowing refinement of the suggested endophenotype. Stimulant-dependent individuals (SDIs), their unaffected siblings (SIBs), and healthy controls (CTs) performed the stop-signal task, including stop-signal reaction time (SSRT) as a measure of response inhibition, while undergoing functional magnetic resonance imaging. SDIs had impaired response inhibition accompanied by hypoactivation in the ventrolateral prefrontal cortex (PFC). In addition, they demonstrated hypoactivation in the anterior cingulate when failing to stop. In contrast, no hypoactivations were noted in their unaffected SIBs. Rather, they exhibited increased activation in the dorsomedial PFC relative to controls, together with inhibitory performance that was intermediate between that of the stimulant group and the healthy CT group. Such hyperactivations within the neurocircuitry underlying response inhibition and control are suggestive of compensatory mechanisms that could be protective in nature or could reflect coping with a pre-existing vulnerability, thus expressing potential aspects of resilience. The functional activation associated with response inhibition and error monitoring showed differential patterns of results between SDIs and their unaffected first-degree relatives, suggesting that the proposed endophenotype does not generalize to functional brain activity.
addiction & substance abuse; biological psychiatry; imaging; clinical or preclinical; psychiatry & behavioral sciences; endophenotypes; fMRI; stimulant dependence; stop-signal; cognitive control; drug use
To better understand the reward circuitry in human brain, we conducted activation likelihood estimation (ALE) and parametric voxel-based meta-analyses (PVM) on 142 neuroimaging studies that examined brain activation in reward-related tasks in healthy adults. We observed several core brain areas that participated in reward-related decision making, including the nucleus accumbens (NAcc), caudate, putamen, thalamus, orbitofrontal cortex (OFC), bilateral anterior insula, anterior (ACC) and posterior (PCC) cingulate cortex, as well as cognitive control regions in the inferior parietal lobule and prefrontal cortex (PFC). The NAcc was commonly activated by both positive and negative rewards across various stages of reward processing (e.g., anticipation, outcome, and evaluation). In addition, the medial OFC and PCC preferentially responded to positive rewards, whereas the ACC, bilateral anterior insula, and lateral PFC selectively responded to negative rewards. Reward anticipation activated the ACC, bilateral anterior insula, and brain stem, whereas reward outcome more significantly activated the NAcc, medial OFC, and amygdala. Neurobiological theories of reward-related decision making should therefore distributed and interrelated representations of reward valuation and valence assessment into account.
meta-analysis; reward; nucleus accumbens; orbitofrontal cortex; anterior cingulate cortex; anterior insula
The anterior cingulate cortex (ACC) has been implicated in both preparatory attention (i.e., selecting behaviorally relevant stimuli) and in detecting errors. We recorded from the rat ACC and medial prefrontal cortex (mPFC), which is functionally homologous with the primate dorsolateral PFC, during an attention task. The 3-choice serial reaction time task requires a rat to orient toward and divide attention between 3 brief (300 msec duration) light stimuli presented in random order across nose poke holes in an operant chamber. In both the ACC and mPFC, we found that neural activity was related to the level of preparatory (pre-cue) attention and subsequent correct or incorrect choice, in that the magnitude of the single units' response to the cue was lower on incorrect trials and was not different from baseline on unattended trials. This preparatory neural activity consisted of both excitatory and inhibitory phasic responses. The number of units responding to the cue was similarly graded, in that fewer units exhibited phasic responses to the cue on incorrect and unattended trials, compared to correct trials. Although preparatory activity was found in both the ACC and mPFC, activity after incorrect nose pokes, which may be related to error detection, were only observed in the ACC. Thus, during the same behavioral sequence, the ACC encodes both error-related events and preparatory attention, whereas the mPFC only participates in preparatory attention. The finding of substantial inhibitory activity during the preparatory period suggests a critical role for inhibition of pyramidal cells in PFC-mediated cognitive functions.
attention-deficit hyperactivity disorder; dopamine; prefrontal cortex; schizophrenia; single unit; rat
The anterior medial prefrontal cortex (aMPFC) is consistently active during personally salient decisions, yet the differential contributory processes of this region along the dorsal—ventral axis are less understood. Using a self-appraisal decision-making task and functional magnetic resonance imaging, we demonstrated task-dependent connectivity of ventral aMPFC with amygdala, insula, and nucleus accumbens, and dorsal aMPFC connectivity with dorsolateral PFC and bilateral hippocampus. These aMPFC networks appear to subserve distinct contributory processes inherent to self-appraisal decisions, specifically a dorsally mediated cognitive and a ventrally mediated affective/self-relevance network.
It has been proposed that self-awareness (SA), a multifaceted phenomenon central to human consciousness, depends critically on specific brain regions, namely the insular cortex, the anterior cingulate cortex (ACC), and the medial prefrontal cortex (mPFC). Such a proposal predicts that damage to these regions should disrupt or even abolish SA. We tested this prediction in a rare neurological patient with extensive bilateral brain damage encompassing the insula, ACC, mPFC, and the medial temporal lobes. In spite of severe amnesia, which partially affected his “autobiographical self”, the patient's SA remained fundamentally intact. His Core SA, including basic self-recognition and sense of self-agency, was preserved. His Extended SA and Introspective SA were also largely intact, as he has a stable self-concept and intact higher-order metacognitive abilities. The results suggest that the insular cortex, ACC and mPFC are not required for most aspects of SA. Our findings are compatible with the hypothesis that SA is likely to emerge from more distributed interactions among brain networks including those in the brainstem, thalamus, and posteromedial cortices.