We used event-related potentials to investigate how aging affects local contextual processing. Local context was defined as the occurrence of a short predictive series of visual stimuli before delivery of a target event. Stimuli were presented to either the left or right visual field and consisted of 15% targets (downward facing triangle) and 85% of equal numbers of three types of standards (triangles facing left, upwards and right). Recording blocks consisted of targets preceded by either randomized sequences of standards or by sequences including a three-standard predictive sequence signaling the occurrence of a subsequent target event. Subjects pressed a button in response to targets. Predictive local context affected target detection by reducing the duration of stimulus evaluation compared to detection of non-predictive random targets comparably for both young and older adults, as shown by a P3b latency shift. The peak of an earlier latency context positivity, which was seen only in the predicted compared to the random target condition, was prolonged in the older population compared to young adults. Finally, older subjects elicited a late sustained positivity in the predictive condition, not seen in the younger subjects. Taken together, theses findings suggest that local contextual effects on target detection processes are altered with age.
aging; context; P3b; EEG; context positivity
We investigated the effects of implicit local contextual processing using behavioral and electrophysiological measures. EEG recording blocks consisted of targets preceded by either randomized sequences of standards or by sequences including a predictive sequence signaling the occurrence of a target event. Subjects performed two sessions: in the first the regularity of the predictive sequence was implicit, while in the second this regularity was made explicit. Subjects pressed a button in response to targets. Both the implicit and explicit sessions showed shorter reaction times and peak P3b latencies for predicted versus random targets, although to a greater extent in the explicit session. In both sessions the middle and last most-informative stimuli of the three-standard predictive sequence induced a significant larger P3b compared with randomized standards. The findings show that local contextual information is processed implicitly, but that this modulation was significantly greater when subjects were explicitly instructed to attend to target-predictive contextual information. The findings suggest that top-down attentional networks have a role in modulating the extent to which contextual information is utilized.
Functional clusters of neurons in the monkey prefrontal and anterior cingulate cortex are involved in guiding attention to the most valuable objects in a scene.
Attentional control ensures that neuronal processes prioritize the most relevant stimulus in a given environment. Controlling which stimulus is attended thus originates from neurons encoding the relevance of stimuli, i.e. their expected value, in hand with neurons encoding contextual information about stimulus locations, features, and rules that guide the conditional allocation of attention. Here, we examined how these distinct processes are encoded and integrated in macaque prefrontal cortex (PFC) by mapping their functional topographies at the time of attentional stimulus selection. We find confined clusters of neurons in ventromedial PFC (vmPFC) that predominantly convey stimulus valuation information during attention shifts. These valuation signals were topographically largely separated from neurons predicting the stimulus location to which attention covertly shifted, and which were evident across the complete medial-to-lateral extent of the PFC, encompassing anterior cingulate cortex (ACC), and lateral PFC (LPFC). LPFC responses showed particularly early-onset selectivity and primarily facilitated attention shifts to contralateral targets. Spatial selectivity within ACC was delayed and heterogeneous, with similar proportions of facilitated and suppressed responses during contralateral attention shifts. The integration of spatial and valuation signals about attentional target stimuli was observed in a confined cluster of neurons at the intersection of vmPFC, ACC, and LPFC. These results suggest that valuation processes reflecting stimulus-specific outcome predictions are recruited during covert attentional control. Value predictions and the spatial identification of attentional targets were conveyed by largely separate neuronal populations, but were integrated locally at the intersection of three major prefrontal areas, which may constitute a functional hub within the larger attentional control network.
To navigate within an environment filled with sensory stimuli, the brain must selectively process only the most relevant sensory information. Identifying and shifting attention to the most relevant sensory stimulus requires integrating information about its sensory features as well as its relative value, that is, whether it's worth noticing. In this study, we describe groups of neurons in the monkey prefrontal cortex that convey signals relating to the value of a stimulus and its defining feature and location at the very moment when attention is shifted to the stimulus. We found that signals conveying information about value were clustered in a ventromedial prefrontal region, and were separated from sensory signals within the anterior cingulate cortex and the lateral prefrontal cortex. The integration of valuation and other “top-down” processes, however, was achieved by neurons clustered at the intersection of ventromedial, anterior cingulate, and lateral prefrontal cortex. We conclude that valuation processes are recruited when attention is shifted, independent of any overt behavior. Moreover, our analysis suggests that valuation processes can bias the initiation of attention shifts, as well as ensure sustained attentional focusing.
The prefrontal cortex (PFC) has been described as important for maintaining and implementing contextual information in the service of goal-oriented behavior. Accordingly, impairments in context processing are thought to underlie cognitive deficits associated with schizophrenia, a clinical disorder that has been linked to PFC dysfunction (Servan-Schreiber, Cohen & Steingard, 1996). However, task switching, a cognitive ability linked to PFC function, has not been consistently impaired in schizophrenia. In this experiment, we assessed whether task-switching performance would be selectively impaired for patients when context demands were high. In the rule switching condition, a switch required the updating of the relevant task response rules whereas perceptual switching did not entail a switching of contextual information. Instead, a perceptual switch entailed a shift of visuospatial attention to the relevant feature. A second goal was to determine whether potential deficits in context switching would be observed in schizophrenia even in situations when these patients do not need to overcome a prepotent response. Studies of context processing have typically required patients with schizophrenia to use contextual rules to overcome prepotent response tendencies whereas our switching paradigm did not require the inhibition of a competing response. Patients were much slower to switch tasks than controls when contextual rules switched from one trial to the next whereas their performance was intact when the switch occurred between different feature sets and contextual demands were low. Our results demonstrate that context-processing deficits are observable in schizophrenia even when there is no prepotent response tendency to inhibit. Moreover, our results suggest that PFC impairments influence performance primarily when patients are required to switch the application of one explicit rule to another.
cognitive control; task switching; prefrontal cortex
Rostral prefrontal cortex (PFC) is known to be involved in source memory, the ability to recollect contextual information about an event. However it is unclear whether subregions of rostral PFC may be differentially engaged during the recollection of different kinds of source detail. We used event related functional MRI to contrast two forms of source recollection: (1) recollection of whether stimuli had previously been perceived or imagined, and (2) recollection of which of two temporally distinct lists those stimuli had been presented in. Lateral regions of rostral PFC were activated in both tasks. However medial regions of rostral PFC were activated only when participants were required to recollect source information for self-generated, “imagined” stimuli, indicating a specific role in self-referential processing. In addition, reduced activity in a region of medial ventro-caudal PFC/basal forebrain was associated with making “imagined-to-perceived” confabulation errors. These results suggest that whilst the processing resources supported by some regions of lateral rostral PFC play a general role in source recollection, those supported by medial rostral PFC structures may be more specialised in their contributions.
Functional magnetic resonance imaging (fMRI); Cognitive control; Source memory; Reality monitoring; Self-referential processing; Confabulation
Neuroimaging studies have reported increased prefrontal cortex (PFC) activity during temporal context retrieval versus recognition memory. However, it remains unclear if these activations reflect PFC contributions to domain-general executive control processes or domain-specific retrieval processes. To gain a better understanding of the functional roles of these various PFC regions during temporal context retrieval we propose it is necessary to examine PFC activity across tasks from different domains, in which parallel manipulations are included targeting specific cognitive processes. In the current fMRI study, we examined domain-general and domain-specific PFC contributions to temporal context retrieval by increasing stimulus (but maintaining response number) and increasing response number (but maintaining stimulus number) across temporal context memory and ordering control tasks, for faces. The control task required subjects to order faces from youngest to oldest. Our behavioral results indicate that the combination of increased stimulus and response numbers significantly increased task difficulty for temporal context retrieval and ordering tasks. Across domains, increasing stimulus number, while maintaining response numbers, caused greater right lateral premotor cortex (BA 6/8) activity; whereas increasing response number, while maintaining stimulus number, caused greater domain-general left DLPFC (BA 9) and VLPFC (BA 44/45) activity. In addition, we found domain-specific right DLPFC (BA 9) activity only during retrieval events. These results highlight the functional heterogeneity of frontal cortex, and suggest its involvement in temporal context retrieval is related to its role in various cognitive control processes.
episodic memory; working memory; selection; monitoring; face stimuli; fMRI
Environmental cues that once predicted reward can restore extinguished behavior directed toward that reward. This process may be modeled by the Pavlovian-instrumental transfer (PIT) paradigm where a previously learned Pavlovian conditioned stimulus (CS) elicits a representation of the reward associated with that CS, prompts motivation towards the absent reward, and triggers an instrumental action. We recorded in the medial and orbital prefrontal cortex (mPFC and OFC) and dorsal striatum of freely moving rats during PIT and found that a Pavlovian CS, as compared to neutral or no stimuli, amplified the phasic neuronal responses to instrumental nosepokes ("transfer" event). In mPFC and OFC, but not the dorsal striatum, representation of the transfer event correlated with the strength of PIT behavior. Neurons in all three regions showed CS-selective amplification of Pavlovian approaches toward the reward delivery site. Whereas striatal neurons represented transfer and approach behavior through mostly segregated neuronal subsets, overlapping subsets represented these events in the mPFC and OFC. These findings suggest that parallel phasic activation of mPFC and OFC neuronal subsets participates in the transfer from Pavlovian incentives to instrumental actions.
Pavlovian Conditioning; Instrumental Conditioning; Cue-triggered Motivation; Orbitofrontal cortex; Freely Moving Rat
The detection of stimuli is critical for an animal’s survival . However, it is not adaptive for an animal to respond automatically to every stimulus that is present in the environment [2–5]. Since the prefrontal cortex (PFC) plays a key role in executive function [6–8], we hypothesized that PFC activity should be involved in context-dependent responses to uncommon stimuli. To test this hypothesis, monkeys participated in a same-different task, a variant of an oddball task . During this task, a monkey heard multiple presentations of a “reference” stimulus that was followed by a “test” stimulus and reported whether these stimuli were the same or different. While they participated in this task, we recorded from neurons in the ventrolateral prefrontal cortex (vPFC; a cortical area involved in aspects of non-spatial auditory processing [9, 10]). We found that vPFC activity was correlated with the monkeys’ choices. This finding demonstrates a direct link between single neurons and behavioral choices in the PFC on a non-spatial auditory task.
Across species, serotonin (5-HT) depletion in the prefrontal cortex (PFC) has been shown to cause impaired performance on tests of cognitive flexibility and the processing of affective information (e.g. information with an ‘emotional’ content). While recent work has explored the specific role of the orbital PFC herein, the role of the medial PFC remains unclear.
The aim of our current experiments was to study the role of medial PFC 5-HT in both the processing of affective information and reversal learning across stimulus modalities.
Materials and methods
To this end, we selectively destroyed 5-HT terminals in the medial PFC of male Wistar rats by means of local infusion of the toxin 5,7-dihydroxytryptamine. Both control and lesioned animals were tested in two reversal learning paradigms with either spatial or odour cues and an affective switch from non-preferred to preferred food rewards.
Our results indicate that a pellet switch during reversal learning impaired performance in control animals but not in lesioned animals, independent of the stimulus modality.
These results indicate that lesioned animals are not guided in their behaviour by the affective value of the reward like intact animals and thus that medial prefrontal 5-HT is needed for affective processing in goal-directed behaviour.
Cognitive flexibility; Medial prefrontal cortex; 5,7-DHT; Reversal learning; Affective processing
The ventromedial prefrontal cortex (vmPFC) is thought to be related to emotional experience and to the processing of stimulus and action values. However, little is known about how single vmPFC neurons process the prediction and reception of rewards and punishments. We recorded from monkey vmPFC neurons in an experimental situation with alternating blocks, one in which rewards were delivered and one in which punishments were delivered. Many vmPFC neurons changed their activity between blocks. Importantly, neurons in ventral vmPFC were persistently more active in the appetitive “reward” block, whereas neurons in dorsal vmPFC were persistently more active in the aversive “punishment” block. Furthermore, within ventral vmPFC, posterior neurons phasically encoded probability of reward, whereas anterior neurons tonically encoded possibility of reward. We found multiple distinct nonlinear valuation mechanisms within the primate prefrontal cortex. Our findings suggest that different subregions of vmPFC contribute differentially to the processing of valence. By conveying such multidimensional and nonlinear signals, the vmPFC may enable flexible control of decisions and emotions to adapt to complex environments.
Hippocampus and prefrontal cortex (PFC) process spatiotemporally discrete events while maintaining goal-directed task demands. Although some studies have reported that neural activities in the two regions are coordinated, such observations have rarely been reported in an object-place paired-associate (OPPA) task in which animals must learn an object-in-place rule. In this study, we recorded single units and local field potentials simultaneously from the CA1 subfield of the hippocampus and PFC as rats learned that object A, but not object B, was rewarded in place 1, but not in place 2 (vice versa for object B). Both hippocampus and PFC are required for normal performance in this task. PFC neurons fired in association with the regularity of the occurrence of a certain type of event independent of space, whereas neuronal firing in CA1 was spatially localized for representing a discrete place. Importantly, the differential firing patterns were observed in tandem with common learning-related changes in both regions. Specifically, once OPPA learning occurred and rats used an object-in-place strategy, (i) both CA1 and PFC neurons exhibited spatially more similar and temporally more synchronized firing patterns, (ii) spiking activities in both regions were more phase-locked to theta rhythms, (iii) CA1-mPFC coherence in theta oscillation was maximal before entering a critical place for decision making. The results demonstrate differential as well as common neural dynamics between hippocampus and PFC in acquiring the OPPA task and strongly suggest that both regions form a unified functional network for processing an episodic event.
We employed an EEG paradigm manipulating predictive context to dissociate the neural dynamics of anticipatory mechanisms. Subjects either detected random targets or targets preceded by a predictive sequence of three distinct stimuli. The last stimulus in the 3-stimulus sequence (decisive stimulus) did not require any motor response but 100% predicted a subsequent target event. We show that predictive context optimizes target processing via the deployment of distinct anticipatory mechanisms at different times of the predictive sequence. Prior to the occurrence of the decisive stimulus, enhanced attentional preparation was manifested by reductions in the alpha oscillatory activities over visual cortices, resulting in facilitation of processing of the decisive stimulus. Conversely, the subsequent 100% predictable target event did not reveal deployment of attentional preparation in the visual cortices, but elicited enhanced motor preparation mechanisms, indexed by an increased contingent negative variation (CNV) and reduced mu oscillatory activities over motor cortices before movement onset. The present results provide evidence that anticipation operates via different attentional and motor preparation mechanisms by selectively pre-activating task-dependent brain areas as predictability gradually increases.
attention; motor preparation; alpha; mu; beta
The ability to recognize the behavioral significance, or category membership, of sensory stimuli is critical for interpreting the meaning of events in our environment. Prior neurophysiological studies of visual categorization found categorical representations of stimuli in prefrontal cortex (PFC), an area closely associated with cognitive and executive functions. Recent studies have also identified neuronal category signals in parietal areas typically associated with visual-spatial processing. It has been proposed that category-related signals in parietal cortex and other visual areas may result from “top-down” feedback from PFC. We directly compared neuronal activity in the lateral intraparietal (LIP) area and PFC in monkeys performing a visual motion categorization task. Here we show that LIP shows stronger, more reliable, and shorter latency category signals than PFC. This suggests that LIP is strongly involved in visual categorization, and argues against the idea that parietal category signals arise from feedback from PFC during this task.
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
We used the P300 component to investigate how changes in local context influenced the ability to detect target stimuli. Local context was defined as the occurrence of a short predictive series of stimuli before delivery of a target event. EEG was recorded in 12 subjects during auditory and visual sessions. Stimuli were presented in the center of the auditory and visual field and consisted of 15% targets (1000 Hz tone or downward facing triangle) and 85% of equal amounts of three types of standards (1500 Hz, 2000 Hz and 2500 Hz tones or triangles facing left, upwards and right). Recording blocks consisted of targets preceded by either randomized sequences of standards or by sequences including a three-standard predictive sequence signaling the occurrence of a subsequent target event. Subjects pressed a button in response to targets. Peak target P300 (P3b) amplitude and latency were evaluated for targets after predictive and non-predictive sequences using conventional averaging and a novel single-trial analysis procedure. Reaction times were shorter for predictable targets than for non-predicted targets. P3b latency was shorter for predicted targets than for non-predictive targets, and there were no significant P3b amplitude differences between predicted and random targets, as determined by both conventional averaging and single-trial analysis. Comparable effects on amplitude and latency were observed in both the auditory and visual modalities. The results indicate that local context has differential effects on P3b amplitude and latency, and exerts modality independent effects on cognitive processing.
context; P3b; multi-modal; EEG; ASEO
The present experiment tested three hypotheses regarding the function and organization of lateral prefrontal cortex (PFC). The first account (the information cascade hypothesis) suggests that the anterior-posterior organization of lateral PFC is based on the timing with which cue stimuli reduce uncertainty in the action selection process. The second account (the levels-of-abstraction hypothesis) suggests that the anterior-posterior organization of lateral PFC is based on the degree of abstraction of the task goals. The current study began by investigating these two hypotheses, and identified several areas of lateral PFC that were predicted to be active by both the information cascade and levels-of-abstraction accounts. However, the pattern of activation across experimental conditions was inconsistent with both theoretical accounts. Specifically, an anterior area of mid-dorsolateral PFC exhibited sensitivity to experimental conditions that, according to both accounts, should have selectively engaged only posterior areas of PFC. We therefore investigated a third possible account (the adaptive context maintenance hypothesis) that postulates that both posterior and anterior regions of PFC are reliably engaged in task conditions requiring active maintenance of contextual information, with the temporal dynamics of activity in these regions flexibly tracking the duration of maintenance demands. Activity patterns in lateral PFC were consistent with this third hypothesis: regions across lateral PFC exhibited transient activation when contextual information had to be updated and maintained in a trial-by-trial manner, but sustained activation when contextual information had to be maintained over a series of trials. These findings prompt a reconceptualization of current views regarding the anterior-posterior organization of lateral PFC, but do support other findings regarding the active maintenance role of lateral PFC in sequential working memory paradigms.
Adaptive behavior depends on an animal’s ability to ignore uninformative stimuli, such as repeated presentations of the same stimulus, and, instead, detect informative, novel stimuli in its environment. The primate prefrontal cortex (PFC) is known to play a central role in this ability. However, the neural mechanisms underlying the ability to differentiate between repeated and novel stimuli are not clear. We hypothesized that the coupling between different frequency bands of the local field potential (LFP) underlies the PFC’s role in differentiating between repeated and novel stimuli. Specifically, we hypothesized that whereas the presentation of a novel-stimulus induces strong cross-frequency coupling, repeated presentations of the same stimulus attenuates this coupling. To test this hypothesis, we recorded LFPs from the ventrolateral PFC (vPFC) of rhesus monkeys while they listened to a novel vocalization and repeated presentations of the same vocalization. We found that the cross-frequency coupling between the gamma-band amplitude and theta-band phase of the LFP was modulated by repeated presentations of a stimulus. During the first (novel) presentation of a stimulus, gamma-band activity was modulated by the theta-band phase. However, with repeated presentations of the same stimulus, this cross-frequency coupling was attenuated. These results suggest that cross-frequency coupling may play a role in the neural computations that underlie the differentiation between novel and repeated stimuli in the vPFC.
vocalization; rhesus monkey; neural oscillation; theta band; gamma band
The ventral hippocampus, unlike its dorsal counterpart, is required for anxiety-like behavior. The means by which it acts are unknown. We hypothesized that the hippocampus synchronizes with downstream targets that influence anxiety, such as the medial prefrontal cortex (mPFC). To test this hypothesis, we recorded mPFC and hippocampal activity in mice exposed to two anxiogenic arenas. Theta-frequency activity in the mPFC and ventral, but not dorsal hippocampus was highly correlated at baseline, and this correlation increased in both anxiogenic environments. Increases in mPFC theta power predicted avoidance of the aversive compartments of each arena, and were larger in serotonin 1A-receptor knockout mice, a genetic model of increased anxiety-like behavior. These results suggest a role for theta-frequency synchronization between the ventral hippocampus and the mPFC in anxiety. They are consistent with the notion that such synchronization is a general mechanism by which the hippocampus communicates with downstream structures of behavioral relevance.
Neural correlates of aging in the medial prefrontal cortex (mPFC) were studied using an operant delayed response task. The task used blocks of trials with memory (delayed alternation) and visually guided (stimulus-response) responding. Older rats (24 mo) performed at a slow pace compared to younger rats (6 mo). They wasted time engaged in non-essential behaviors (e.g. licking on spouts beyond the period of reward delivery) and were slow to respond at the end of the delay period. Aged mPFC neurons showed normal spatial processing. They differed from neurons in younger rats by having reduced modulations by imperative stimuli indicating reward availability and reduced activity associated with response latencies for reward collection. Older rats showed reduced sensitivity to imperative stimuli at three levels of neural activity: reduced fractions of neurons with changes in firing rate around the stimulus, reduced correlation over neurons at the time of the stimulus as measured with analysis of population activity, and reduced amplitudes of event-related fluctuations in intracortical field potentials at the time of the imperative stimulus. Our findings suggest that aging alters the encoding of time-sensitive information and impairs the ability of prefrontal networks to keep subjects “on task”.
Sub-regions of prefrontal cortex are important for estimating reward values and using these values to guide behavior. The present studies directly tested whether orbital (O-PFC) and lateral (L-PFC) prefrontal cortex are necessary for evaluating trial-to-trial changes in the reward values predicted by visual cues. We have compared intact rhesus monkeys, those with bilateral O-PFC lesions (n=3), and those with bilateral L-PFC lesions (n=3). We used three versions of a visually-cued color-discrimination task: we varied reward size, delay-to-reward, or both. O-PFC lesions altered estimations of predicted reward value in all versions of the task. L-PFC lesions disrupted performance only when both reward size and delay-to-reward were varied together. Neither lesion directly affected basic internal drive states (satiation curves). Our results suggest that O-PFC is essential for establishing independent, context-specific scales with which predicted reward values are measured. L-PFC appears necessary for integration of predicted reward value across these different scales.
Motivation; Emotion; Macaque; Reinforcement; Decision
Flexible control of behavior depends on the representation, maintenance and updating of context information in working memory, which is thought to rely on prefrontal cortex (PFC). However, in contrast to maintenance, the dynamics of context activation and updating have not been well studied. To identify neural signals associated with context updating, we compared event-related potentials associated with cues that did or did not provide task-relevant context information. The earliest effect of context was detected 200 ms following cue onset and had a scalp topography consistent with a generator in PFC. Subsequent effects of context were detected at 400 - 700 ms following cue onset (P3b), with a broad scalp distribution spanning posterior areas, and during the final 300 ms preceding the target, with a probable generator in medial frontal cortex. We propose that the effect of context on P2 is consistent with the onset of context updating in PFC. Subsequent components may be indicative of activation of task-relevant posterior regions and context maintenance.
Anatomical and functional studies of the prefrontal cortex (PFC) have identified multiple PFC subregions. We argue that the PFC is involved in cognitive functions exceeding the sum of specific functions attributed to its subregions. These can be revealed either by lesions of the whole PFC, or more specifically by selective disconnection of the PFC from certain types of information (for example, visual) allowing the investigation of PFC function in toto. Recent studies in macaque monkeys using the latter approach lead to a second conclusion: that the PFC, as a whole, could be fundamentally specialized for representing events that are extended in time. The representation of temporally complex events might underlie PFC involvement in general intelligence, decision-making, and executive function.
This study investigates the interaction between brain lesion location and monoamine oxidase A (MAO-A) in the genesis of aggression in patients with penetrating traumatic brain injury (PTBI).
We enrolled 155 patients with PTBI and 42 controls drawn from the Vietnam Head Injury Study registry. Patients with PTBI were divided according to lesion localization (prefrontal cortex [PFC] vs non-PFC) and were genotyped for the MAO-A polymorphism linked to low and high transcriptional activity. Aggression was assessed with the aggression/agitation subscale of the Neuropsychiatric Inventory (NPI-a).
Patients with the highest levels of aggression preferentially presented lesions in PFC territories. A significant interaction between MAO-A transcriptional activity and lesion localization on aggression was revealed. In the control group, carriers of the low-activity allele demonstrated higher aggression than high-activity allele carriers. In the PFC lesion group, no significant differences in aggression were observed between carriers of the 2 MAO-A alleles, whereas in the non-PFC lesion group higher aggression was observed in the high-activity allele than in the low-activity allele carriers. Higher NPI-a scores were linked to more severe childhood psychological traumatic experiences and posttraumatic stress disorder symptomatology in the control and non-PFC lesion groups but not in the PFC lesion group.
Lesion location and MAO-A genotype interact in mediating aggression in PTBI. Importantly, PFC integrity is necessary for modulation of aggressive behaviors by genetic susceptibilities and traumatic experiences. Potentially, lesion localization and MAO-A genotype data could be combined to develop risk-stratification algorithms and individualized treatments for aggression in PTBI.
The psychological processes of doubting and skepticism have recently become topics of neuroscientific investigation. In this context, we developed the False Tagging Theory, a neurobiological model of the belief and doubt process, which proposes that the prefrontal cortex is critical for normative doubt regarding properly comprehended cognitive representations. Here, we put our theory to an empirical test, hypothesizing that patients with prefrontal cortex damage would have a doubt deficit that would manifest as higher authoritarianism and religious fundamentalism.
Ten patients with bilateral damage to the ventromedial prefrontal cortex (vmPFC), ten patients with damage to areas outside the vmPFC, and sixteen medical comparison patients, who experienced life-threatening (but non-neurological) medical events, completed a series of scales measuring authoritarianism, religious fundamentalism, and specific religious beliefs.
VMPFC patients reported significantly higher authoritarianism and religious fundamentalism than the other groups. The degrees of authoritarianism and religious fundamentalism in the vmPFC group were significantly higher than normative values, as well; by contrast, the comparison groups did not differ from normative values. Moreover, vmPFC patients reported increased specific religious beliefs after brain injury.
The findings support the False Tagging Theory, and suggest that the vmPFC is critical for psychological doubt and resistance to authoritarian persuasion.
lesion; prefrontal cortex; authoritarianism; fundamentalism; belief
Recent studies show that glutamate and orexin (ORX, also known as hypocretin) inputs to the ventral tegmental area (VTA) dopamine (DA) cell region are essential for conditioned behavioral responses to reward-associated stimuli. In vitro experiments showed that ORX inputs to VTA potentiate responses of DA neurons to glutamate inputs, but it has remained unclear which glutamate inputs are modulated by ORX. The medial prefrontal cortex (mPFC) is a good candidate, given its role in processing complex stimulus-response information and its reciprocal connections with VTA DA neurons. Here we used in vivo recordings in anesthetized rats to investigate the responses of VTA DA neurons to mPFC stimulation, and how these responses are modulated by ORX. We demonstrate that mPFC stimulation evokes short- and long-latency excitation and inhibition in DA neurons. Maximal short-latency excitatory responses originated from stimulation sites in ventral prelimibic/infralimbic cortex, and were significantly more frequent during the active compared to the rest period of the diurnal cycle. Application of ORX onto VTA DA neurons increased baseline activity and augmented or revealed excitatory responses to mPFC stimulation independent of changes in baseline activity, and without consistently affecting inhibitory responses. Moreover, orexin-1 receptor antagonism decreased tonic DA cell activity in active- but not rest-period animals, confirming a diurnal influence of ORX. These results indicate that ORX potently influences DA neuron activity, in part by modulating receptivity to mPFC inputs. By regulating prefrontal control of DA release, ORX projections to VTA may shape motivated behaviors in response to conditioned stimuli.
extracellular recording; electrical stimulation; dopamine; orexin/hypocretin; SB334867; circadian