Orbitomedial prefrontal cortical projections to hypothalamus in the rat

A previous study in the rat revealed that distinct orbital and medial prefrontal cortical (OMPFC) areas projected to specific columns of the midbrain periaqueductal gray region (PAG). This study used anterograde tracing techniques to define projections to the hypothalamus arising from the same OMPFC regions. In addition, injections of anterograde and retrograde tracers were made into different PAG columns to examine connections between hypothalamic regions and PAG columns projected upon by the same OMPFC regions. The most extensive patterns of hypothalamic termination were seen after injection of anterograde tracer in prelimbic and infralimbic (PL/IL) and the ventral and medial orbital (VO/MO) cortices. Projections from rostral PL/IL and VO/MO targeted the rostrocaudal extent of the lateral hypothalamus, as well as lateral perifornical, and dorsal and posterior hypothalamic areas. Projections arising from caudal PL/IL terminated within the dorsal hypothalamus, including the dorsomedial nucleus and dorsal and posterior hypothalamic areas. There were also projections to medial perifornical and lateral hypothalamic areas. In contrast, it was found that anterior cingulate (AC), dorsolateral orbital (DLO), and agranular insular (AId) cortices projected to distinct and restricted hypothalamic regions. Projections arising from AC terminated within dorsal and posterior hypothalamic areas, whereas DLO and AId projected to the lateral hypothalamus. The same OMPFC regions also projected indirectly, by means of specific PAG columns, to many of the same hypothalamic fields. In the context of our previous findings, these data indicate that, in both rat and macaque, parallel but distinct circuits interconnect OMPFC areas with specific hypothalamic regions, as well as PAG columns.     

Magnetic stimulation of the dorsolateral prefrontal cortex dissociates fragile visual short-term memory from visual working memory

To guide our behavior in successful ways, we often need to rely on information that is no longer in view, but maintained in visual short-term memory (VSTM). While VSTM is usually broken down into iconic memory (brief and high-capacity store) and visual working memory (sustained, yet limited-capacity store), recent studies have suggested the existence of an additional and intermediate form of VSTM that depends on activity in extrastriate cortex. In previous work, we have shown that this fragile form of VSTM can be dissociated from iconic memory. In the present study, we provide evidence that fragile VSTM is different from visual working memory as magnetic stimulation of the right dorsolateral prefrontal cortex (DLPFC) disrupts visual working memory, while leaving fragile VSTM intact. In addition, we observed that people with high DLPFC activity had superior working memory capacity compared to people with low DLPFC activity, and only people with high DLPFC activity really showed a reduction in working memory capacity in response to magnetic stimulation. Altogether, this study shows that VSTM consists of three stages that have clearly different characteristics and rely on different neural structures. On the methodological side, we show that it is possible to predict individual susceptibility to magnetic stimulation based on functional MRI activity.     

Altered connectivity between prefrontal and sensorimotor cortex in conversion paralysis

Conversion paralysis (CP) is a frequent and impairing psychiatric disorder, affecting voluntary motor function. Yet, we have previously shown that the motor system of CP patients with a unilateral conversion paresis is recruited to a similar degree during imagined movements of the affected and unaffected limb. In contrast, imagery of movements with the affected limb results in larger prefrontal activation. It remains unclear how this hand-specific increased prefrontal activity relates to the reduced responsiveness of motor and somatosensory areas, a consistent and important feature of CP patients.In the current study, we investigated changes in the inter-regional coupling between prefrontal cortex (PFC) and sensorimotor regions when CP patients imagined movements involving either the affected or the unaffected hand. We found that there were distinct connectivity patterns for different parts of the PFC. While ventromedial PFC was not functionally connected to the motor system, we observed strong functional coupling between the dorsolateral PFC and various sensorimotor areas. Furthermore, this coupling was modulated by whether patients imagined movements of their affected or unaffected hand. Together, these results suggest that the reduced motor responsitivity observed in CP may be linked to altered dorsolateral prefrontal-motor connectivity.     

Comparison of deficits in electrical self-stimulation after ibotenic acid lesion of the lateral hypothalamus and the medial prefrontal cortex

The aim of the present study was to compare the self-stimulation deficit produced by a unilateral injection of the neurotoxin, ibotenic acid, in the lateral hypothalamus (LH) to the deficit produced by the same unilateral injection in the medial prefrontal cortex (MPC). Four groups of adult male Sprague-Dawley rats were used: in two control groups, electrodes were bilaterally implanted in the LH (5 rats) or in the MPC (6 rats) and self-stimulation (ICSS) was obtained separately with the right and left electrodes. In the two experimental groups the intrinsic neurons of the LH (8 rats) or of the MPC (10 rats) were destroyed unilaterally by local injection of ibotenic acid (4 micrograms in 0.5 microliter); the other side served as the sham-lesioned control. Ten days later ICSS electrodes were implanted bilaterally, one in the lesioned area, the other in the contralateral region. As in the case of the control rats, ICSS was determined separately for each electrode, first by a rate dependent test (nose-poke) then by a 'rate-free' test (shuttle-box). In the LH and MPC control rats, ICSS responses were the same with stimulation on either side. In the LH-lesioned rats, the ICSS rates measured with the nose-poke test were significantly decreased with stimulation on the lesioned side, whereas rates with stimulation of the non-lesioned LH were normal. Likewise, while shuttle responses with stimulation of the non-lesioned LH were normal, the OFF-time was increased and the ON-time was decreased with stimulation of the lesioned LH. In the MPC-lesioned rats, ICSS (nose-poke) was totally suppressed and the shuttle responses were disorganized since neither the ON- nor the OFF-times changed in response to increasing current intensities. Nose-poke responses with stimulation of the non-lesioned MPC were just about normal. These results show that in the two brain regions studied local neurons are involved in ICSS. The difference in the magnitude of the deficit observed suggests, that the neuronal circuits involved in MPC self-stimulation are poorly represented whereas in the LH many neuronal circuits involved in these mechanisms overlap.     

Selective activation of the ventrolateral prefrontal cortex in the human brain during active retrieval processing

The present study examined the role of the prefrontal cortex in retrieval processing using functional magnetic resonance imaging in human subjects. Ten healthy subjects were scanned while they performed a task that required retrieval of specific aspects of visual information. In order to examine brain activity specifically associated with retrieval, we designed a task that had retrieval and control conditions that were perfectly matched in terms of depth of encoding, decision making and postretrieval monitoring and differed only in terms of whether retrieval was required. In the retrieval condition, based on an instructional cue, the subjects had to retrieve either the particular stimulus that was previously presented or its location. In the control condition, the cue did not instruct retrieval but shared with the instructional cues the function of alerting the subjects of the impending test phase. The comparison of activity between the retrieval and control conditions demonstrated a significant and selective increase in activity related to retrieval processes within the ventrolateral prefrontal cortical region, more specifically within area 47/12. These activity increases were bilateral but stronger in the right hemisphere. The present study by strictly controlling the level of encoding, postretrieval monitoring, and decision making has demonstrated a specific increase in the ventrolateral prefrontal region that could be clearly related to active retrieval processing, i.e. the active selection of particular stored visual representations.     

Bilateral decrease in ventrolateral prefrontal cortex activation during motor response inhibition in mania

Mania has been frequently associated with impaired inhibitory control. The present study aimed to identify brain functional abnormalities specifically related to motor response inhibition in mania by using event-related fMRI in combination with a Go/NoGo task designed to control for extraneous cognitive processes involved in task performance. Sixteen manic patients and 16 healthy subjects, group-matched for age and sex, were imaged while performing a warned equiprobable Go/NoGo task during event-related fMRI. Between-group differences in brain activation associated with motor response inhibition were assessed using analyses of covariance. Although no significant between-group differences in task performance accuracy were observed, patients showed significantly longer response times on Go trials. After controlling for covariates, the only brain region that differentiated the two groups during motor response inhibition was the ventrolateral prefrontal cortex (VLPFC), where activation was significantly decreased in both the right and left hemispheres in manic patients. Our data suggest that response inhibition in mania is associated with a lack of engagement of the bilateral VLPFC, which is known to play a primary role in the suppression of irrelevant responses. This result might give clues to understanding the pathophysiology of dishinhibition and impulsivity that characterize mania.     

Chronic vagus nerve stimulation for treatment-resistant depression increases regional cerebral blood flow in the dorsolateral prefrontal cortex

The purpose of the present study was to assess the effects of vagus nerve stimulation (VNS) therapy on regional cerebral blood flow (rCBF) in depressed patients. Regional cerebral blood flow (rCBF) was assessed by [^99mTc]-HMPAO-single photon emission computed tomography (SPECT) before and after 10 weeks of VNS in patients participating in an open, uncontrolled European multi-center study investigating efficacy and safety of VNS. Patients suffered from major depression, with a baseline score of ≥ 20 on the 24-item Hamilton Depression Rating Scale (HDRS) and had been unsuccessfully treated with at least two adequately prescribed antidepressant drugs. Data of 15 patients could be analyzed using SPM 2. After 10 weeks of VNS (20 Hz, 500 μs pulse width, stimulation during 30 s every 5 min at the maximal comfortable level) rCBF was increased in the left dorsolateral/ventrolateral prefrontal cortex (Brodmann areas 46 and 47) and decreased in the right posterior cingulate area, the lingual gyrus and the left insula. Our findings are in line with earlier results which showed that VNS increases rCBF in the left dorsolateral prefrontal cortex. The modulation of the activity in this region could be associated with the antidepressant efficacy of VNS.     

Footshock stress facilitates self-stimulation of the medial prefrontal cortex but not the lateral hypothalamus in the rat

The effects of stress on self-stimulation were investigated by exposing rats to either controllable, uncontrollable or no footshock. Both controllable and uncontrollable footshock increased medial prefrontal cortex self-stimulation rates immediately as well as 24 h following treatment. Controllable footshock produced a greater enhancement than uncontrollable footshock. In contrast, self-stimulation of the lateral hypothalamus was unaffected by either footshock treatment. These results are interpreted with reference to the neurochemical response of the mesocortical dopaminergic system to acute stress.     

Spatial and temporal distribution of visual information coding in lateral prefrontal cortex

Prefrontal neurons code many kinds of behaviourally relevant visual information. In behaving monkeys, we used a cued target detection task to address coding of objects, behavioural categories and spatial locations, examining the temporal evolution of neural activity across dorsal and ventral regions of the lateral prefrontal cortex (encompassing parts of areas 9, 46, 45A and 8A), and across the two cerebral hemispheres. Within each hemisphere there was little evidence for regional specialisation, with neurons in dorsal and ventral regions showing closely similar patterns of selectivity for objects, categories and locations. For a stimulus in either visual field, however, there was a strong and temporally specific difference in response in the two cerebral hemispheres. In the first part of the visual response (50–250 ms from stimulus onset), processing in each hemisphere was largely restricted to contralateral stimuli, with strong responses to such stimuli, and selectivity for both object and category. Later (300–500 ms), responses to ipsilateral stimuli also appeared, many cells now responding more strongly to ipsilateral than to contralateral stimuli, and many showing selectivity for category. Activity on error trials showed that late activity in both hemispheres reflected the animal's final decision. As information is processed towards a behavioural decision, its encoding spreads to encompass large, bilateral regions of prefrontal cortex.     

Role of bar press-related neurons in the dorsolateral prefrontal cortex during task performance by monkey

Extracellular single neuron activity of the dorsolateral prefrontal cortex (DL) was recorded in the monkey, during bar pressing for reward. The bar press-related neurons which exhibited excitation or inhibition during the bar press period were found to be scattered diffusely in the DL. Activity changes that arose during the bar press period also appeared when the experimenter pressed the bar for the monkey. When delivery of food was delayed for a random time after cue tone on, bar press responses were still confined to the bar press period and did not extend beyond the cue tone. These results, together with the lesion studies, suggest that bar press-related neurons are involved in the animal's concentration during the bar press period.     

Storm in a coffee cup: caffeine modifies brain activation to social signals of threat

Caffeine, an adenosine A₁ and A_2A receptor antagonist, is the most popular psychostimulant drug in the world, but it is also anxiogenic. The neural correlates of caffeine-induced anxiety are currently unknown. This study investigated the effects of caffeine on brain regions implicated in social threat processing and anxiety. Participants were 14 healthy male non/infrequent caffeine consumers. In a double-blind placebo-controlled crossover design, they underwent blood oxygenation level-dependent functional magnetic resonance imaging (fMRI) while performing an emotional face processing task 1 h after receiving caffeine (250 mg) or placebo in two fMRI sessions (counterbalanced, 1-week washout). They rated anxiety and mental alertness, and their blood pressure was measured, before and 2 h after treatment. Results showed that caffeine induced threat-related (angry/fearful faces > happy faces) midbrain-periaqueductal gray activation and abolished threat-related medial prefrontal cortex wall activation. Effects of caffeine on extent of threat-related amygdala activation correlated negatively with level of dietary caffeine intake. In concurrence with these changes in threat-related brain activation, caffeine increased self-rated anxiety and diastolic blood pressure. Caffeine did not affect primary visual cortex activation. These results are the first to demonstrate potential neural correlates of the anxiogenic effect of caffeine, and they implicate the amygdala as a key site for caffeine tolerance.     

Individual differences in moral judgment competence are related to activity of the prefrontal cortex when attributing blame to evil intention

The weighing of intentions and consequences is inconsistent in adult’s moral judgments, and this is particularly prominent when assigning blame to the immoral intentions in the absence of negative outcomes. The current study extends previous research by examining how individual differences in moral judgment competence are reflected in the cortical network when making judgments about immoral intentions. Twenty-four participants were scanned, using functional magnetic resonance imaging, while making judgments about three kinds of moral scenarios: a neutral condition, an immoral intention condition, and an immoral condition. The result showed that comparing with making judgments about the other two conditions, making judgments about the immoral intentions takes longer time and was associated with significantly elevated activity in the dorsolateral prefrontal cortex and the ventrolateral prefrontal cortex. Additionally, moral judgment competence scores were inversely correlated with activity in the right dorsolateral prefrontal cortex when assigning blame to the immoral intentions. Greater activity in the right dorsolateral prefrontal cortex in participants with lower moral judgment competence possibly reflected increased recruitment of cognitive resource applied to control impulsive response and integrate competitive information in making judgments about the immoral intention.     

Prefrontal cortex activity is reduced in gambling and nongambling substance users during decision-making

OBJECTIVE: Poor decision-making is a hallmark of addiction, whether to substances or activities. Performance on a widely used test of decision-making, the Iowa Gambling Task (IGT), can discriminate controls from persons with ventral medial frontal lesions, substance-dependence, and pathological gambling. Positron emission tomography (PET) studies indicate that substance-dependent individuals show altered prefrontal activity on the task. Here we adapted the IGT to an fMRI setting to test the hypothesis that defects in ventral medial and prefrontal processing are associated with impaired decisions that involve risk but may differ depending on whether substance dependence is comorbid with gambling problems. METHOD: 18 controls, 14 substance-dependent individuals (SD), and 16 SD with gambling problems (SDPG) underwent fMRI while performing a modified version of the IGT. RESULT: Group differences were observed in ventral medial frontal, right frontopolar, and superior frontal cortex during decision-making. Controls showed the greatest activity, followed by SDPG, followed by SD. CONCLUSION: Our results support a hypothesis that defects in ventral medial frontal processing lead to impaired decisions that involve risk. Reductions in right prefrontal activity during decision-making appear to be modulated by the presence of gambling problems and may reflect impaired working memory, stimulus reward valuation, or cue reactivity in substance-dependent individuals.     

Linking trait-based phenotypes to prefrontal cortex activation during inhibitory control

Inhibitory control is subserved in part by discrete regions of the prefrontal cortex whose functionality may be altered according to specific trait-based phenotypes. Using a unified model of normal range personality traits, we examined activation within lateral and medial aspects of the prefrontal cortex during a manual go/no-go task. Evoked hemodynamic oxygenation within the prefrontal cortex was measured in 106 adults using a 16-channel continuous-wave functional near-infrared spectroscopy system. Within lateral regions of the prefrontal cortex, greater activation was associated with higher trait levels of extraversion, agreeableness and conscientiousness, and lower neuroticism. Higher agreeableness was also related to more activation in the medial prefrontal cortex during inhibitory control. These results suggest that personality traits reflecting greater emotional stability, extraversion, agreeableness and conscientiousness may be associated with more efficient recruitment of control processes subserved by lateral regions of the prefrontal cortex. These findings highlight key links between trait-based phenotypes and neural activation patterns in the prefrontal cortex underlying inhibitory control.     

In-group as part of the self: In-group favoritism is mediated by medial prefrontal cortex activation

Abstract

Our identity consists of knowledge about our individual attributes (personal identity) as well as knowledge about our shared attributes derived from our membership in certain social groups (social identity). As individuals seek to achieve a positive self-image, they aim at comparing favorably with other individuals or their in-group comparing favorably with referent out-groups. Imaging data suggest a network centered on the medial prefrontal cortex (MPFC) to instantiate functions that are integral to the self, conceived as the personal self. Given that the social self is constituted by the same mechanisms as the personal self, we expect MPFC activation also for situations in which the social self is addressed, for instance when situations permit evaluative intergroup comparisons. Accordingly, participants worked on a modified version of the minimal group paradigm in the present functional magnetic resonance imaging experiment. Imaging data revealed activation within a network centered on the dorsal MPFC specifically for social identity processes. Furthermore, this activation showed correlation with the displayed in-group bias. The present findings show that social and personal identity processes draw on the same cerebral correlates and hence it is concluded that a network centered on the MPFC subserves functions integral to the self.     

Strong correspondence between prefrontal and visual representations during emotional perception

Emotion is thought to cause focal enhancement or distortion of certain components of memory, indicating a complex property of emotional modulation on memory rather than simple enhancement. However, the neural basis for detailed modulation of emotional memory contents has remained unclear. Here has been shown that the information processing of the prefrontal cortex differentially affects sensory representations during experience of emotional information compared with neutral information, using functional magnetic resonance imaging (fMRI). It was found that during perception of emotional pictures, information representation in primary visual cortex (V1) significantly corresponded with the representations in dorsolateral prefrontal cortex (dlPFC). This correspondence was not observed for neutral pictures. Furthermore, participants with greater correspondence between visual and prefrontal representations showed better memory for high‐level semantic components but not for low‐level visual components of emotional stimuli. These results suggest that sensory representation during experience of emotional stimuli, compared with neutral stimuli, is more directly influenced by internally generated higher‐order information from the prefrontal cortex.     

Age-related valence-based reversal in recruitment of medial prefrontal cortex on a visual search task

Previous behavioral research has revealed a positivity effect that occurs with aging, with older adults focusing more on positive information and less on negative emotional stimuli as compared to young adults. Questions have been raised as to whether this effect exists in the rapid detection of information or whether it operates only at later stages of processing. In the present study, we used eye-tracking and neuroimaging methodologies to examine whether the two age groups accomplished the detection of emotional information on a visual search task using the same mechanisms. Eye-tracking results revealed no significant age differences in detection or viewing time of emotional targets as a function of valence. Despite their general similarity in task performance, neuroimaging results revealed an age-related valence-based reversal in medial prefrontal cortex (MPFC) activity, with detection of negative compared to positive targets activating the MPFC more for younger adults, and detection of positive compared to negative targets activating the MPFC more for older adults. These results suggest that age-related valence reversals in neural activity can exist even on tasks that require only relatively automatic processing of emotional information.     

Negative emotions impact lateral prefrontal cortex activation during theory of mind: An fNIRS study

The lateral prefrontal cortex (lPFC) plays a critical role in inhibiting self-perspective information, which is necessary for theory of mind (ToM) processing. Additionally, previous research has indicated that negative emotions interfere with lPFC activation during executive tasks. In this study, we hypothesized that negative emotions would inhibit lPFC activation during a ToM task. While female participants performed the director task following the observation of emotionally laden movies (neutral/negative/positive), their prefrontal hemodynamic activity was measured using near-infrared spectroscopy. After viewing the neutral movie, bilateral lPFC activity was significantly enhanced during ToM process compared to the control condition. In contrast, after viewing the negative movie, left lPFC activity during ToM process was significantly impaired. These results were interpreted to support the idea that negative emotions interfere with inhibition of self-perspective information through inactivation of the lPFC.     

Improving working memory: Exploring the effect of transcranial random noise stimulation and transcranial direct current stimulation on the dorsolateral prefrontal cortex

Objective

The aim of this study was to determine if working memory (WM) performance is significantly improved after the delivery of transcranial random noise stimulation (tRNS) to the left dorsolateral prefrontal cortex (DLPFC), compared to an active comparator or sham.

Methods

Ten participants undertook three experimental sessions in which they received 10 min of anodal tDCS (active comparator), tRNS or sham tDCS whilst performing the Sternberg WM task. Intra-stimulation engagement in a WM task was undertaken as this has been previously shown to enhance the effects of tDCS. Experimental sessions were separated by a minimum of 1 week. Immediately prior to and after each stimulation session the participants were measured on speed and accuracy of performance on an n-back task.

Results

There was significant improvement in speed of performance following anodal tDCS on the 2-back WM task; this was the only significant finding.

Conclusions

The results do not provide support for the hypothesis that tRNS improves WM. However, the study does provide confirmation of previous findings that anodal tDCS enhances some aspects of DLPFC functioning. Methodological limitations that may have contributed to the lack of significant findings following tRNS are discussed.

Significance

Anodal tDCS may have significant implications for WM remediation in psychiatric conditions, particularly schizophrenia.     

dcc orchestrates the development of the prefrontal cortex during adolescence and is altered in psychiatric patients

Adolescence is a period of heightened susceptibility to psychiatric disorders of medial prefrontal cortex (mPFC) dysfunction and cognitive impairment. mPFC dopamine (DA) projections reach maturity only in early adulthood, when their control over cognition becomes fully functional. The mechanisms governing this protracted and unique development are unknown. Here we identify dcc as the first DA neuron gene to regulate mPFC connectivity during adolescence and dissect the mechanisms involved. Reduction or loss of dcc from DA neurons by Cre-lox recombination increased mPFC DA innervation. Underlying this was the presence of ectopic DA fibers that normally innervate non-cortical targets. Altered DA input changed the anatomy and electrophysiology of mPFC circuits, leading to enhanced cognitive flexibility. All phenotypes only emerged in adulthood. Using viral Cre, we demonstrated that dcc organizes mPFC wiring specifically during adolescence. Variations in DCC may determine differential predisposition to mPFC disorders in humans. Indeed, DCC expression is elevated in brains of antidepressant-free subjects who committed suicide.