Orbitomedial Prefrontal Cortex Research Articles

Chemogenetic inactivation of the nucleus reuniens and its projections to the orbital cortex produce deficits on discrete measures of behavioral flexibility in the attentional set-shifting task

The nucleus reuniens (RE) of the ventral midline thalamus is a critical node in the communication between the orbitomedial prefrontal cortex (OFC) and the hippocampus (HF). While RE has been shown to directly participate in memory-associated functions through its connections with the medial prefrontal cortex and HF, less is known regarding the role of RE in executive functioning. Here, we examined the involvement of RE and its projections to the orbital cortex (ORB) in attention and behavioral flexibility in male rats using the attentional set shifting task (AST). Rats expressing the hM4Di DREADD receptor in RE were implanted with indwelling cannulas in either RE or the ventromedial ORB to pharmacologically inhibit RE or its projections to the ORB with intracranial infusions of clozapine-N-oxide hydrochloride (CNO). Chemogenetic-induced suppression of RE resulted in impairments in reversal learning and set-shifting. This supports a vital role for RE in behavioral flexibility – or the ability to adapt behavior to changing reward or rule contingencies. Interestingly, CNO suppression of RE projections to the ventromedial ORB produced impairments in rule abstraction – or dissociable effects elicited with direct RE suppression. In summary, the present findings indicate that RE, mediated in part by actions on the ORB, serves a critical role in the flexible use of rules to drive goal directed behavior. The cognitive deficits of various neurological disorders with impaired communication between the HF and OFC, may be partly attributed to alterations of RE -- as an established intermediary between these cortical structures.

Auditory verbal hallucination can be evoked by prefrontal epileptic seizure

Auditory verbal hallucinations (AVHs) have been reported in neocortical temporal epileptic seizures and have been considered highly associated with implication of auditory cortex by epileptic discharges or electrical stimulation. Herein, we report two rare frontal epilepsy cases in which AVHs featured the habitual seizures. The epileptogenic zones of these two patients were localized in the dorsal and orbitomedial prefrontal cortex, respectively by stereoelectroencephalography (SEEG) monitoring. Comparing with the AVHs in schizophrenia, we postulated that the phenomenological similarities between the two sets of AVHs imply homology in mechanisms. Ictal SEEG confirmed that the wide involvement of prefrontal–cingulate–auditory cortical network by low-voltage fast activity corresponded the occurrence with AVHs during frontal epileptic seizures. Electrical stimulation study of one of the two cases highlighted the causal role of prefrontal–cingulate cortex in the emergence of AVHs. Based on our clinical observation, SEEG findings, and electrical cortical stimulation, we supposed that wide implication of prefrontal–cingulate–auditory cortical network during epileptic seizure underlie the emergence of AVHs, and further hypothesized that AVHs could be yielded by transient deficit of self-monitoring for inner speech in focal epileptic seizures.

Neuroimaging Correlates of Depression-Implications to Clinical Practice.

The growth of the literature about neuroimaging of major depressive disorder (MDD) over the last several decades has contributed to the progress in recognizing precise brain areas, networks, and neurotransmitter processes related to depression. However, there are still doubts about the etiology and pathophysiology of depression that need answering. The authors did a nonsystematic review of the literature using PubMed database, with the following search terms: “major depressive disorder,” “neuroimaging,” “functional imaging,” “magnetic resonance imaging,” “functional magnetic resonance imaging,” and “structural imaging,” being selected the significant articles published on the topic. Anterior cingulate cortex, hippocampus, orbitomedial prefrontal cortex, amygdala basal ganglia, and the cerebellum were the main affected areas across the selected studies. These areas respond to particular neurotransmitter systems, neurochemicals, hormones, and other signal proteins; even more, the evidence supports a distorted frontolimbic mood regulatory pathway in MDD patients. Despite the positive findings, translation to treatment of MDD remains illusory. In conclusion, this article aims to be a critical review of the neuroimaging correlates of depression in clinical research with the purpose to improve clinical practice.

Finding the Sweet Spot: Fine-Tuning DBS Parameters to Cure Seizures While Avoiding Psychiatric Complications.

Reversible Psychiatric Adverse Effects Related to Deep Brain Stimulation of the Anterior Thalamus in Patients With Refractory Epilepsy Järvenpää S, Peltola J, Rainesalo S, et al. Epilepsy Behav. 2018;88:373-379. doi:10.1016/j.yebeh.2018.09.006Objective:Anterior nucleus of thalamus (ANT) deep brain stimulation (DBS) is becoming a more common treatment for drug-resistant epilepsy. Epilepsy and depression display a bidirectional association. Anterior nucleus of thalamus has connections to anterior cingulate cortex and orbitomedial prefrontal cortex, hence, a possible role in emotional and executive functions, and thus, ANT DBS might exert psychiatric adverse effects. Our aim was to evaluate previous and current psychiatric symptoms in patients with epilepsy undergoing ANT DBS surgery and assess the predictability of psychiatric adverse effects. Programming-related psychiatric adverse effects are also reported.Method:Twenty-two patients with ANT DBS for retractable epilepsy were examined, and a psychiatric evaluation of depressive and other psychiatric symptoms was performed with Montgomery-Åsberg Depression Rating Scale, Beck Depression Inventory, and Symptom Checklist prior to surgery, concentrating on former and current psychiatric symptoms and medications. The follow-up visit was 1 year after surgery.Results:At the group level, no changes in mood were observed during ANT DBS treatment. Two patients with former histories of depression experienced sudden depressive symptoms related to DBS programming settings; these were quickly alleviated after changing the stimulation parameters. In addition, 2 patients with no previous histories of psychosis gradually developed clear paranoid and anxiety symptoms that also relieved slowly after changing the programming settings.Conclusion:The majority of our ANT DBS patients did not experience psychiatric adverse effects. Certain DBS parameters might predispose to sudden depressive or slowly manifesting paranoid symptoms that are reversible via programming changes.

Reversible psychiatric adverse effects related to deep brain stimulation of the anterior thalamus in patients with refractory epilepsy

ObjectiveAnterior nucleus of thalamus (ANT) deep brain stimulation (DBS) is becoming a more common treatment for drug-resistant epilepsy. Epilepsy and depression display a bidirectional association. Anterior nucleus of thalamus has connections to anterior cingulate cortex and orbitomedial prefrontal cortex, hence, a possible role in emotional and executive functions, and thus, ANT DBS might exert psychiatric adverse effects. Our aim was to evaluate previous and current psychiatric symptoms in patients with epilepsy undergoing ANT DBS surgery and assess the predictability of psychiatric adverse effects. Programming-related psychiatric adverse effects are also reported. MethodTwenty-two patients with ANT DBS for retractable epilepsy were examined, and a psychiatric evaluation of depressive and other psychiatric symptoms was performed with Montgomery and Åsberg Depression Rating Scale (MADRS), Beck Depression Inventory (BDI), and Symptom Checklist prior to surgery, concentrating on former and current psychiatric symptoms and medications. The follow-up visit was one year after surgery. ResultsAt the group level, no changes on mood were observed during ANT DBS treatment. Two patients with former histories of depression experienced sudden depressive symptoms related to DBS programming settings; these were quickly alleviated after changing the stimulation parameters. In addition, two patients with no previous histories of psychosis gradually developed clear paranoid and anxiety symptoms that also relieved slowly after changing the programming settings. ConclusionThe majority of our ANT DBS patients did not experience psychiatric adverse effects. Certain DBS parameters might predispose to sudden depressive or slowly manifesting paranoid symptoms that are reversible via programming changes.

Neuronal connectivity in major depressive disorder: a systematic review.

BackgroundThe causes of major depressive disorder (MDD), as one of the most common psychiatric disorders, still remain unclear. Neuroimaging has substantially contributed to understanding the putative neuronal mechanisms underlying depressed mood and motivational as well as cognitive impairments in depressed individuals. In particular, analyses addressing changes in interregional connectivity seem to be a promising approach to capture the effects of MDD at a systems level. However, a plethora of different, sometimes contradicting results have been published so far, making general conclusions difficult. Here we provide a systematic overview about connectivity studies published in the field over the last decade considering different methodological as well as clinical issues.MethodsA systematic review was conducted extracting neuronal connectivity results from studies published between 2002 and 2015. The findings were summarized in tables and were graphically visualized.ResultsThe review supports and summarizes the notion of an altered frontolimbic mood regulation circuitry in MDD patients, but also stresses the heterogeneity of the findings. The brain regions that are most consistently affected across studies are the orbitomedial prefrontal cortex, anterior cingulate cortex, amygdala, hippocampus, cerebellum and the basal ganglia.ConclusionThe results on connectivity in MDD are very heterogeneous, partly due to different methods and study designs, but also due to the temporal dynamics of connectivity. While connectivity research is an important step toward a complex systems approach to brain functioning, future research should focus on the dynamics of functional and effective connectivity.

Cortical Midline Structures: "Self" and "Pain"

Emerging evidence indicates that cortical midline structures (CMS) (which consist of the orbitomedial prefrontal cortex (OMPFC), dorsomedial prefrontal cortex (DMPFC), anterior cingulate cortex (ACC), and precuneus/posterior cingulate cortex (pC/PCC)) have a critical role in generating a model of the self. These regions also serve as hub regions for the default mode network (DMN) or salience network (SN). Furthermore, regions of the CMS overlap with pain-related regions such as the so-called "pain matrix," suggesting that pain has unique attributes compared to other sensations like vision. Previous studies have reported that disturbances of the CMS relate to chronic pain, as well as neurological and psychiatric diseases. The considerable overlap between regions involved in pain and those involved in self-cognition may provide important insights not only into the pathology of chronic pain and cognitive aspects of pain, but also for understanding self-representation in the brain.

Repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex reduces resting-state insula activity and modulates functional connectivity of the orbitofrontal cortex in cigarette smokers

BackgroundPrevious studies reported that repetitive transcranial magnetic stimulation (rTMS) can reduce cue-elicited craving and decrease cigarette consumption in smokers. The mechanism of this effect however, remains unclear. We used resting-state functional magnetic resonance imaging (rsfMRI) to test the effect of rTMS in non-treatment seeking smokers. MethodsWe used a single blinded, sham-controlled, randomized counterbalanced crossover design where participants underwent two visits separated by at least 1 week. Participants received active rTMS over the left dorsolateral prefrontal cortex (DLPFC) during one of their visits, and sham rTMS during their other visit. They had two rsFMRI scans before and after each rTMS session. We used the same rTMS stimulation parameters as in a previous study (10Hz, 5s-on, 10s-off, 100% resting motor threshold, 3000 pulses). ResultsTen non-treatment-seeking, nicotine-dependent, cigarette smokers (6 women, an average age of 39.72 and an average cigarette per day of 17.30) finished the study. rsFMRI results demonstrate that as compared to a single session of sham rTMS, a single session of active rTMS inhibits brain activity in the right insula and thalamus in fractional amplitude of low frequency fluctuation (fALFF). For intrinsic brain connectivity comparisons, active TMS resulted in significantly decreased connectivity from the site of rTMS to the left orbitomedial prefrontal cortex. ConclusionsThis data suggests that one session of rTMS can reduce activity in the right insula and right thalamus as measured by fALFF. The data also demonstrates that rTMS can reduce rsFC between the left DLPFC and the medial orbitofrontal cortex.

Fronto-limbic disconnection in depressed patients with suicidal ideation: A resting-state functional connectivity study

BackgroundSuicidal ideation (SI) is highly prevalent and a known symptom of Major Depressive Disorder (MDD), but its underlying biological mechanisms are relatively unknown. Several studies linked suicidal ideation to dysfunctional brain circuits, specifically fronto-limbic connections. The purpose of this work was to investigate fronto-limbic disconnection in MDD patients with or without SI. MethodsMDD patients with SI (SI, n=28) or without SI (NSI, n=20), identified by the Scale for Suicide Ideation and healthy controls (HCs, n=30) underwent resting-state functional MRI scanning. The functional properties of correlations in neural activity (intrinsic functional connectivity, iFC) of the rostral anterior cingulate cortex (rACC) were analyzed among the three groups. Furthermore, correlation analyses between iFC, SI severity and depression severity were performed. ResultsWe found that the SI group exhibited decreased iFC between the rACC, the orbitomedial prefrontal cortex and the right middle temporal pole compared to HCs and NSI groups. The NSI group showed decreased iFC between the rACC and the orbitomedial prefrontal cortex compared to HCs. In the SI group, iFC strength between the right rACC and the middle temporal pole positively correlated with SI severity. ConclusionTransdiagnostic and diagnosis-specific alterations of fronto-limbic iFC were found in MDD patients with or without SI. Disrupted fronto-limbic circuits may impact decision-making and emotional processing in SI. These results provide useful information about the pathophysiological mechanisms of MDD patients with SI.

Multifaceted impairments in impulsivity and brain structural abnormalities in opioid dependence and abstinence

Chronic opioid exposure, as a treatment for a variety of disorders or as drug of misuse, is common worldwide, but behavioural and brain abnormalities remain under-investigated. Only a small percentage of patients who receive methadone maintenance treatment (MMT) for previous heroin misuse eventually achieve abstinence and studies on such patients are rare. The Cambridge Neuropsychological Test Automated Battery and T1 weighted magnetic resonance imaging (MRI) were used to study a cohort of 122 male individuals: a clinically stable opioid-dependent patient group receiving MMT (n = 48), an abstinent previously MMT maintained group (ABS) (n = 24) and healthy controls (n = 50). Stable MMT participants deliberated longer and placed higher bets earlier in the Cambridge Gambling Task (CGT) and showed impaired strategic planning compared with healthy controls. In contrast, ABS participants showed impairment in choosing the least likely outcome, delay aversion and risk adjustment on the CGT, and exhibited non-planning impulsivity compared with controls. MMT patients had widespread grey matter reductions in the orbitomedial prefrontal cortex, caudate, putamen and globus pallidus. In contrast, ABS participants showed midbrain-thalamic grey matter reductions. A higher methadone dose at the time of scanning was associated with a smaller globus pallidus in the MMT group. Our findings support an interpretation of heightened impulsivity in patients receiving MMT. Widespread structural brain abnormalities in the MMT group and reduced brain structural abnormality with abstinence suggest benefit of cessation of methadone intake. We suggest that a longitudinal study is required to determine whether abstinence improves abnormalities, or patients who achieve abstinence have reduced abnormalities before methadone cessation.

Age-related Volumetric Changes of Prefrontal Gray and White Matter from Healthy Infancy to Adulthood

Despite increasing evidence of the role of the prefrontal cortex in providing the neural substrate of higher cognitive function and neurodevelopment, little is known about neuroanatomic changes in prefrontal subregions during human development. In this prospective study, we evaluated prefrontal gray and white matter volume in healthy infants, children, adolescents, and adults. Magnetic resonance imaging was performed on 107 healthy people aged one month to 25 years. Gray and white matter volumes of the dorsolateral, dorsomedial, orbitolateral, and orbitomedial prefrontal cortex were quantified. The results indicated that both children and early adolescents had larger dorsolateral gray matter volume than infants and adults. Dorsolateral white matter volumes in children, early adolescents, and late adolescents were larger than those of infants. Dorsomedial white matter volumes of early adolescents, late adolescents, and adults were also larger than those of infants. There was no significant difference among age groups in both orbital prefrontal regions. These findings suggest that there are two important stages of structural change of the prefrontal cortex from infancy to young adulthood. First, growth spurts of both gray matter and white matter during the first 2 years of life have been shown to occur specifically in the dorsal prefrontal cortex. Second, gray matter changes have been shown to be regionally specific, with changes in the dorsal, but not orbital, prefrontal cortex peaking during late childhood or early adolescence. Thus, developmental differences within sectors of the prefrontal lobe and evidence of neural pruning and myelination may be useful in understanding the mechanisms of neurodevelopmental disorders.

Cognitive impairment in amyotrophic lateral sclerosis: the hidden challenges

Motor neurone disease (MND) or amyotrophic lateral sclerosis (ALS) is a devastating, neurological condition. It is a progressive disease that attacks the nerves in the brain and spinal cord, leading to progressive weakness and wasting of muscles. This can lead to difficulties in walking, speech, eating, drinking and breathing (MND Association, 2016). MND is a rapidly progressive disease with death usually occurring 2–5 years from onset of first symptom. Diagnosis is usually made around 12 months from first symptom, with the diagnosis typically being made around the midpoint (50% of total disease duration elapsed) of the disease pathway (Mitchell et al, 2010). Although it is progressive, the rate and nature of progression can be unpredictable, with damage to affected areas occurring in no specific order (MND Association, 2016). The incidence of MND in England, Wales and Northern Ireland is approximately 1–2 cases per 100 000 people per year, very similar to multiple sclerosis. However, due to the rapid progression of MND the prevalence is only about 4–5 per 100 000 compared to about 50 per 100 000 for MS. (MND Association, 2015). People with MND are said to have a series of losses, including the: ■Loss of movement ■Loss of speech ■Loss of ability to eat, drink and breathe. They can have many health and social care professionals involved in their care at any one time. Although often grateful for the support and advice, it can be overwhelming and patients are often confused about roles (Oliver and Webb, 2000). The management of MND is usually provided by a multidisciplinary team based in the hospital and community. There is no cure for MND, with treatment limited to one drug, Riluzole, known to extend survival by only 2–3 months, and has been recommended by the National Institute of Health and Care Excellence (NICE, 2001). The main areas of intervention, are therefore symptom management, and supportive, including interventions to improve quality of life. These may include enteral feeding (Miller et al, 2012; Stavroulakis et al, 2014) and ventilation (Baxter et al, 2013). The physical manifestations of MND/ALS are well known and widely researched. In comparison cognitive impairment in MND is less well recognised.

Subdivisions and connectional networks of the lateral prefrontal cortex in the macaque monkey

Neuroanatomical studies have long indicated that corticocortical connections are organized in networks that relate distinct sets of areas. Such networks have been emphasized by development of functional imaging methods for correlating activity across the cortex. Previously, two networks were recognized in the orbitomedial prefrontal cortex, the "orbital" and "medial" networks (OPFC and MPFC, respectively). In this study, three additional networks are proposed for the lateral prefrontal cortex: 1) a ventrolateral network (VLPFC) in and ventral to the principal sulcus; 2) a dorsal network (DPFC) in and dorsal to the principal sulcus and in the frontal pole; 3) a caudolateral network (CLPFC) in and rostral to the arcuate sulcus and the caudal principal sulcus. The connections of the first two networks are described here. Areas in each network are connected primarily with other areas in the same network, with overlaps around the principal sulcus. The VLPFC and DPFC are also connected with the OPFC and MPFC, respectively. Outside the prefrontal cortex, the VLPFC connects with specific areas related to somatic/visceral sensation and vision, in the frontoparietal operculum, insula, ventral bank/fundus of the superior temporal sulcus, inferior temporal gyrus, and inferior parietal cortex. In contrast, the DPFC connects with the rostral superior temporal gyrus, dorsal bank of the superior temporal sulcus, parahippocampal cortex, and posterior cingulate and retrosplenial cortex. Area 45a, in caudal VLPFC, is unique, having connections with all the networks. Its extrinsic connections resemble those of the DPFC. In addition, it has connections with both auditory belt/parabelt areas, and visual related areas.

Two separate, but interacting, neural systems for familiarity and novelty detection: A dual‐route mechanism

It has long been assumed that familiarity- and novelty-related processes fall on a single continuum drawing on the same cognitive and neural mechanisms. The possibility that familiarity and novelty processing involve distinct neural networks was explored in a functional magnetic resonance imaging study (fMRI), in which familiarity and novelty judgments were made in contexts emphasizing either familiarity or novelty decisions. Parametrically modulated BOLD responses to familiarity and novelty strength were isolated in two separate, nonoverlapping brain networks. The novelty system involved brain regions along the ventral visual stream, the hippocampus, and the perirhinal and parahippocampal cortices. The familiarity system, on the other hand, involved the dorsomedial thalamic nucleus, and regions within the medial prefrontal cortex and the medial and lateral parietal cortex. Convergence of the two networks, treating familiarity and novelty as a single continuum was only found in a fronto-parietal network. Finally, the orbitomedial prefrontal cortex was found to be sensitive to reported strength/confidence, irrespective of stimulus' familiarity or novelty. This pattern of results suggests a dual-route mechanism supported by the existence of two distinct but interacting functional systems for familiarity and novelty. Overall, these findings challenge current assumptions regarding the neural systems that support the processing of novel and familiar information, and have important implications for research into the neural bases of recognition memory.

EPA-1757 – Globus pallidus abnormalities in opiate dependent patients receiving methadone maintenance therapy

Introduction Preclinical studies have suggested that continuous, long-term opiate exposure may be neurotoxic. There is accumulating evidence for neural and neuropsychological abnormalities in diverse human drug addiction populations. However, the structural and behavioural correlates of human opiate dependency have been less studied than other drugs. Aims We investigated brain structure and neuropsychological functioning in opiate dependent, treatment-seeking patients receiving Methadone Maintenance Treatment, to test hypotheses of regional grey matter reductions correlating with methadone exposure and neuropsychological measures. Methods Cambridge Gambling Task (CGT) data were acquired from 47 patients receiving MMT and 51 controls. T1 weighted Magnetic Resonance Images were acquired from a representative subset of these volunteers. Results MMT patients exhibited grey matter reductions in the orbito-medial prefrontal cortex and basal ganglia. Additionally, patients exhibited significant abnormalities on CGT behavioural measures; risk adjustment, risk taking and impulsivity. Both the initial titration dose of methadone at the commencement of MMT following protocolised tolerance testing, and methadone dose at the time of scanning, correlated with grey matter reductions in the globus pallidus. Abnormal risk adjustment behaviour correlated with reductions in globus pallidus grey matter, increased risk taking with orbitofrontal grey matter reductions, and increased impulsivity with cingulate cortex reductions. Conclusions These findings support an interpretation of heightened risk taking and impulsivity in patients receiving MMT. However, the anatomically restricted correlates with indices of methadone exposure suggest that most structural brain abnormalities are not opiate linked, with the possible exception of the globus pallidus.

EPA-1759 - Brain structural abnormalities in medial temporal lobe are associated with mood and anxiety in methadone maintenance treatment

Several brain circuits are relevant in the neurobiology of addiction. Here we want to highlight symptoms related to the domains of mood, anhedonia and anxiety that may precede drug abuse and represent a specific risk factor for addiction. The mood regulation circuit that contributes to regulation of stress reactivity and the interoception circuit that contributes to awareness of drug craving and mood also participate in addiction but their involvement in the human brain has been much less investigated. Here we aim to investigate mood and anxiety in opiate dependent, treatment-seeking patients receiving Methadone Maintenance Treatment, to test hypothesis of regional grey matter reduction correlating with mood and anxiety. Cambridge Gambling Task (CGT) data were acquired from 30 patients receiving MMT and 23 controls. T1 weighted Magnetic Resonance Images were acquired from a representative subset of these volunteers. MMT patients exhibited grey matter reductions in the orbito-medial prefrontal cortex and basal ganglia. Additionally, patients exhibited significant abnormalities in the clinical rating scales BDI, Anhedonia, HAD-Anxiety, IDS and Snaith Hamilton. Increased BDI, HAD-Anxiety and IDS correlated with grey matter reductions in the hippocampus, amygdala, bed nucleus of stria terminalis and insula. Increased Snaith Hamilton correlated with grey matter reductions in periaqueductal gray, ventral tegmental area and nucleus caudate. These findings support an interpretation of a neurobiological underpinning of mood and addiction. However, the anatomically restricted correlates with mood and anxiety suggest that a rationale for adopting a mood addiction model should be further investigated.

Anterior nucleus of the thalamus

The anterior nucleus of thalamus (ANT) is a key component of the hippocampal system for episodic memory. The ANT consist of 3 subnuclei with distinct connectivity with the subicular cortex, retrosplenial cortex, and mammillary bodies. Via its connections with the anterior cingulate and orbitomedial prefrontal cortex, the ANT may also contribute to reciprocal hippocampal-prefrontal interactions involved in emotional and executive functions. As in other thalamic nuclei, neurons of the ANT have 2 different state-dependent patterns of discharge, tonic and burst-firing; some ANT neurons also contribute to propagation of the theta rhythm, which is important for mechanisms of synaptic plasticity of the hippocampal circuit. Clinical and experimental evidence indicate that damage of the ANT or its inputs from the mammillary bodies are primarily responsible for the episodic memory deficit observed in Wernicke-Korsakoff syndrome and thalamic stroke. Experimental models also indicate that the ANT may have a role in the propagation of seizure activity both in absence and in focal seizures. Because of its central connectivity and possible role in propagation of seizure activity, the ANT has become an attractive target for deep brain stimulation (DBS) for treatment of medically refractory epilepsy. The ANT is one of the nuclei preferentially affected in prion disorders, such as fatal familial insomnia, but the relationship between ANT involvement and the clinical manifestations of these disorders remains unclear. The connectivity patterns and electrophysiology of the ANT have been the subject of several reviews.(1-4.)

Just watching the game ain't enough: striatal fMRI reward responses to successes and failures in a video game during active and vicarious playing

Although the multimodal stimulation provided by modern audiovisual video games is pleasing by itself, the rewarding nature of video game playing depends critically also on the players' active engagement in the gameplay. The extent to which active engagement influences dopaminergic brain reward circuit responses remains unsettled. Here we show that striatal reward circuit responses elicited by successes (wins) and failures (losses) in a video game are stronger during active than vicarious gameplay. Eleven healthy males both played a competitive first-person tank shooter game (active playing) and watched a pre-recorded gameplay video (vicarious playing) while their hemodynamic brain activation was measured with 3-tesla functional magnetic resonance imaging (fMRI). Wins and losses were paired with symmetrical monetary rewards and punishments during active and vicarious playing so that the external reward context remained identical during both conditions. Brain activation was stronger in the orbitomedial prefrontal cortex (omPFC) during winning than losing, both during active and vicarious playing. In contrast, both wins and losses suppressed activations in the midbrain and striatum during active playing; however, the striatal suppression, particularly in the anterior putamen, was more pronounced during loss than win events. Sensorimotor confounds related to joystick movements did not account for the results. Self-ratings indicated losing to be more unpleasant during active than vicarious playing. Our findings demonstrate striatum to be selectively sensitive to self-acquired rewards, in contrast to frontal components of the reward circuit that process both self-acquired and passively received rewards. We propose that the striatal responses to repeated acquisition of rewards that are contingent on game related successes contribute to the motivational pull of video-game playing.

Neurofunctional correlates of esthetic and moral judgments

Recent neuroimaging studies indicate that there may be common ground for esthetic and moral judgments. However, because previous studies focused on either esthetic or moral judgments and did not compare the two directly, the issue remains open whether a common ground actually exists. We employed functional magnetic resonance imaging in order to study, in a within-subjects design, the potential equivalence of esthetic and moral judgments. One-line verses from poems and short moral statements were used as stimuli. Our results suggest a common basis for the two judgment categories, revealing comparable neural networks mainly the orbitomedial prefrontal cortex. However, additional activations were found in the moral judgment condition, that is, in the posterior cingulate cortex, the precuneus, and the temporoparietal junction. These regions have been related to understanding the minds of others.

Projections of the medial orbital and ventral orbital cortex in the rat

The medial orbital (MO) and ventral orbital (VO) cortices are prominent divisions of the orbitomedial prefrontal cortex. To our knowledge, no previous report in the rat has comprehensively described the projections of MO and VO. By using the anterograde tracer Phaseolus vulgaris leucoagglutinin and the retrograde tracer Fluoro-Gold, we examined the efferent projections of MO and VO in the rat. Although MO and VO projections overlap, MO distributes more widely throughout the brain, particularly to limbic structures, than does VO. The main cortical targets of MO were the orbital, ventral medial prefrontal (mPFC), agranular insular, piriform, retrosplenial, and parahippocampal cortices. The main subcortical targets of MO were the medial striatum, olfactory tubercle, claustrum, nucleus accumbens, septum, substantia innominata, lateral preoptic area, and diagonal band nuclei of the basal forebrain; central, medial, cortical, and basal nuclei of amygdala; paratenial, mediodorsal, and reuniens nuclei of the thalamus; posterior, supramammillary, and lateral nuclei of the hypothalamus; and periaqueductal gray, ventral tegmental area, substantia nigra, dorsal and median raphe, laterodorsal tegmental, and incertus nuclei of the brainstem. By comparison, VO distributes to some of these same sites, notably to the striatum, but lacks projections to parts of limbic cortex, to nucleus accumbens, and to the amygdala. VO distributes much more strongly, however, than MO to the medial (frontal) agranular, anterior cingulate, sensorimotor, posterior parietal, lateral agranular retrosplenial, and temporal association cortices. The patterns of MO projections are similar to those of the mPFC, whereas the projections of VO overlap with those of the ventrolateral orbital cortex (VLO). This suggests that MO serves functions comparable to those of the mPFC, such as goal-directed behavior, and VO performs functions similar to VLO such as directed attention. MO/VO may also serve as a link between lateral orbital and medial prefrontal cortices.