Activity in orbitofrontal neuronal ensembles reflects inhibitory control

Stopping, or inhibition, is a form of self‐control that is a core element of flexible and adaptive behavior. Its neural origins remain unclear. Some views hold that inhibition decisions reflect the aggregation of widespread and diverse pieces of information, including information arising in ostensible core reward regions (i.e., outside the canonical executive system). We recorded activity of single neurons in the orbitofrontal cortex (OFC) of macaques, a region associated with economic decisions, and whose role in inhibition is debated. Subjects performed a classic inhibition task known as the stop signal task. Ensemble decoding analyses reveal a clear firing rate pattern that distinguishes successful from failed inhibition and that begins after the stop signal and before the stop signal reaction time (SSRT). We also found a different and orthogonal ensemble pattern that distinguishes successful from failed stopping before the beginning of the trial. These signals were distinct from, and orthogonal to, value encoding, which was also observed in these neurons. The timing of the early and late signals was, respectively, consistent with the idea that neuronal activity in OFC encodes inhibition both proactively and reactively.     

Structural correlates of the orbitofrontal cortex and amygdala and personality in female adolescents

The five‐factor model consists of cognitive‐affective‐behavioral trait dimensions (neuroticism, extraversion, openness to experience, agreeableness, conscientiousness) that are central to models of psychopathology. In adults, individual differences in three of the Big Five traits, neuroticism, extraversion, and conscientiousness, have been linked to structural morphology and connectivity of the orbitofrontal cortex (OFC) and the amygdala, two brain regions critically involved in affective and regulatory processing. It is unclear whether these associations manifest in adolescence, a critical neurodevelopmental period during which many forms of psychiatric illness emerge. A total of 223 adolescent girls (ages 14–16 years) completed a multimodal neuroimaging study that utilized T1‐weighted structural MRI (e.g., cortical thickness and volume) and tractography‐based diffusion tensor imaging (64‐direction). Cortical thickness and volume were extracted from the medial orbitofrontal cortex (mOFC) and amygdala and tractography‐based fractional anisotropy was computed in the uncinate fasciculus (UF; the white matter tract connecting the OFC to the temporal lobe). We found that high neuroticism was associated with less mOFC volume (bilateral), and low conscientiousness was associated with higher white matter integrity in the UF, more amygdala volume, and less mOFC thickness (right hemisphere). Extraversion was not observed to share associations with OFC markers. These OFC‐amygdala structural correlations to personality do not match those reported in adult samples. Multimodal neuroimaging techniques can help to clarify the underpinnings of personality development between adolescence and adulthood.     

Neural Basis of Anhedonia and Amotivation in Patients with Schizophrenia: The role of Reward System

Anhedonia, the inability to feel pleasure, and amotivation, the lack of motivation, are two prominent negative symptoms of schizophrenia, which contribute to the poor social and occupational behaviors in the patients. Recently growing evidence shows that anhedonia and amotivation are tied together, but have distinct neural correlates. It is important to note that both of these symptoms may derive from deficient functioning of the reward network. A further analysis into the neuroimaging findings of schizophrenia shows that the neural correlates overlap in the reward network including the ventral striatum, anterior cingulate cortex and orbitofrontal cortex. Other neuroimaging studies have demonstrated the involvement of the default mode network in anhedonia. The identification of a specific deficit in hedonic and motivational capacity may help to elucidate the mechanisms behind social functioning deficits in schizophrenia, and may also lead to more targeted treatment of negative symptoms.     

Measuring the mind: assessing cognitive change in clinical drug trials

Genetic variation of SLC6A4, HTR1A, MAOA, COMT and BDNF has been associated with depression, variable antidepressant drug responses as well as impacts on brain regions of emotion processing that are modulated by antidepressants. Pharmacogenetic studies are using psychometric outcome measures of drug response and are hampered by small effect sizes that might be overcome by the use of intermediate endophenotypes of drug response, which are suggested by imaging studies. Such an approach will not only tighten the relationship between genes and drug response, but also yield new insights into the neurobiology of depression and individual drug responses. This article provides a comprehensive overview of pharmacogenetic, imaging genetics and drug response studies, utilizing imaging techniques within the context of antidepressive drug therapy.     

Prenatal stress alters the behavior and dendritic morphology of the medial orbitofrontal cortex in mouse offspring during lactation

Several preclinical and clinical studies have shown that prenatal stress alters neuronal dendritic development in the prefrontal cortex, together with behavioral disturbances (anxiety). Nevertheless, neither whether these alterations are present during the lactation period, nor whether such findings may reflect the onset of anxiety disorders observed in childhood and adulthood has been studied. The central aim of the present study was to determine the effects of prenatal stress on the neuronal development and behavior of mice offspring during lactation (postnatal days 14 and 21). We studied 24 CF-1 male mice, grouped as follows: (i) control P14 (n = 6), (ii) stressed P14 (n = 6), (iii) control P21 (n = 6) and (iv) stressed P21 (n = 6). On the corresponding days, animals were evaluated with the open field test and sacrificed. Their brains were then stained in Golgi-Cox solution for 30 days. The morphological analysis dealt with the study of 96 pyramidal neurons. The results showed, first, that prenatal stress resulted in a significant (i) decrease in the apical dendritic length of pyramidal neurons in the orbitofrontal cortex at postnatal day 14, (ii) increase in the apical dendritic length of pyramidal neurons in the orbitofrontal cortex at postnatal day 21, and (iii) reduction in exploratory behavior at postnatal day 14 and 21.     

Regional inactivations of primate ventral prefrontal cortex reveal two distinct mechanisms underlying negative bias in decision making

Dysregulation of the orbitofrontal and ventrolateral prefrontal cortices is implicated in anxiety and mood disorders, but the specific contributions of each region are unknown, including how they gate the impact of threat on decision making. To address this, the effects of GABAergic inactivation of these regions were studied in marmoset monkeys performing an instrumental approach–avoidance decision-making task that is sensitive to changes in anxiety. Inactivation of either region induced a negative bias away from punishment that could be ameliorated with anxiolytic treatment. However, whereas the effects of ventrolateral prefrontal cortex inactivation on punishment avoidance were seen immediately, those of orbitofrontal cortex inactivation were delayed and their expression was dependent upon an amygdala–anterior hippocampal circuit. We propose that these negative biases result from deficits in attentional control and punishment prediction, respectively, and that they provide the basis for understanding how distinct regional prefrontal dysregulation contributes to the heterogeneity of anxiety disorders with implications for cognitive-behavioral treatment strategies.Sensitivity to threat, and the appropriate interpretation of potential threat, is crucial for an organism to survive and make optimal decisions with respect to its environment. Overestimation of threat and hypersensitivity to negative emotional information are known to inappropriately impact cost–benefit decision making in patients suffering from anxiety and depression (1, 2). This hypersensitivity is thought to be due to dysregulation within the prefrontal cortex (PFC), but how the PFC contributes to aversive processing and how it gates the impact of negative emotional information on decision making are still poorly understood.There are a number of distinct brain regions within the PFC that are dysregulated in anxiety and mood disorders, including the orbitofrontal (OFC), ventrolateral prefrontal (vlPFC), and medial prefrontal (mPFC) cortices (3–5). Of these, a region within mPFC (pregenual cingulate cortex) has been implicated in regulating negative emotional valence in decision making (6), but the contribution of the other regions remains unknown. Given the lifetime prevalence and economic cost of anxiety and depression (7), understanding how these distinct prefrontal subregions modulate the impact of emotion on decision making is crucial to identify how different types of prefrontal dysregulation contribute to the heterogeneity of anxiety and mood disorders and thus guide the development of personalized treatments. Despite the uncertainty regarding the rodent correlates of these other prefrontal regions, in particular vlPFC, there have been few studies investigating the selective contribution of these other prefrontal regions to negative decision making in primates, as most primate studies focus on reward-guided decision making (8, 9; but see refs. 10–13). However, we showed previously that selective excitotoxic lesions of either anterior OFC (antOFC; area 11) or vlPFC (area 12) heighten anxiety and Pavlovian fear responses in marmoset monkeys, demonstrating that both regions contribute independently to the regulation of negative emotion (14), but their differential contribution and their involvement in modulating the impact of anxiety on decision making remains unknown. To address this, we developed an approach–avoidance conflict task suitable for marmoset monkeys and used anatomically specific intracerebral infusions and anxiolytic drug treatment to determine how temporary inactivation of these regions affected cost–benefit decision making.     

The neural basis of individual differences in mate poaching

This study tested the hypothesis that individual differences in the activity of the orbitofrontal cortex, a region implicated in value-based decision-making, are associated with the preference for a person with a partner, which could lead to mate poaching. During functional magnetic resonance imaging (fMRI), male participants were presented with facial photographs of (a) attractive females with a partner, (b) attractive females without a partner, (c) unattractive females with a partner, and (d) unattractive females without a partner. The participants were asked to rate the degree to which they desired a romantic relationship with each female using an 8-point scale. The participants rated attractive females higher than unattractive females, and this effect was associated with ventral striatum activation. The participants also indicated lower ratings for females with a partner than for females without a partner, and this effect was associated with parietal cortex activation. As predicted, the participants characterized by higher orbitofrontal activity demonstrated a greater willingness to engage in a romantic relationship with females who have a partner compared with females who do not have a partner. These results are the first to provide a possible neural explanation for why certain individuals are willing to engage in mate poaching.     

Lateral prefrontal/orbitofrontal cortex has different roles in norm compliance in gain and loss domains: a transcranial direct current stimulation study

Sanction is used by almost all known human societies to enforce fairness norm in resource distribution. Previous studies have consistently shown that the lateral prefrontal cortex (lPFC) and the adjacent orbitofrontal cortex (lOFC) play a causal role in mediating the effect of sanction threat on norm compliance. However, most of these studies were conducted in gain domain in which resources are distributed. Little is known about the mechanisms underlying norm compliance in loss domain in which individual sacrifices are needed. Here we employed a modified version of dictator game (DG) and high‐definition transcranial direct current stimulation (HD‐tDCS) to investigate to what extent lPFC/lOFC is involved in norm compliance (with and without sanction threat) in both gain‐ and loss‐sharing contexts. Participants allocated a fixed total amount of monetary gain or loss between themselves and an anonymous partner in multiple rounds of the game. A computer program randomly decided whether a given round involved sanction threat for the participants. Results showed that disruption of the right lPFC/lOFC by tDCS increased the voluntary norm compliance in the gain domain, but not in the loss domain; tDCS on lPFC/lOFC had no effect on compliance under sanction threat in either the gain or loss domain. Our findings reveal a context‐dependent nature of norm compliance and differential roles of lPFC/lOFC in norm compliance in gain and loss domains.     

The varied semiology of seizures in the context of small anterior temporal encephaloceles

Aims. Small encephaloceles of the anterior temporal pole have been increasingly recognised as an underlying epileptogenic substrate in patients with medically refractory epilepsy. The current report aims to expand on the current knowledge by emphasising that seizure semiology in such patients can vary significantly. Methods. Patients were selected from an epilepsy surgery database between 2012 and 2017. Results. Of the 143 patients who underwent epilepsy surgery, six patients had a temporal encephalocele. Four of these patients had stereo-EEG implantation. Of the four patients studied, each had a seizure semiology discordant with an ictal focus in the temporal lobe. Intracranial EEG assessment demonstrated, irrespective of this semiology, seizures originated from the anterior temporal pole. Seizures were observed to rapidly propagate to the orbitofrontal cortex, insula, temporo-occipital junction, and posterior language regions. Engagement of the mesial temporal structures could occur early or late, however, a good surgical outcome was achieved following a focused lesionectomy in either situation. Conclusion. The major finding was that seizures arising from anterior temporal encephaloceles can have an extra-temporal semiology. The varied clinical semiology and the rapid propagation to seemingly distant cortical regions could be explained by the connectivity of the anterior temporal lobe.