Neural activity in the human brain relating to uncertainty and arousal during anticipation

We used functional magnetic resonance neuroimaging to measure brain activity during delay between reward-related decisions and their outcomes, and the modulation of this delay activity by uncertainty and arousal. Feedback, indicating financial gain or loss, was given following a fixed delay. Anticipatory arousal was indexed by galvanic skin conductance. Delay-period activity was associated with bilateral activation in orbital and medial prefrontal, temporal, and right parietal cortices. During delay, activity in anterior cingulate and orbitofrontal cortices was modulated by outcome uncertainty, whereas anterior cingulate, dorsolateral prefrontal, and parietal cortices activity was modulated by degree of anticipatory arousal. A distinct region of anterior cingulate was commonly activated by both uncertainty and arousal. Our findings highlight distinct contributions of cognitive uncertainty and autonomic arousal to anticipatory neural activity in prefrontal cortex.     

Rôle des androgènes dans la motivation sexuelle masculine: approche par la neuroanatomie cérébrale fonctionnelle

The central nervous system plays a crucial role in all of the successive stages of sexual behaviour, particularly for the processing of external stimuli. One important step consists of the evaluation of these stimuli and the assessment of their potential reward value, which will determine the development of the sexual response. These different stages involve complex cognitive processes interacting with emotional and physiological components. Androgens, and particularly testosterone, are closely related to the regulation of sexual behaviour. Many of the various effects of testosterone on sexual behaviour have been thought to result from its effects on the central nervous system. Several studies have demonstrated that a minimum concentration of plasma testosterone is necessary to maintain a normal level of sexual desire in human males. Consequently, in normal men, acute and profound androgen deficiency induced by an experimental pharmacological treatment results in decreased sexual desire and fantasies. This reduced sexual desire is also one of the major symptoms observed in male hypogonadism. Conversely, in hypogonadal men, androgen substitution therapy results in increased sexual interest and activity. Over recent years, the development of brain functional imaging techniques (Positron Emission Tomography, functional Magnetic Resonance Imaging) has demonstrated the brain regions participating in a neural network that controls and regulates sexual arousal. We have proposed a four component neurobehavioural model, comprising cognitive (e.g. orbitofrontal cortex), motivational (e.g. anterior cingulate gyrus), emotional (e.g. somatosensory cortex, insula) and physiological (e.g. hypothalamus) processes, to describe this cerebral control of sexual motivation in human males. This network comprises activating and inhibiting structures that interact with each other. As testosterone can modulate sexual desire via its action on cerebral function, we decided to perform a brain imaging study in hypogonadal patients (both when they were untreated and when they received hormone replacement therapy), to obtain e better understanding of the specificity of these brain regions in sexual arousal processes. This study could also help describe the brain regions via which testosterone acts to modulate sexual behaviour.     

Brain Networks during Free Viewing of Complex Erotic Movie: New Insights on Psychogenic Erectile Dysfunction

Psychogenic erectile dysfunction (ED) is defined as a male sexual dysfunction characterized by a persistent or recurrent inability to attain adequate penile erection due predominantly or exclusively to psychological or interpersonal factors. Previous fMRI studies were based on the common occurrence in the male sexual behaviour represented by the sexual arousal and penile erection related to viewing of erotic movies. However, there is no experimental evidence of altered brain networks in psychogenic ED patients (EDp). Some studies showed that fMRI activity collected during non sexual movie viewing can be analyzed in a reliable manner with independent component analysis (ICA) and that the resulting brain networks are consistent with previous resting state neuroimaging studies. In the present study, we investigated the modification of the brain networks in EDp compared to healthy controls (HC), using whole-brain fMRI during free viewing of an erotic video clip. Sixteen EDp and nineteen HC were recruited after RigiScan evaluation, psychiatric, and general medical evaluations. The performed ICA showed that visual network (VN), default-mode network (DMN), fronto-parietal network (FPN) and salience network (SN) were spatially consistent across EDp and HC. However, between-group differences in functional connectivity were observed in the DMN and in the SN. In the DMN, EDp showed decreased connectivity values in the inferior parietal lobes, posterior cingulate cortex and medial prefrontal cortex, whereas in the SN decreased and increased connectivity was observed in the right insula and in the anterior cingulate cortex respectively. The decreased levels of intrinsic functional connectivity principally involved the subsystem of DMN relevant for the self relevant mental simulation that concerns remembering of past experiences, thinking to the future and conceiving the viewpoint of the other’s actions. Moreover, the between group differences in the SN nodes suggested a decreased recognition of autonomical and sexual arousal changes in EDp.     

Reward Sensitivity Modulates Brain Activity in the Prefrontal Cortex,ACC and Striatum during Task Switching

Current perspectives on cognitive control acknowledge that individual differences in motivational dispositions may modulate cognitive processes in the absence of reward contingencies. This work aimed to study the relationship between individual differences in Behavioral Activation System (BAS) sensitivity and the neural underpinnings involved in processing a switching cue in a task-switching paradigm. BAS sensitivity was hypothesized to modulate brain activity in frontal regions, ACC and the striatum. Twenty-eight healthy participants underwent fMRI while performing a switching task, which elicited activity in fronto-striatal regions during the processing of the switch cue. BAS sensitivity was negatively associated with activity in the lateral prefrontal cortex, anterior cingulate cortex and the ventral striatum. Combined with previous results, our data indicate that BAS sensitivity modulates the neurocognitive processes involved in task switching in a complex manner depending on task demands. Therefore, individual differences in motivational dispositions may influence cognitive processing in the absence of reward contingencies.     

A right hemispheric prefrontal system for cognitive time measurement

Despite a growing body of neuroimaging data, little consensus has been reached regarding the neural correlates of temporal processing in humans. This paper presents a reanalysis of two previously published neuroimaging experiments, which used two different cognitive timing tasks and examined both sub- and supra-second intervals. By processing these data in an identical manner, this reanalysis allows valid comparison and contrasting across studies. Conjunction of these studies using inclusive masking reveals shared activity in right hemispheric dorsolateral and ventrolateral prefrontal cortex and anterior insula, supporting a general-purpose system for cognitive time measurement in the right hemispheric prefrontal cortex. Consideration of the patterns of activity in each dataset with respect to the others, and taking task characteristics into account, provides insight into the possible role of dorsolateral prefrontal cortex in working memory and of posterior parietal cortex and anterior cingulate in attentional processing during cognitive time measurement tasks.     

Central nervous system involvement in the autonomic responses to psychological distress

Psychological distress can trigger acute coronary syndromes and sudden cardiac death in vulnerable patients. The primary pathophysiological mechanism that plays a role in stress-induced cardiac events involves the autonomic nervous system, particularly disproportional sympathetic activation and parasympathetic withdrawal. This article describes the relation between psychological distress and autonomic nervous system function, with a focus on subsequent adverse cardiovascular outcomes. The role of the central nervous system in these associations is addressed, and a systematic review is presented of studies examining the association between stress-induced central nervous system responses measured by neuroimaging techniques and autonomic nervous system activation. Results of the systematic review indicate that the primary brain areas involved in the autonomic component of the brain-heart association are the insula, medial prefrontal cortex, and cerebellum (based on 121 participants across three studies that fitted the inclusion criteria). Other areas involved in stress-induced autonomic modulation are the (anterior) cingulate cortex, parietal cortex, somatomotor cortex/precentral gyrus, and temporal cortex. The interaction between central and autonomic nervous system responses may have implications for further investigations of the brain-heart associations and mechanisms by which acute and chronic psychological distress increase the risk of myocardial infarction, cardiac arrhythmias, and sudden cardiac death.     

Can the Neural Basis of Repression Be Studied in the MRI Scanner? New Insights from Two Free Association Paradigms

Background

The psychodynamic theory of repression suggests that experiences which are related to internal conflicts become unconscious. Previous attempts to investigate repression experimentally were based on voluntary, intentional suppression of stimulus material. Unconscious repression of conflict-related material is arguably due to different processes, but has never been studied with neuroimaging methods.

Methods

We used functional magnetic resonance imaging (fMRI) in addition with skin conductance recordings during two free association paradigms to identify the neural mechanisms underlying forgetting of freely associated words according to repression theory.

Results

In the first experiment, free association to subsequently forgotten words was accompanied by increases in skin conductance responses (SCRs) and reaction times (RTs), indicating autonomic arousal, and by activation of the anterior cingulate cortex. These findings are consistent with the hypothesis that these associations were repressed because they elicited internal conflicts. To test this idea more directly, we conducted a second experiment in which participants freely associated to conflict-related sentences. Indeed, these associations were more likely to be forgotten than associations to not conflict-related sentences and were accompanied by increases in SCRs and RTs. Furthermore, we observed enhanced activation of the anterior cingulate cortex and deactivation of hippocampus and parahippocampal cortex during association to conflict-related sentences.

Conclusions

These two experiments demonstrate that high autonomic arousal during free association predicts subsequent memory failure, accompanied by increased activation of conflict-related and deactivation of memory-related brain regions. These results are consistent with the hypothesis that during repression, explicit memory systems are down-regulated by the anterior cingulate cortex.     

Neural Correlates of Attentional Flexibility during Approach and Avoidance Motivation

Dynamic, momentary approach or avoidance motivational states have downstream effects on eventual goal success and overall well being, but there is still uncertainty about how those states affect the proximal neurocognitive processes (e.g., attention) that mediate the longer-term effects. Attentional flexibility, or the ability to switch between different attentional foci, is one such neurocognitive process that influences outcomes in the long run. The present study examined how approach and avoidance motivational states affect the neural processes involved in attentional flexibility using fMRI with the aim of determining whether flexibility operates via different neural mechanisms under these different states. Attentional flexibility was operationalized as subjects’ ability to switch between global and local stimulus features. In addition to subjects’ motivational state, the task context was manipulated by varying the ratio of global to local trials in a block in light of recent findings about the moderating role of context on motivation-related differences in attentional flexibility. The neural processes involved in attentional flexibility differ under approach versus avoidance states. First, differences in the preparatory activity in key brain regions suggested that subjects’ preparedness to switch was influenced by motivational state (anterior insula) and the interaction between motivation and context (superior temporal gyrus, inferior parietal lobule). Additionally, we observed motivation-related differences the anterior cingulate cortex during switching. These results provide initial evidence that motivation-induced behavioral changes may arise via different mechanisms in approach versus avoidance motivational states.     

Letter to the Editor: Seasonal Pattern of Births in Patients with Optic Neuritis

Attentional processes are fundamental to good cognitive functioning of human operators. The purpose of this study was to analyze the activity of neuronal networks involved in the orienting attention and executive control processes from the perspective of diurnal variability. Twenty-three healthy male volunteers meeting magnetic resonance (MR) inclusion criteria performed the Stroop Color-Word task (block design) in the MR scanner five times/day (06:00, 10:00, 14:00, 18:00, 22:00 h). The first scanning session was scheduled 1–1.5 h after waking. Between MR sessions, subjects performed simulated driving tasks in stable environmental conditions, with controlled physical activity and diet. Significant activation was found in brain regions related to the orienting attentional system: the parietal lobe (BA40) and frontal eye-fields (FEFs). There were also activations in areas of the executive control system: the fronto-insular cortex (FIC), dorsal anterior cingulate cortex (dACC), presupplementary motor area (preSMA), supplementary motor area (SMA), basal ganglia, middle temporal (MT; BA21), and dorsolateral prefrontal cortex (DLPFC), as a part of the central executive network. Significant deactivations were observed in the rostral anterior cingulate cortex (rACC), posterior cingulate cortex (PCC), superior frontal gyrus (SF), parietal lobe (BA39), and parahippocampal that are thought to comprise the default mode network (DMN). Additionally, the activated regions included bilaterally lingual gyrus and fusiform gyrus. The insula was bilaterally deactivated. Visual attention controlled by the goal-oriented attention system and comprising top-down and bottom-up mechanisms, activated by Stroop-like task, turned out to be prone to diurnal changes. The study results show the occurrence of time-of-day–related variations in neural activity of brain regions linked to the orienting attentional system (left parietal lobe—BA40, left and right FEFs), simultaneously providing arguments for temporal stability of the executive system and default mode network. These results also seem to suggest that the involuntary, exogenous (bottom-up) mechanism of attention is more vulnerable to circadian and fatigue factors than the voluntary (top-down) mechanism, which appear to be maintained at the same functional level during the day. The above phenomena were observed at the neural level. (Author correspondence: marek@uj.edu.pl)     

Levodopa Effects on Hand and Speech Movements in Patients with Parkinson’s Disease: A fMRI Study

Levodopa (L-dopa) effects on the cardinal and axial symptoms of Parkinson’s disease (PD) differ greatly, leading to therapeutic challenges for managing the disabilities in this patient’s population. In this context, we studied the cerebral networks associated with the production of a unilateral hand movement, speech production, and a task combining both tasks in 12 individuals with PD, both off and on levodopa (L-dopa). Unilateral hand movements in the off medication state elicited brain activations in motor regions (primary motor cortex, supplementary motor area, premotor cortex, cerebellum), as well as additional areas (anterior cingulate, putamen, associative parietal areas); following L-dopa administration, the brain activation profile was globally reduced, highlighting activations in the parietal and posterior cingulate cortices. For the speech production task, brain activation patterns were similar with and without medication, including the orofacial primary motor cortex (M1), the primary somatosensory cortex and the cerebellar hemispheres bilaterally, as well as the left- premotor, anterior cingulate and supramarginal cortices. For the combined task off L-dopa, the cerebral activation profile was restricted to the right cerebellum (hand movement), reflecting the difficulty in performing two movements simultaneously in PD. Under L-dopa, the brain activation profile of the combined task involved a larger pattern, including additional fronto-parietal activations, without reaching the sum of the areas activated during the simple hand and speech tasks separately. Our results question both the role of the basal ganglia system in speech production and the modulation of task-dependent cerebral networks by dopaminergic treatment.     

Functional Anatomy of Recognition of Chinese Multi-Character Words: Convergent Evidence from Effects of Transposable Nonwords,Lexicality, and Word Frequency

This fMRI study aimed to identify the neural mechanisms underlying the recognition of Chinese multi-character words by partialling out the confounding effect of reaction time (RT). For this purpose, a special type of nonword—transposable nonword—was created by reversing the character orders of real words. These nonwords were included in a lexical decision task along with regular (non-transposable) nonwords and real words. Through conjunction analysis on the contrasts of transposable nonwords versus regular nonwords and words versus regular nonwords, the confounding effect of RT was eliminated, and the regions involved in word recognition were reliably identified. The word-frequency effect was also examined in emerged regions to further assess their functional roles in word processing. Results showed significant conjunctional effect and positive word-frequency effect in the bilateral inferior parietal lobules and posterior cingulate cortex, whereas only conjunctional effect was found in the anterior cingulate cortex. The roles of these brain regions in recognition of Chinese multi-character words were discussed.     

Neural activation in women in response to masculinized male faces: mediation by hormones and psychosexual factors

Women's preference for masculine faces varies with hormonal state, sociosexuality, and relationship status, but the underlying mechanisms are poorly understood. We hypothesized that hormones and psychosexual factors (sociosexuality, sexual inhibition/excitation) mediate the perception and evaluation of male faces thereby influencing women's preferences. We used functional magnetic resonance imaging to measure brain activity in 12 women as they evaluated pictures of male faces (half 30% masculinized, half 30% feminized). Participants were heterosexual women, age 23–28 years, who were not in a committed relationship and not using hormonal contraception. Women were tested during both the follicular and luteal phase of their menstrual cycle. We found five brain regions related to face and risk processing that responded more to the masculinized than to the feminized faces, including the superior temporal gyrus, precentral gyrus, posterior cingulate cortex, inferior parietal lobule, and anterior cingulate cortex. Increased activation in the anterior cingulate cortex, specifically, may indicate that women perceive masculinized faces to be both more risky and more attractive. We did not see any areas that were more strongly activated by feminized faces. Levels of activation were influenced by hormonal and psychosexual factors. The patterns of hormonally and psychosexually mediated neural activation observed may offer insight into the cognitive processes underlying women's partner preferences.     

Neural responses during Valsalva maneuvers in obstructive sleep apnea syndrome.

The repetitive upper airway muscle atonic episodes and cardiovascular sequelae of obstructive sleep apnea (OSA) suggest dysfunction of specific neural sites that integrate afferent airway signals with autonomic and somatic outflow. We determined neural responses to the Valsalva maneuver by using functional magnetic resonance imaging. Images were collected during a baseline and three Valsalva maneuvers in 8 drug-free OSA patients and 15 controls. Multiple cortical, midbrain, pontine, and medullary regions in both groups showed intensity changes correlated to airway pressure. In OSA subjects, the left inferior parietal cortex, superior temporal gyrus, posterior insular cortex, cerebellar cortex, fastigial nucleus, and hippocampus showed attenuated signal changes compared with controls. Enhanced responses emerged in the left lateral precentral gyrus, left anterior cingulate, and superior frontal cortex of OSA patients. The anterior cingulate, cerebellar cortex, and posterior insula exhibited altered response timing patterns between control and OSA subjects. The response patterns in OSA subjects suggest deficits in particular neural pathways that normally mediate the Valsalva maneuver and compensatory actions in other structures.     

Altered Neural Basis of the Reality Processing and Its Relation to Cognitive Insight in Schizophrenia

It has been reported that reality evaluation and recognition are impaired in patients with schizophrenia and these impairments are related to the severity of psychotic symptoms. The current study aimed to investigate the neural basis of impairments in reality evaluation and recognition and their relationships with cognitive insight in schizophrenia. During functional magnetic resonance imaging, 20 patients with schizophrenia and 20 healthy controls performed a set of reality evaluation and recognition tasks, in which subjects judged whether scenes in a series of drawings were real or unreal and whether they were familiar or novel. During reality evaluation, patients showed decreased activity in various regions including the inferior parietal lobule, retrosplenial cortex and parahippocampal gyrus, compared with controls. Particularly, parahippocampal gyrus activity was correlated with the severity of positive symptoms in patients. During recognition, patients also exhibited decreased activity in various regions, including the dorsolateral prefrontal cortex, inferior parietal lobule and posterior cingulate cortex. Particularly, inferior parietal lobule activity and posterior cingulate cortex activity were correlated with cognitive insight in patients. These findings provide evidence that neural impairments in reality evaluation and recognition are related to psychotic symptoms. Anomalous appraisal of context by dysfunctions in the context network may contribute to impairments in the reality processing in schizophrenia, and abnormal declarative memory processes may be involved in cognitive insight in patients with schizophrenia.     

Protease activated receptors 1 and 4 sensitize TRPV1 in nociceptive neurones

The basal ganglia (BG) are composed of several nuclei involved in neural processing related to the execution of motor, cognitive and emotional activities. Preclinical and clinical data have implicated a role for these structures in pain processing. Recently neuroimaging has added important information on BG activation in conditions of acute pain, chronic pain and as a result of drug effects. Our current understanding of alterations in cortical and sub-cortical regions in pain suggests that the BG are uniquely involved in thalamo-cortico-BG loops to integrate many aspects of pain. These include the integration of motor, emotional, autonomic and cognitive responses to pain.     

Pathobiology of visceral pain: molecular mechanisms and therapeutic implications V. Central nervous system processing of somatic and visceral sensory signals

Somatic and visceral sensation, including pain perception, can be studied noninvasively in humans with functional brain imaging techniques. Positron emission tomography and functional magnetic resonance imaging have identified a series of cerebral regions involved in the processing of somatic pain, including the anterior cingulate, insular, prefrontal, inferior parietal, primary and secondary somatosensory, and primary motor and premotor cortices, the thalamus, hypothalamus, brain stem, and cerebellum. Experimental evidence supports possible specific roles for individual structures in processing the various dimensions of pain, such as encoding of affect in the anterior cingulate cortex. Visceral sensation has been examined in the setting of myocardial ischemia, distension of hollow viscera, and esophageal acidification. Although knowledge regarding somatic sensation is more extensive than the information available for visceral sensation, important similarities have emerged between cerebral representations of somatic and visceral pain.     

Functional neuroanatomy of the hypnotic state

The neural mechanisms underlying hypnosis and especially the modulation of pain perception by hypnosis remain obscure. Using PET we first described the distribution of regional cerebral blood flow during the hypnotic state. Hypnosis relied on revivification of pleasant autobiographical memories and was compared to imaging autobiographical material in "normal alertness". The hypnotic state was related to the activation of a widespread set of cortical areas involving occipital, parietal, precentral, premotor, and ventrolateral prefrontal and anterior cingulate cortices. This pattern of activation shares some similarities with mental imagery, from which it mainly differs by the relative deactivation of precuneus. Second, we looked at the anti-nociceptive effects of hypnosis. Compared to the resting state, hypnosis reduced pain perception by approximately 50%. The hypnosis-induced reduction of affective and sensory responses to noxious thermal stimulation were modulated by the activity in the midcingulate cortex (area 24a'). Finally, we assessed changes in cerebral functional connectivity related to hypnosis. Compared to normal alertness (i.e., rest and mental imagery), the hypnotic state, significantly enhanced the functional modulation between midcingulate cortex and a large neural network involved in sensory, affective, cognitive and behavioral aspects of nociception. These findings show that not only pharmacological but also psychological strategies for pain control can modulate the cerebral network involved in noxious perception.     

Primate anterior cingulate cortex: where motor control, drive and cognition interface

Controversy surrounds the function of the anterior cingulate cortex. Recent discussions about its role in behavioural control have centred on three main issues: its involvement in motor control, its proposed role in cognition and its relationship with the arousal/drive state of the organism. I argue that the overlap of these three domains is key to distinguishing the anterior cingulate cortex from other frontal regions, placing it in a unique position to translate intentions to actions.