Less is more: Removing a modality of an expected olfactory‐visual stimulation enhances brain activation

In recent years, multisensory integration of visual and olfactory stimuli has extensively been explored resulting in the identification of responsible brain areas. As the experimental designs of previous research often include alternating presentations of unimodal and bimodal stimuli, the conditions cannot be regarded as completely independent. This could lead to effects of an expected but surprisingly missing sensory modality. In our experiment, we used a common functional magnetic resonance imaging (fMRI) study design with alternating strong unimodal and bimodal olfactory‐visual food stimuli, in addition to a slight overhang of the bimodal stimuli in an effort to examine the effects of removing a visual or olfactory congruent stimulus for older people (41–83 years). Our results suggest that the processing of olfactory and visual stimuli stays intact over a wide age‐range and that the utilization of strong stimuli does not lead to superadditive multisensory integration in accordance with the principle of inverse effectiveness. However, our results demonstrate that the removal of a stimulus modality leads to an activation of additional brain areas. For example, when the visual stimulus modality is missing, the right posterior superior temporal gyrus shows higher activation, whereas the removal of the olfactory stimulus modality leads to higher activation in the amygdala/hippocampus and the postcentral gyrus. These brain areas are related to attention, memory, and the search of the missing stimulus. Consequently, careful attention must be paid to the design of a valid, multimodal sensory experiment while also controlling for cognitive expectancy effects that might confound multimodal results.     

Perceptual plasticity is mediated by connectivity changes of the medial thalamic nucleus

It is well known that the threshold for somatosensory perception may adapt to different inputs. Recent studies suggest the presence of a modulating effect of somatosensory inputs on the spinal dorsal horn. However, the effects of somatosensory inputs on cerebral processing and, in particular, on the functional and effective connectivity of the somatosensory brain network, are poorly understood. In this study, we investigated the longitudinal impact of somatosensory stimuli on the resting‐state functional connectivity and effective connectivity of the somatosensory brain network. We performed resting‐state functional magnetic resonance imaging (fMRI) in 12 healthy subjects before and after unilateral electrical median nerve stimulation. We combined this analysis with a psychophysiological examination of changes of the perception threshold. We found that the unilateral median nerve stimulation increased the perception thresholds bilaterally and increased the resting‐state functional and effective connectivity between most cortical areas of the somatosensory network. The major finding, however, was a decreased resting‐state functional connectivity between both secondary somatosensory cortices and the bilateral medial nuclear complex of the thalamus. This decreased connectivity was correlated with increased perception thresholds. These findings emphasize the importance of the medial thalamic nucleus for the perceptual awareness of somatosensory stimuli. Hum Brain Mapp 34:2343–2352, 2013. © 2012 Wiley Periodicals, Inc.     

Goal-directed behavior under emotional distraction is preserved by enhanced task-specific activation

Despite the distracting effects of emotional stimuli on concurrent task performance, humans are able to uphold goal-directed behavior. Here, we investigated the hypothesis that this effect is due to the enhanced recruitment of task-specific neural resources. In a two-step functional magnetic resonance imaging study, we first localized those areas involved in mental arithmetics by contrasting arithmetic problems with a number detection task. The resulting activation maps were then used as masks in a second experiment that compared the effects of neutral and emotional distracter images on mental arithmetics. We found increased response times in the emotional distracter condition, accompanied by enhanced activation in task-specific areas, including superior parietal cortex, dorsolateral and dorsomedial prefrontal cortex. This activation increase correlated with larger behavioral impairment through emotional distraction. Similar error rates in both conditions indicate that cognitive task performance is preserved through enhanced recruitment of task-specific neural resources when emotional distracter stimuli are present.     

Occipitotemporal activation evoked by the perception of human bodies is modulated by the presence or absence of the face

We investigated the degree to which activation in regions of the brain known to participate in social perception is influenced by the presence or absence of the face and other body parts. Subjects continuously viewed a static image of a lecture hall in which actors appeared briefly in various poses. There were three conditions: Body-Face, in which the actor appeared with limbs, torso, and face clearly visible; Body-Only, in which the actor appeared with his or her face occluded by a book; and Face-Only, in which the actor appeared behind a podium with only face and shoulders visible. Using event-related functional MRI, we obtained strong activation in those regions previously identified as important for face and body perception. These included portions of the fusiform (FFG) and lingual gyri within ventral occipitotemporal cortex (VOTC), and portions of the middle occipital gyrus (corresponding to the previously defined extrastriate body area, or EBA) and posterior superior temporal sulcus (pSTS) within lateral occipitotemporal cortex (LOTC). Activation of the EBA was strongest for the Body-Only condition; indeed, exposing the face decreased EBA activation evoked by the body. In marked contrast, activation in the pSTS was largest when the face was visible, regardless of whether the body was also visible. Activity within the lateral lingual gyrus and adjacent medial FFG was strongest for the Body-Only condition, while activation in the lateral FFG was greatest when both the face and body were visible. These results provide new information regarding the importance of a visible face in both the relative activation and deactivation of brain structures engaged in social perception.     

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.     

Umami: a delicious flavor formed by convergence of taste and olfactory pathways in the human brain

Umami taste is produced by glutamate acting on a fifth taste system. However, glutamate presented alone as a taste stimulus is not highly pleasant, and does not act synergistically with other tastes (sweet, salt, bitter and sour). We show here that when glutamate is given in combination with a consonant, savory, odour (vegetable), the resulting flavor can be much more pleasant. Moreover, we showed using functional brain imaging with fMRI that the glutamate taste and savory odour combination produced much greater activation of the medial orbitofrontal cortex and pregenual cingulate cortex than the sum of the activations by the taste and olfactory components presented separately. Supralinear effects were much less (and significantly less) evident for sodium chloride and vegetable odour. Further, activations in these brain regions were correlated with the pleasantness and fullness of the flavor, and with the consonance of the taste and olfactory components. Supralinear effects of glutamate taste and savory odour were not found in the insular primary taste cortex. We thus propose that glutamate acts by the nonlinear effects it can produce when combined with a consonant odour in multimodal cortical taste-olfactory convergence regions. We propose the concept that umami can be thought of as a rich and delicious flavor that is produced by a combination of glutamate taste and a consonant savory odour. Glutamate is thus a flavor enhancer because of the way that it can combine supralinearly with consonant odours in cortical areas where the taste and olfactory pathways converge far beyond the receptors.     

Overlapping patterns of brain activation to food and cocaine cues in cocaine abusers

Cocaine, through its activation of dopamine (DA) signaling, usurps pathways that process natural rewards. However, the extent to which there is overlap between the networks that process natural and drug rewards and whether DA signaling associated with cocaine abuse influences these networks have not been investigated in humans. We measured brain activation responses to food and cocaine cues with fMRI, and D2/D3 receptors in the striatum with [¹¹C]raclopride and Positron emission tomography in 20 active cocaine abusers. Compared to neutral cues, food and cocaine cues increasingly engaged cerebellum, orbitofrontal, inferior frontal, and premotor cortices and insula and disengaged cuneus and default mode network (DMN). These fMRI signals were proportional to striatal D2/D3 receptors. Surprisingly cocaine and food cues also deactivated ventral striatum and hypothalamus. Compared to food cues, cocaine cues produced lower activation in insula and postcentral gyrus, and less deactivation in hypothalamus and DMN regions. Activation in cortical regions and cerebellum increased in proportion to the valence of the cues, and activation to food cues in somatosensory and orbitofrontal cortices also increased in proportion to body mass. Longer exposure to cocaine was associated with lower activation to both cues in occipital cortex and cerebellum, which could reflect the decreases in D2/D3 receptors associated with chronicity. These findings show that cocaine cues activate similar, though not identical, pathways to those activated by food cues and that striatal D2/D3 receptors modulate these responses, suggesting that chronic cocaine exposure might influence brain sensitivity not just to drugs but also to food cues. Hum Brain Mapp, 36:120–136, 2015. © 2014 Wiley Periodicals, Inc .     

BOLD fMRI deactivation of limbic and temporal brain structures and mood enhancing effect by transcutaneous vagus nerve stimulation

Summary Direct vagus nerve stimulation (VNS) has proved to be an effective treatment for seizure disorder and major depression. However, since this invasive technique implies surgery, with its side-effects and relatively high financial costs, a non-invasive method to stimulate vagal afferences would be a great step forward. We studied effects of non-invasive electrical stimulation of the nerves in the left outer auditory canal in healthy subjects (n = 22), aiming to activate vagal afferences transcutaneously (t-VNS). Short-term changes in brain activation and subjective well-being induced by t-VNS were investigated by functional magnetic resonance imaging (fMRI) and psychometric assessment using the Adjective Mood Scale (AMS), a self-rating scale for current subjective feeling. Stimulation of the ear lobe served as a sham control. fMRI showed that robust t-VNS induced BOLD-signal decreases in limbic brain areas, including the amygdala, hippocampus, parahippocampal gyrus and the middle and superior temporal gyrus. Increased activation was seen in the insula, precentral gyrus and the thalamus. Psychometric assessment revealed significant improvement of well-being after t-VNS. Ear lobe stimulation as a sham control intervention did not show similar effects in either fMRI or psychometric assessment. No significant effects on heart rate, blood pressure or peripheral microcirculation could be detected during the stimulation procedure. Conclusions. Our study shows the feasibility and beneficial effects of transcutaneous nerve stimulation in the left auditory canal of healthy subjects. Brain activation patterns clearly share features with changes observed during invasive vagus nerve stimulation.     

Individual sensitivity to pain expectancy is related to differential activation of the hippocampus and amygdala

Anxiety arising during pain expectancy can modulate the subjective experience of pain. However, individuals differ in their sensitivity to pain expectancy. The amygdale and hippocampus were proposed to mediate the behavioral response to aversive stimuli. However, their differential role in mediating anxiety‐related individual differences is not clear. Using fMRI, we investigated brain activity during expectancy to cued or uncued thermal pain applied to the wrist. Following each stimulation participants rated the intensity of the painful experience. Activations in the amygdala and hippocampus were examined with respect to individual differences in harm avoidance (HA) personality trait, and individual sensitivity to expectancy, (i.e. response to cued vs. uncued painful stimuli). Only half of the subjects reported on cued pain as being more painful than uncued pain. In addition, we found a different activation profile for the amygdala and hippocampus during pain expectancy and experience. The amygdala was more active during expectancy and this activity was correlated with HA scores. The hippocampal activity was equally increased during both pain expectancy and experience, and correlated with the individual's sensitivity to expectancy. Our findings suggest that the amygdala supports an innate tendency to approach or avoid pain as reflected in HA trait, whereas the hippocampus mediates the effect of context possibly via appraisal of the stimulus value. Hum Brain Mapp, 2010. © 2009 Wiley‐Liss, Inc.     

A bias‐free two‐alternative forced choice procedure to examine intersensory illusions applied to the ventriloquist effect by flashes and averted eye‐gazes

We compared with a new psychophysical method whether flashes and averted eye‐gazes of a cartoon face induce a ventriloquist illusion (an illusory shift of the apparent location of a sound by a visual distracter). With standard psychophysical procedures that measure a direct ventriloquist effect and a ventriloquist aftereffect, we found in human subjects that both types of stimuli induced an illusory shift of sound location. These traditional methods, though, are probably contaminated by response strategies. We therefore developed a new two‐alternative forced choice procedure that allows measuring the strength of an intersensory illusion in a bias‐free way. With this new procedure we found that only flashes, but not averted eye‐gazes, induced an illusory shift in sound location. This difference between flashes and eye‐gazes was validated in an EEG study in which again only flashes illusorily shifted the apparent location of a sound thereby evoking a mismatch negativity response. These results are important because they highlight that commonly used measures of multisensory illusions are contaminated while there is an easy yet stringent way to measure the strength of an illusion in a bias‐free way.     

Decision making by methamphetamine-dependent subjects is associated with error-rate-independent decrease in prefrontal and parietal activation.

BACKGROUND: One important aspect in decision making is how success or failure influences the selection of a response. In a previous investigation, methamphetamine-dependent subjects (MD) selected win-stay/lose-shift consistent responses than normal comparison subjects (NC), which may imply that MD are more influenced by success. This study examined whether the degree of success and the degree of predictability differentially affected MD's decision making. METHODS: Using functional magnetic resonance imaging, 14 MD were compared with 14 NC while performing the two-choice prediction task at three success rates and the two-choice response task. RESULTS: The increase in win-stay/lose-shift consistent responses by MD relative to NC was independent of success rate. Irrespective of success, MD showed less task-related activation in orbitofrontal cortex (Brodmann's area [BA] 10), dorsolateral prefrontal cortex (BA 9), anterior cingulate (BA 32), and parietal cortex (BA 7). Whereas NC showed success-related patterns of neural activation in the orbitofrontal, dorsolateral prefrontal, and parietal cortex, MD showed activation that was highest when the outcome was most unpredictable. CONCLUSIONS: Our results are consistent with the hypothesis of a more rigid stimulus-response relationship during MD's decision making, which may be due to a shift from processing "success" toward processing the degree of stimulus "predictability."     

Disruptions to human speed perception induced by motion adaptation and transcranial magnetic stimulation

To investigate the underlying nature of the effects of transcranial magnetic stimulation (TMS) on speed perception, we applied repetitive TMS (rTMS) to human V5/MT+ following adaptation to either fast‐ (20 deg/s) or slow (4 deg/s)‐moving grating stimuli. The adapting stimuli induced changes in the perceived speed of a standard reference stimulus moving at 10 deg/s. In the absence of rTMS, adaptation to the slower stimulus led to an increase in perceived speed of the reference, whilst adaptation to the faster stimulus produced a reduction in perceived speed. These induced changes in speed perception can be modelled by a ratio‐taking operation of the outputs of two temporally tuned mechanisms that decay exponentially over time. When rTMS was applied to V5/MT+ following adaptation, the perceived speed of the reference stimulus was reduced, irrespective of whether adaptation had been to the faster‐ or slower‐moving stimulus. The fact that rTMS after adaptation always reduces perceived speed, independent of which temporal mechanism has undergone adaptation, suggests that rTMS does not selectively facilitate activity of adapted neurons but instead leads to suppression of neural function. The results highlight the fact that potentially different effects are generated by TMS on adapted neuronal populations depending upon whether or not they are responding to visual stimuli.     

Hippocampal activation during a cognitive task is associated with subsequent neuroendocrine and cognitive responses to psychological stress

Increased activation of the hypothalamus pituitary adrenal (HPA) axis, marked by increased secretion of cortisol, is a biological marker of psychological stress. It is well established that the hippocampus plays an important role in the regulation of HPA axis activity. The relationship between cortisol (stress‐related elevation or exogenous administration) and the hippocampal‐related cognitive function is often examined. However, few human studies to date have examined the effect of stress on hippocampal activity and the interactions between stress‐induced activation of the HPA axis and hippocampal function during different phases of cognitive function. On the basis of our previous work, we hypothesized that group differences in stress‐sensitivity relate to differences in hippocampal‐related stress‐integration. To test this hypothesis, we conducted a functional MRI study using tasks known to involve the hippocampal formation: novel‐picture encoding, psychological stress, and paired‐picture recognition. On the basis of their cortisol responses to stress, we divided subjects into stress‐responders (increase in cortisol, n = 9) and nonresponders (decrease in cortisol, n = 10). Responders showed higher hippocampal deactivation during the stress task and lower recognition scores due to a larger number of misses. Intriguingly, stress‐responders showed significant differences in hippocampal activation already prior to stress, with higher levels of hippocampal activity during the picture encoding. Although effects of both cortisol and hippocampal activation on recognition were present in responders, similar effects were absent in the nonresponder group. Our results indicate that hippocampus plays an important role in adaptive behavioral responses. We hypothesize that states of hippocampal activation prior to stress might reflect states of vigilance or anxiety, which might be important for determining interindividual differences in subsequent stress response and cognitive performance. © 2009 Wiley‐Liss, Inc.     

Major depressive disorder is characterized by greater reward network activation to monetary than pleasant image rewards

Anhedonia, the loss of interest or pleasure in normally rewarding activities, is a hallmark feature of unipolar Major Depressive Disorder (MDD). A growing body of literature has identified frontostriatal dysfunction during reward anticipation and outcomes in MDD. However, no study to date has directly compared responses to different types of rewards such as pleasant images and monetary rewards in MDD. To investigate the neural responses to monetary and pleasant image rewards in MDD, a modified Monetary Incentive Delay task was used during functional magnetic resonance imaging to assess neural responses during anticipation and receipt of monetary and pleasant image rewards. Participants included nine adults with MDD and 13 affectively healthy controls. The MDD group showed lower activation than controls when anticipating monetary rewards in right orbitofrontal cortex and subcallosal cortex, and when anticipating pleasant image rewards in paracingulate and supplementary motor cortex. The MDD group had relatively greater activation in right putamen when anticipating monetary versus pleasant image rewards, relative to the control group. Results suggest reduced reward network activation in MDD when anticipating rewards, as well as relatively greater hypoactivation to pleasant image than monetary rewards.     

The activity of neurones in the lateral hypothalamus and zona incerta of the sheep responding to the sight or approach of food is modified by learning and satiety and reflects food preference

Single unit recordings were made from neurones in the lateral hypothalamus and zona incerta of conscious sheep during the static visual presentation of food or visible approach of food towards the animal's mouth. The ability of this population of neurones to modulate their activity as a result of learning and satiety was investigated together with the extent to which their responsiveness reflected individual food preference. These neurones did not respond to either the sight or visible approach of a nonsense object or a food which they would not eat. Further, when the sight or approach of food which the animal desired to eat was not paired with ingestion the neurones rapidly extinguished their response. The magnitude of the neuronal response and the number of trials to extinction was dependent upon the animal's preference for a particular food: the most preferred food evoking the greatest response and being the most resistant to extinction. Following extinction the neuronal response to the sight or approach of food could be re-established after one or two trials with food reinforcement. If the sheep was repeatedly given the same food to eat the magnitude of the neuronal response and the number of trials to extinction gradually declined until no response occured when the animal refused to eat. These cells could also be induced to respond differentially to the approach of non-food objects dependent upon whether they were associated with a food reward or not. Thus a response could be evoked to the sight or approach of a black bottle if it was associated with a food reward but not to a yellow bottle unassociated with feeding. Acquired neuronal responses to novel foods could also be demonstrated.     

Neuronal activation in female budgerigars is localized and related to male song complexity

Females of several songbird species have been shown to respond preferentially to a more complex song. The male budgerigar (Melopsittacus undulatus) sings complex songs consisting of discrete components, known as syllables. We exposed female budgerigars to either standard male song, complex song, or simple song, the iteration of only one syllable (either frequency-modulated or unmodulated). Using immunocytochemistry, we analysed the expression of the protein product of the immediate early gene ZENK in a number of forebrain regions. The level of Zenk protein expression caused by song stimuli varied among each of the brain regions. Expression was highest in the caudomedial neostriatum (NCM), lower in the caudomedial hyperstriatum ventrale (CMHV), and lowest in the hippocampus. There was a significant effect of song complexity on the number of Zenk-immunoreactive cells in the NCM, but not in the hippocampus. Zenk protein expression correlated significantly and positively with the number of different syllables to which the females were exposed in the NCM and to a lesser extent in the CMHV, but not in the hippocampus. For the NCM this correlation was also significant within the group exposed to natural song. These results suggest that the NCM is involved in the perception of song complexity in female budgerigars.     

The posterior superior temporal sulcus is sensitive to the outcome of human and non-human goal-directed actions

Prior studies have demonstrated that the posterior superior temporal sulcus (pSTS) is involved in analyzing the intentions underlying actions and is sensitive to the context within which actions occur. However, it is debated whether the pSTS is actually sensitive to goals underlying actions, or whether previous studies can be interpreted to suggest that the pSTS is instead involved in the allocation of visual attention towards unexpected events. In addition, little is known about whether the pSTS is specialized for reasoning about the actions of social agents or whether the pSTS is sensitive to the actions of both animate and inanimate entities. Here, using functional magnetic resonance imaging, we investigated activation in response to passive viewing of successful and unsuccessful animate and inanimate goal-directed actions. Activation in the right pSTS was stronger in response to failed actions compared to successful actions, suggesting that the pSTS plays a role in encoding the goals underlying actions. Activation in the pSTS did not differentiate between animate and inanimate actions, suggesting that the pSTS is sensitive to the goal-directed actions of both animate and inanimate entities.     

Pedophilia is linked to reduced activation in hypothalamus and lateral prefrontal cortex during visual erotic stimulation.

BACKGROUND: Although pedophilia is of high public concern, little is known about underlying neural mechanisms. Although pedophilic patients are sexually attracted to prepubescent children, they show no sexual interest toward adults. This study aimed to investigate the neural correlates of deficits of sexual and emotional arousal in pedophiles. METHODS: Thirteen pedophilic patients and 14 healthy control subjects were tested for differential neural activity during visual stimulation with emotional and erotic pictures with functional magnetic resonance imaging. RESULTS: Regions showing differential activations during the erotic condition comprised the hypothalamus, the periaqueductal gray, and dorsolateral prefrontal cortex, the latter correlating with a clinical measure. Alterations of emotional processing concerned the amygdala-hippocampus and dorsomedial prefrontal cortex. CONCLUSIONS: Hypothesized regions relevant for processing of erotic stimuli in healthy individuals showed reduced activations during visual erotic stimulation in pedophilic patients. This suggests an impaired recruitment of key structures that might contribute to an altered sexual interest of these patients toward adults.     

Human attachment security is mediated by the amygdala: evidence from combined fMRI and psychophysiological measures

The neural basis of human attachment security remains unexamined. Using event-related functional magnetic resonance imaging (fMRI) and simultaneous recordings of skin conductance levels, we measured neural and autonomic responses in healthy adult individuals during a semantic conceptual priming task measuring human attachment security "by proxy". Performance during a stress but not a neutral prime condition was associated with response in bilateral amygdalae. Furthermore, levels of activity within bilateral amygdalae were highly positively correlated with attachment insecurity and autonomic response during the stress prime condition. We thereby demonstrate a key role of the amygdala in mediating autonomic activity associated with human attachment insecurity.     

Association between reward‐related activation in the ventral striatum and trait reward sensitivity is moderated by dopamine transporter genotype

The impact of individual differences on human reward processing has been a focus of research in recent years, particularly, as they are associated with a variety of neuropsychiatric diseases including addiction and attention‐deficit/hyperactivity disorder. Studies exploring the neural basis of individual differences in reward sensitivity have consistently implicated the ventral striatum (VS) as a core component of the human reward system. However, the mechanisms of dopaminergic neurotransmission underlying ventral striatal activation as well as trait reward sensitivity remain speculative. We addressed this issue by investigating the triadic interplay between VS reactivity during reward anticipation using functional magnetic resonance imaging, trait reward sensitivity, and dopamine (DA) transporter genotype (40‐bp 3′VNTR of DAT, SLC6A3) affecting synaptic DA neurotransmission. Our results show that DAT variation moderates the association between VS‐reactivity and trait reward sensitivity. Specifically, homozygote carriers of the DAT 10‐repeat allele exhibit a strong positive correlation between reward sensitivity and reward‐related VS activity whereas this relationship is absent in the DAT 9‐repeat allele carriers. We discuss the possibility that this moderation of VS‐trait relation might arise from DAT‐dependent differences in DA availability affecting synaptic plasticity within the VS. Generally, studying the impact of dopaminergic gene variations on the relation between reward‐related brain activity and trait reward sensitivity might facilitate the investigation of complex mechanisms underlying disorders linked to dysregulation of DA neurotransmission. Hum Brain Mapp, 2010. © 2010 Wiley‐Liss, Inc.