Risk profiles for heavy drinking in adolescence: differential effects of gender.

Abnormalities across different domains of neuropsychological functioning may constitute a risk factor for heavy drinking during adolescence and for developing alcohol use disorders later in life. However, the exact nature of such multi-domain risk profiles is unclear, and it is further unclear whether these risk profiles differ between genders. We combined longitudinal and cross-sectional analyses on the large IMAGEN sample (N ≈ 1000) to predict heavy drinking at age 19 from gray matter volume as well as from psychosocial data at age 14 and 19-for males and females separately. Heavy drinking was associated with reduced gray matter volume in 19-year-olds' bilateral ACC, MPFC, thalamus, middle, medial and superior OFC as well as left amygdala and anterior insula and right inferior OFC. Notably, this lower gray matter volume associated with heavy drinking was stronger in females than in males. In both genders, we observed that impulsivity and facets of novelty seeking at the age of 14 and 19, as well as hopelessness at the age of 14, are risk factors for heavy drinking at the age of 19. Stressful life events with internal (but not external) locus of control were associated with heavy drinking only at age 19. Personality and stress assessment in adolescents may help to better target counseling and prevention programs. This might reduce heavy drinking in adolescents and hence reduce the risk of early brain atrophy, especially in females. In turn, this could additionally reduce the risk of developing alcohol use disorders later in adulthood.

Activation in the angular gyrus and in the pSTS is modulated by face primes during voice recognition.

The aim of the present study was to better understand the interaction of face and voice processing when identifying people. In a S1-S2 crossmodal priming fMRI experiment, the target (S2) was a disyllabic voice stimulus, whereas the modality of the prime (S1) was manipulated blockwise and consisted of the silent video of a speaking face in the crossmodal condition or of a voice stimulus in the unimodal condition. Primes and targets were from the same speaker (person-congruent) or from two different speakers (person-incongruent). Participants had to classify the S2 as either an old or a young person. Response times were shorter after a congruent than after an incongruent face prime. The right posterior superior temporal sulcus (pSTS) and the right angular gyrus showed a significant person identity effect (person-incongruent > person-congruent) in the crossmodal condition but not in the unimodal condition. In the unimodal condition, a person identity effect was observed in the bilateral inferior frontal gyrus. Our data suggest that both the priming with a voice and with a face result in a preactivated voice representation of the respective person, which eventually facilitates (person-congruent trials) or hampers (person-incongruent trials) the processing of the identity of a subsequent voice. This process involves activation in the right pSTS and in the right angular gyrus for voices primed by faces, but not for voices primed by voices. Hum Brain Mapp 38:2553-2565, 2017. © 2017 Wiley Periodicals, Inc.

Crossmodal plasticity in the fusiform gyrus of late blind individuals during voice recognition.

Blind individuals are trained in identifying other people through voices. In congenitally blind adults the anterior fusiform gyrus has been shown to be active during voice recognition. Such crossmodal changes have been associated with a superiority of blind adults in voice perception. The key question of the present functional magnetic resonance imaging (fMRI) study was whether visual deprivation that occurs in adulthood is followed by similar adaptive changes of the voice identification system. Late blind individuals and matched sighted participants were tested in a priming paradigm, in which two voice stimuli were subsequently presented. The prime (S1) and the target (S2) were either from the same speaker (person-congruent voices) or from two different speakers (person-incongruent voices). Participants had to classify the S2 as either coming from an old or a young person. Only in late blind but not in matched sighted controls, the activation in the anterior fusiform gyrus was modulated by voice identity: late blind volunteers showed an increase of the BOLD signal in response to person-incongruent compared with person-congruent trials. These results suggest that the fusiform gyrus adapts to input of a new modality even in the mature brain and thus demonstrate an adult type of crossmodal plasticity.

Neurofeedback training of gamma band oscillations improves perceptual processing.

In this study, a noninvasive electroencephalography-based neurofeedback method is applied to train volunteers to deliberately increase gamma band oscillations (40 Hz) in the visual cortex. Gamma band oscillations in the visual cortex play a functional role in perceptual processing. In a previous study, we were able to demonstrate that gamma band oscillations prior to stimulus presentation have a significant influence on perceptual processing of visual stimuli. In the present study, we aimed to investigate longer lasting effects of gamma band neurofeedback training on perceptual processing. For this purpose, a feedback group was trained to modulate oscillations in the gamma band, while a control group participated in a task with an identical design setting but without gamma band feedback. Before and after training, both groups participated in a perceptual object detection task and a spatial attention task. Our results clearly revealed that only the feedback group but not the control group exhibited a visual processing advantage and an increase in oscillatory gamma band activity in the pre-stimulus period of the processing of the visual object stimuli after the neurofeedback training. Results of the spatial attention task showed no difference between the groups, which underlines the specific role of gamma band oscillations for perceptual processing. In summary, our results show that modulation of gamma band activity selectively affects perceptual processing and therefore supports the relevant role of gamma band activity for this specific process. Furthermore, our results demonstrate the eligibility of gamma band oscillations as a valuable tool for neurofeedback applications.

Investigating the effect of respiratory bodily threat on the processing of emotional pictures.

It has been demonstrated that emotions can substantially impact the perception and neural processing of breathlessness, but little is known about the reverse interaction. Here, we examined the impact of breathlessness on emotional picture processing. The continuous EEG was recorded while volunteers viewed positive/neutral/negative emotional pictures under conditions of resistive-load-induced breathlessness, auditory noise, and an unloaded baseline. Breathlessness attenuated P1 and early posterior negativity (EPN) ERP amplitudes, irrespective of picture valence. Moreover, as expected, larger amplitudes for positive and negative pictures relative to neutral pictures were found for EPN and the late positive potential (LPP) ERPs, which were not affected by breathlessness. The results suggest that breathlessness impacts on the early attention-related neural processing of picture stimuli without influencing the later cognitive processing of emotional contents.

Brain systems mediating voice identity processing in blind humans.

Blind people rely more on vocal cues when they recognize a person's identity than sighted people. Indeed, a number of studies have reported better voice recognition skills in blind than in sighted adults. The present functional magnetic resonance imaging study investigated changes in the functional organization of neural systems involved in voice identity processing following congenital blindness. A group of congenitally blind individuals and matched sighted control participants were tested in a priming paradigm, in which two voice stimuli (S1, S2) were subsequently presented. The prime (S1) and the target (S2) were either from the same speaker (person-congruent voices) or from two different speakers (person-incongruent voices). Participants had to classify the S2 as either a old or a young person. Person-incongruent voices (S2) compared with person-congruent voices elicited an increased activation in the right anterior fusiform gyrus in congenitally blind individuals but not in matched sighted control participants. In contrast, only matched sighted controls showed a higher activation in response to person-incongruent compared with person-congruent voices (S2) in the right posterior superior temporal sulcus. These results provide evidence for crossmodal plastic changes of the person identification system in the brain after visual deprivation.

Neural evidence for adaptive strategy selection in value-based decision-making.

In everyday life, humans often encounter complex environments in which multiple sources of information can influence their decisions. We propose that in such situations, people select and apply different strategies representing different cognitive models of the decision problem. Learning advances by evaluating the success of using a strategy and eventually by switching between strategies. To test our strategy selection model, we investigated how humans solve a dynamic learning task with complex auditory and visual information, and assessed the underlying neural mechanisms with functional magnetic resonance imaging. Using the model, we were able to capture participants' choices and to successfully attribute expected values and reward prediction errors to activations in the dopaminoceptive system (e.g., ventral striatum [VS]) as well as decision conflict to signals in the anterior cingulate cortex. The model outperformed an alternative approach that did not update decision strategies, but the relevance of information itself. Activation of sensory areas depended on whether the selected strategy made use of the respective source of information. Selection of a strategy also determined how value-related information influenced effective connectivity between sensory systems and the VS. Our results suggest that humans can structure their search for and use of relevant information by adaptively selecting between decision strategies.

Expectation requires treatment to boost pain relief: an fMRI study.

We investigated the effect of a possible interaction between topical analgesic treatment and treatment expectation on pain at the behavioral and neuronal level by combining topical lidocaine/prilocaine treatment with an expectancy manipulation in a 2 by 2 within-subject design (open treatment, hidden treatment, placebo, control). Thirty-two healthy subjects received heat pain stimuli on capsaicin-pretreated skin and rated their experienced pain during functional magnetic resonance imaging. This allowed us to separate drug- and expectancy-related effects at the behavioral and neuronal levels and to test whether they interact during the processing of painful stimuli. Pain ratings were reduced during active treatment and were associated with reduced activity in the anterior insular cortex. Pain ratings were lower in open treatment compared with hidden treatment and were related to reduced activity in the anterior insular cortex, the anterior cingulate cortex, the secondary somatosensory cortex, and the thalamus. Testing for an interaction revealed that the expectation effect was significantly larger in the active treatment conditions compared with the no-treatment conditions and was associated with signal changes in the anterior insular cortex, the anterior cingulate cortex, and the ventral striatum. In conclusion, this study shows that even in the case of a topical analgesic, expectation interacts with treatment at the level of pain ratings and neuronal responses in placebo-related brain regions. Our results are highly relevant in the clinical context as they show (i) that expectation can boost treatment and (ii) that expectation and treatment are not necessarily additive as assumed in placebo-controlled clinical trials.

Facilitation of pain in the human spinal cord by nocebo treatment.

Nocebo hyperalgesia is an increase in subjective pain perception after a patient or subject underwent an inert treatment without any active ingredient. For example, verbal suggestion of increased pain can enhance both pain experience and responses in pain-related cortical brain areas. However, changes in cortical pain responses may be secondary to earlier amplification of incoming pain signals within the spinal cord. To test for a potential early enhancement of pain signals in the dorsal horn of the spinal cord, we combined a nocebo heat pain paradigm with spinal functional magnetic resonance imaging in healthy volunteers. We found that local application of an inert nocebo cream on the forearm increased pain ratings compared with a control cream, and also reduced pain thresholds on the nocebo-treated skin patch. On the neurobiological level, pain stimulation induced a strong activation in the spinal cord at the level of the stimulated dermatomes C5/C6. Comparing pain stimulation under nocebo to a control pain stimulation of the same physical intensity revealed enhanced pain-related activity in the ipsilateral dorsal horn of the spinal cord. Importantly, the activation of the main effect of pain and the nocebo effect spatially overlapped. The current study thus provides direct evidence for a pain-facilitating mechanism in the human spinal cord before cortical processing, which can be activated by cognitive manipulations such as nocebo treatments.

A target sample of adolescents and reward processing: same neural and behavioral correlates engaged in common paradigms?

Adolescence is a transition period that is assumed to be characterized by increased sensitivity to reward. While there is growing research on reward processing in adolescents, investigations into the engagement of brain regions under different reward-related conditions in one sample of healthy adolescents, especially in a target age group, are missing. We aimed to identify brain regions preferentially activated in a reaction time task (monetary incentive delay (MID) task) and a simple guessing task (SGT) in a sample of 14-year-old adolescents (N = 54) using two commonly used reward paradigms. Functional magnetic resonance imaging was employed during the MID with big versus small versus no win conditions and the SGT with big versus small win and big versus small loss conditions. Analyses focused on changes in blood oxygen level-dependent contrasts during reward and punishment processing in anticipation and feedback phases. We found clear magnitude-sensitive response in reward-related brain regions such as the ventral striatum during anticipation in the MID task, but not in the SGT. This was also true for reaction times. The feedback phase showed clear reward-related, but magnitude-independent, response patterns, for example in the anterior cingulate cortex, in both tasks. Our findings highlight neural and behavioral response patterns engaged in two different reward paradigms in one sample of 14-year-old healthy adolescents and might be important for reference in future studies investigating reward and punishment processing in a target age group.

Functional dissociation of ongoing oscillatory brain states.

The state of a neural assembly preceding an incoming stimulus is assumed to modulate the processing of subsequently presented stimuli. The nature of this state can differ with respect to the frequency of ongoing oscillatory activity. Oscillatory brain activity of specific frequency range such as alpha (8-12 Hz) and gamma (above 30 Hz) band oscillations are hypothesized to play a functional role in cognitive processing. Therefore, a selective modulation of this prestimulus activity could clarify the functional role of these prestimulus fluctuations. For this purpose, we adopted a novel non-invasive brain-computer-interface (BCI) strategy to selectively increase alpha or gamma band activity in the occipital cortex combined with an adaptive presentation of visual stimuli within specific brain states. During training, oscillatory brain activity was estimated online and fed back to the participants to enable a deliberate modulation of alpha or gamma band oscillations. Results revealed that volunteers selectively increased alpha and gamma frequency oscillations with a high level of specificity regarding frequency range and localization. At testing, alpha or gamma band activity was classified online and at defined levels of activity, visual objects embedded in noise were presented instantly and had to be detected by the volunteer. In experiment I, the effect of two levels of prestimulus gamma band activity on visual processing was examined. During phases of increased gamma band activity significantly more visual objects were detected. In experiment II, the effect was compared against increased levels of alpha band activity. An improvement of visual processing was only observed for enhanced gamma band activity. Both experiments demonstrate the specific functional role of prestimulus gamma band oscillations for perceptual processing. We propose that the BCI method permits the selective modulation of oscillatory activity and the direct assessment of behavioral consequences to test for functional dissociations of different oscillatory brain states.

Corticocortical connections mediate primary visual cortex responses to auditory stimulation in the blind.

Blind individuals have to rely on nonvisual information to a greater extent than sighted to efficiently interact with the environment, and consequently exhibit superior skills in their spared modalities. These performance advantages are often paralleled by responses in the occipital cortex, which have been suggested to be essential for nonvisual processing in the blind. However, it is currently unclear through which pathways (i.e., thalamocortical or corticocortical connections) nonvisual information reaches the occipital cortex of the blind. Here, we used functional magnetic resonance imaging to study blind and matched sighted humans with an auditory discrimination paradigm and used dynamic causal modeling to investigate the effective connectivity underlying auditory activations in the primary visual cortex of blind volunteers. Model comparison revealed that a model connecting the medial geniculate nucleus (MGN), primary auditory cortex (A1), and primary visual cortex (V1) in a bidirectional manner outperformed all other models in both groups. Regarding inference on model parameters, we observed that basic auditory mechanisms (i.e., sensory input to MGN and connections from MGN to A1) did not differ significantly between the two groups. In contrast, we found clear evidence for stronger corticocortical connections from A1 to V1 in the blind, whereas results with regard to thalamocortical enhancement (from MGN to V1 and, in a control analysis, from the lateral geniculate nucleus to V1) were not consistent. These results suggest that plastic changes especially in corticocortical connectivity allow auditory information to evoke responses in the primary visual cortex of blind individuals.

Increased amygdala activation to emotional auditory stimuli in the blind.

Emotional signals are of pivotal relevance in social interactions. Neuroimaging and lesion studies have established an important role of the amygdala for the processing of these signals. While the human amygdala receives input from all sensory modalities, it is the visual modality that is most important for emotional aspects in social interactions. Consequently, amygdala involvement in visual emotional processing has been unequivocally established, whereas its role in auditory emotional processing is less clear. To investigate amygdala involvement in auditory emotional processing, we used functional magnetic resonance imaging in sighted and connatally blind volunteers, the latter of which lack visual experience during development but have outstanding capabilities to process auditory signals, which are their dominant source of information in social interactions. First, we observed a performance advantage of the connatally blind in auditory discrimination tasks that was paralleled by occipital cortex activation, which was not present in the sighted. More importantly, the blind not only showed robust selective activation in the amygdala to fearful and angry compared to neutral voices but also showed stronger activation to those stimuli than sighted participants. Higher amygdala activity for fearful items was further associated with individual performance in the blind, indicating that amygdala activation in the blind is not only driven by blindness per se but also by inter-individual differences in auditory capabilities. Our results indicate that the responsivity of the amygdala to emotional signals develops even in the absence of visual emotional experience and serves the sensory modality which is the most reliable source of emotional information.