Christine Wiebking

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.

GABA in the insula — a predictor of the neural response to interoceptive awareness

The insula has been identified as a key region involved in interoceptive awareness. Whilst imaging studies have investigated the neural activation patterns in this region involved in intero- and exteroceptive awareness, the underlying biochemical mechanisms still remain unclear. In order to investigate these, a well-established fMRI task targeting interoceptive awareness (heartbeat counting) and exteroceptive awareness (tone counting) was combined with magnetic resonance spectroscopy (MRS). Controlling for physiological noise, neural activity in the insula during intero- and exteroceptive awareness was confirmed in an independent data sample using the same fMRI design. Focussing on MRS values from the left insula and combining them with neural activity during intero- and exteroceptive awareness in the same healthy individuals, we demonstrated that GABA concentration in a region highly involved in interoceptive processing is correlated with neural responses to interoceptive stimuli, as opposed to exteroceptive stimuli. In addition, both GABA and interoceptive signal changes in the insula predicted the degree of depressed affect, as measured by the Beck Hopelessness Scale. On the one hand, the association between GABA concentration and neural activity during interoceptive awareness provides novel insight into the biochemical underpinnings of insula function and interoception. On the other, through the additional association of both GABA and neural activity during interoception with depressed affect, these data also bear potentially important implications for psychiatric disorders like depression and anxiety, where GABAergic deficits, altered insula function and abnormal affect coincide.

Abnormal body perception and neural activity in the insula in depression: An fMRI study of the depressed "material me"

Abstract Objectives. In addition to affective-cognitive symptoms, patients with major depressive disorder (MDD) suffer from somato-vegetative symptoms, suggesting abnormal interoceptive awareness of their “material me”. While recent imaging studies have extensively investigated affective-cognitive symptoms in MDD, the neural correlates of somato-vegetative symptoms and abnormal interoception remain unclear. Since the “material me” has been especially associated with the anterior insula in healthy subjects, we hypothesized abnormalities in this region during interoceptive awareness in MDD. Methods. We therefore investigated behavioural and neural correlates of interoception in healthy and depressed subjects using the Body Perception Questionnaire (BPQ) and a well established heartbeat perception task in fMRI. Results. MDD patients showed significantly higher scores in the BPQ and reduced neural activity during rest periods, particularly in the bilateral anterior insula. In contrast to healthy subjects, BPQ scores no longer correlated with activity during rest periods in the anterior insula. Both BPQ scores and left anterior insula signal changes correlated with depression severity. Conclusions. We demonstrate for the first time abnormal body perception and altered activity in the insula during rest in MDD. Our results suggest that these behavioural and neural abnormalities are closely related to these patients’ somato-vegetative abnormalities and their abnormal “material me”.

Associations of regional GABA and glutamate with intrinsic and extrinsic neural activity in humans—A review of multimodal imaging studies

The integration of multiple imaging modalities is becoming an increasingly well used research strategy for studying the human brain. The neurotransmitters glutamate and GABA particularly lend themselves towards such studies. This is because these transmitters are ubiquitous throughout the cortex, where they are the key constituents of the inhibition/excitation balance, and because they can be easily measured in vivo through magnetic resonance spectroscopy, as well as with select positron emission tomography approaches. How these transmitters underly functional responses measured with techniques such as fMRI and EEG remains unclear though, and was the target of this review. Consistently shown in the literature was a negative correlation between GABA concentrations and stimulus-induced activity within the measured region. Also consistently found was a positive correlation between glutamate concentrations and inter-regional activity relationships, both during tasks and rest. These findings are outlined along with results from populations with mental disorders to give an overview of what brain imaging has suggested to date about the biochemical underpinnings of functional activity in health and disease. We conclude that the combination of functional and biochemical imaging in humans is an increasingly informative approach that does however require a number of key methodological and interpretive issues be addressed before can meet its potential.

Involvement of glutamate in rest-stimulus interaction between perigenual and supragenual anterior cingulate cortex: a combined fMRI-MRS study.

The brain shows a high degree of activity at rest. The significance of this activity has come increasingly into focus. At present, however, the interaction between this activity and stimulus‐induced activity is not well defined. The interaction between a task‐negative (perigenual anterior cingulate cortex, pgACC) and task‐positive (supragenual anterior cingulate cortex, sgACC) region during a simple task was thus investigated using a combination of fMRI and MRS. Negative BOLD responses in the pgACC were found to show a unidirectional effective connectivity with task‐induced positive BOLD responses in the sgACC. This connectivity was shown to be related specifically with glutamate levels in the pgACC. These results demonstrate an interaction between deactivation from resting‐state and resting‐state glutamate levels in a task‐negative region (pgACC), and task‐induced activity in a task‐positive region (sgACC). This provides insight into the neuronal and biochemical mechanisms by means of which the resting state activity of the brain potentially impacts upon subsequent stimulus‐induced activity. Hum Brain Mapp, 2011.

Glutamate Concentration in the Medial Prefrontal Cortex Predicts Resting-State Cortical-Subcortical Functional Connectivity in Humans

Communication between cortical and subcortical regions is integral to a wide range of psychological processes and has been implicated in a number of psychiatric conditions. Studies in animals have provided insight into the biochemical and connectivity processes underlying such communication. However, to date no experiments that link these factors in humans in vivo have been carried out. To investigate the role of glutamate in individual differences in communication between the cortex – specifically the medial prefrontal cortex (mPFC) – and subcortical regions in humans, a combination of resting-state fMRI, DTI and MRS was performed. The subcortical target regions were the nucleus accumbens (NAc), dorsomedial thalamus (DMT), and periaqueductal grey (PAG). It was found that functional connectivity between the mPFC and each of the NAc and DMT was positively correlated with mPFC glutamate concentrations, whilst functional connectivity between the mPFC and PAG was negatively correlated with glutamate concentration. The correlations involving mPFC glutamate and FC between the mPFC and each of the DMT and PAG were mirrored by correlations with structural connectivity, providing evidence that the glutamatergic relationship may, in part, be due to direct connectivity. These results are in agreement with existing results from animal studies and may have relevance for MDD and schizophrenia.

Glutamate modulates resting state activity in the perigenual anterior cingulate cortex - A combined fMRI-MRS study

The perigenual anterior cingulate cortex (PACC) shows high resting state activity and is considered part of the default-mode network (DMN). However, the biochemical underpinnings of the PACCs high resting state activity remain unclear. While animal-based evidence points toward a role for the glutamatergic system, the modulation of the resting state activity level by itself as distinguished from stimulus-induced activity remains to be shown in humans. Using combined fMRI-MRS in healthy subjects, we here demonstrate that the PACC resting state concentration of glutamate is directly related to the level of resting state activity in the same region. In contrast, no such relationship could be detected during the anticipation of reward and punishment, nor in an independent control region (the left anterior insula). Taken together, our findings demonstrate for the first time the modulation of the PACC resting state activity level by the concentration of glutamate in the same regions. This contributes to a better understanding of the biochemical basis for the brains resting state activity as well as providing some clues regarding its apparent pathological upregulation in psychiatric disorders like the major depressive disorder.

Are emotions associated with activity during rest or interoception? An exploratory fMRI study in healthy subjects

Imaging studies investigating the default-mode network (DMN) of the brain revealed the phenomenon of elevated neural responses during periods of rest. This effect has been shown to be abnormally elevated in regions of the DMN concerning mood disorders like major depressive disorder (MDD). Since these disorders are accompanied by impaired emotional functioning, this leads to the suggestion of an association between activity during rest conditions and emotions, which remains to be demonstrated in a healthy and clinical population. Controlling for interoceptive processing, a process often closely connected to emotional functioning, we here demonstrate in an fMRI study of 30 healthy subjects the connection between activity during rest conditions in regions of the DMN and emotions in a psychologically, regionally, and stimulus specific way. Our findings provide further insight into the psychological functions underlying rest activity. Our findings in healthy subjects may also have future implications for a better understanding of mood disorders.

Negative childhood experiences alter a prefrontal-insular-motor cortical network in healthy adults: A preliminary multimodal rsfMRI-fMRI-MRS-dMRI study

Research in humans and animals has shown that negative childhood experiences (NCE) can have long‐term effects on the structure and function of the brain. Alterations have been noted in grey and white matter, in the brains resting state, on the glutamatergic system, and on neural and behavioural responses to aversive stimuli. These effects can be linked to psychiatric disorder such as depression and anxiety disorders that are influenced by excessive exposure to early life stressors. The aim of the current study was to investigate the effect of NCEs on these systems. Resting state functional MRI (rsfMRI), aversion task fMRI, glutamate magnetic resonance spectroscopy (MRS), and diffusion magnetic resonance imaging (dMRI) were combined with the Childhood Trauma Questionnaire (CTQ) in healthy subjects to examine the impact of NCEs on the brain. Low CTQ scores, a measure of NCEs, were related to higher resting state glutamate levels and higher resting state entropy in the medial prefrontal cortex (mPFC). CTQ scores, mPFC glutamate and entropy, correlated with neural BOLD responses to the anticipation of aversive stimuli in regions throughout the aversion‐related network, with strong correlations between all measures in the motor cortex and left insula. Structural connectivity strength, measured using mean fractional anisotropy, between the mPFC and left insula correlated to aversion‐related signal changes in the motor cortex. These findings highlight the impact of NCEs on multiple inter‐related brain systems. In particular, they highlight the role of a prefrontal‐insular‐motor cortical network in the processing and responsivity to aversive stimuli and its potential adaptability by NCEs. Hum Brain Mapp 36:4622–4637, 2015.

Preceding attention and the dorsomedial prefrontal cortex: Process specificity versus domain dependence

The dorsomedial prefrontal cortex (DMPFC) has been shown to be involved in attending different states, all including a strong emotional component. It remains unclear, though, whether neural activity in the DMPFC is predominantly determined by either a particular domain, as emotional stimuli, or by a specific process, as attention. Here, we used functional magnetic resonance imaging to test the alternative hypotheses of domain‐ versus process‐specificity in DMPFC. Subjects had to perceive pictures from three different domains, sexual, emotional, and neutral stimuli, in both a nonattended, i.e., unexpected, and attended, i.e., expected mode. Our results show DMPFC activation during attended, i.e., expected stimulus perception when compared with nonattended, i.e., unexpected stimuli perception. DMPFC activation and corresponding behavioral changes (reaction time, subjective ratings) were observed in all three domains, sexual, emotional, and neutral stimuli. As opposed to those process‐specific effects that were found predominantly in posterior DMPFC, a process by domain interaction was found to be characteristic for more anterior parts of the DMPFC. Taken together, our findings favour the hypothesis that neural activity in the posterior DMPFC is determined by a specific process, i.e., attending stimuli, and thus characterized by process‐specificity rather than by a particular domain, i.e., sexual, emotional, or neutral stimuli, reflecting domain‐specificity. This suggests that the anterior and posterior DMPFC is involved in the process of attending mental states while remaining more (posterior DMPFC) or less (anterior DMPFC) independent of the type or domain of the respective stimulus. Hum Brain Mapp, 2009.