Heterosexual Male Perpetrators of Childhood Sexual Abuse: A Preliminary Neuropsychiatric Model

This paper presents data from a series of prelimary neuropsychiatric studies, including neuropsychological, personality, sexual history, plethysmographic and neuroimaging investigations, on a sample of 22 male, heterosexual, nonexclusive pedophiles and 24 demographically similar healthy controls. A psychobiological model of pedophilia is proposed, positing that early childhood sexual abuse leads to neurodevelopmental abnormalities in the temporal regions mediating sexual arousal and erotic discrimination and the frontal regions mediating the cognitive aspects of sexual desire and behavioral inhibition. In this way, pedophiles develop deviant pedophilic arousal. Subsequently, if there is comorbid personality pathology, specifically sociopathy and cognitive distortions, there will be failure to inhibit pedophilic behavior.     

The functional neuroanatomy of male psychosexual and physiosexual arousal: A quantitative meta‐analysis

Reproductive behavior is mandatory for conservation of species and mediated by a state of sexual arousal (SA), involving both complex mental processes and bodily reactions. An early neurobehavioral model of SA proposes cognitive, emotional, motivational, and autonomic components. In a comprehensive quantitative meta‐analysis on previous neuroimaging findings, we provide here evidence for distinct brain networks underlying psychosexual and physiosexual arousal. Psychosexual (i.e., mental sexual) arousal recruits brain areas crucial for cognitive evaluation, top‐down modulation of attention and exteroceptive sensory processing, relevance detection and affective evaluation, as well as regions implicated in the representation of urges and in triggering autonomic processes. In contrast, physiosexual (i.e., physiological sexual) arousal is mediated by regions responsible for regulation and monitoring of initiated autonomic processes and emotions and for somatosensory processing. These circuits are interconnected by subcortical structures (putamen and claustrum) that provide exchange of sensorimotor information and crossmodal processing between and within the networks. Brain deactivations may imply attenuation of introspective processes and social cognition, but be necessary to release intrinsic inhibition of SA. Hum Brain Mapp 35:1404–1421, 2014. © 2013 Wiley Periodicals, Inc.     

Structural insights into aberrant cortical morphometry and network organization in psychogenic erectile dysfunction

Functional neuroimaging studies have revealed abnormal brain dynamics of male sexual arousal (SA) in psychogenic erectile dysfunction (pED). However, the neuroanatomical correlates of pED are still unclear. In this work, we obtained cortical thickness (CTh) measurements from structural magnetic resonance images of 40 pED patients and 39 healthy control subjects. Abnormalities in CTh related to pED were explored using a scale space search based brain morphometric analysis. Organizations of brain structural covariance networks were analyzed as well. Compared with healthy men, pED patients showed significantly decreased CTh in widespread cortical regions, most of which were previously reported to show abnormal dynamics of male SA in pED, such as the medial prefrontal, orbitofrontal, cingulate, inferotemporal, and insular cortices. CTh reductions in these areas were found to be significantly correlated with male sexual functioning degradation. Moreover, pED patients showed decreased interregional CTh correlations from the right lateral orbitofrontal cortex to the right supramarginal gyrus and the left angular cortex, implying disassociations between the cognitive, motivational, and inhibitory networks of male SA in pED. This work provides structural insights on the complex phenomenon of psychogenic sexual dysfunction in men, and suggests a specific vulnerability factor, possibly as an extra “organic” factor, that may play an important role in pED. Hum Brain Mapp 36:4469–4482, 2015. © 2015 Wiley Periodicals, Inc .     

Neural processing associated with cognitive empathy in pedophilia and child sexual offending

Behavioral studies found evidence for superior cognitive empathy (CE) in pedophilic men without a history of child sexual offending (P − CSO) compared to pedophilic men with a history of child sexual offending (P + CSO). Functional magnetic resonance imaging (fMRI) studies also point to differences between P − CSO and P + CSO. Neural processing associated with CE has not yet been investigated. Therefore, the present study aimed to explore the neural correlates of CE in subjects with pedophilia with (P + CSO) and without (P − CSO) child sexual offending. 15 P + CSO, 15 P − CSO and 24 teleiophilic male controls (TC) performed a CE task during fMRI. We observed reduced activation in the left precuneus (Pcu) and increased activation in the left anterior cingulate cortex (ACC) in P − CSO compared to P + CSO. P − CSO also showed stronger connectivity between these regions, which might reflect a top-down modulation of the Pcu by the ACC toward an increased self-focused emotional reaction in social situations. There was also evidence for increased right superior temporal gyrus activation in P − CSO that might constitute a potentially compensatory recruitment due to the dampened Pcu activation. These findings provide first evidence for altered neural processing of CE in P − CSO and underline the importance of addressing CE in pedophilia and CSO in order to uncover processes relevant to effective prevention of child sexual abuse.     

The neurodevelopmental differences of increasing verbal working memory demand in children and adults

Working memory (WM) – temporary storage and manipulation of information in the mind – is a key component of cognitive maturation, and structural brain changes throughout development are associated with refinements in WM. Recent functional neuroimaging studies have shown that there is greater activation in prefrontal and parietal brain regions with increasing age, with adults showing more refined, localized patterns of activations. However, few studies have investigated the neural basis of verbal WM development, as the majority of reports examine visuo-spatial WM.We used fMRI and a 1-back verbal WM task with six levels of difficulty to examine the neurodevelopmental changes in WM function in 40 participants, twenty-four children (ages 9–15 yr) and sixteen young adults (ages 20–25 yr). Children and adults both demonstrated an opposing system of cognitive processes with increasing cognitive demand, where areas related to WM (frontal and parietal regions) increased in activity, and areas associated with the default mode network decreased in activity. Although there were many similarities in the neural activation patterns associated with increasing verbal WM capacity in children and adults, significant changes in the fMRI responses were seen with age. Adults showed greater load-dependent changes than children in WM in the bilateral superior parietal gyri, inferior frontal and left middle frontal gyri and right cerebellum. Compared to children, adults also showed greater decreasing activation across WM load in the bilateral anterior cingulate, anterior medial prefrontal gyrus, right superior lateral temporal gyrus and left posterior cingulate. These results demonstrate that while children and adults activate similar neural networks in response to verbal WM tasks, the extent to which they rely on these areas in response to increasing cognitive load evolves between childhood and adulthood.     

Brain processing of visual sexual stimuli in human males

Despite its critical sociobiological importance, the brain processing of visual sexual stimuli has not been characterized precisely in human beings. We used Positron Emission Tomography (PET) to investigate responses of regional cerebral blood flow (rCBF) in nine healthy males presented with visual sexual stimuli of graded intensity. Statistical Parametric Mapping was used to locate brain regions whose activation was associated with the presentation of the sexual stimuli and was correlated with markers of sexual arousal. The claustrum, a region whose function had been unclear, displayed one of the highest activations. Additionally, activations were recorded in paralimbic areas (anterior cingulate gyrus, orbito-frontal cortex), in the striatum (head of caudate nucleus, putamen), and in the posterior hypothalamus. By contrast, decreased rCBF was observed in several temporal areas. Based on these results, we propose a model of the brain processes mediating the cognitive, emotional, motivational, and autonomic components of human male sexual arousal.     

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.     

Atypical neuronal activation during a spatial working memory task in 13‐year‐old very preterm children

Children born very preterm (VP; <32 weeks' gestational age) are at risk for unfavorable outcomes in several cognitive domains, including spatial working memory (WM). The underlying neural basis of these cognitive impairments is poorly understood. We investigated differences in neuronal activation during spatial WM using a backward span (BS) task relative to a control (C) task in 45 VP children and 19 term‐born controls aged 13 years. VP children showed significantly more activation in the bilateral superior frontal gyrus and significantly less activation in the left parahippocampal gyrus compared with controls. We further explored the distinct contributions of maintenance and manipulation processes of WM using forward span (FS)>C and BS > FS, respectively. There were no significant group differences in neuronal activation for FS > C. However, BS > FS revealed that VP children had significantly greater activation in the left middle frontal gyrus, in the left superior parietal gyrus and right cerebellar tonsil, and significantly less activation in the right precentral and postcentral gyrus and left insula compared with controls. Taken together these results suggest that VP children at 13 years of age show an atypical neuronal activation during spatial WM, specifically related to manipulation of spatial information in WM. It is unclear whether these findings reflect delayed maturation and/or recruitment of alternative neuronal networks as a result of neuroplasticity. Hum Brain Mapp 38:6172–6184, 2017. © 2017 Wiley Periodicals, Inc.     

Decomposing metaphor processing at the cognitive and neural level through functional magnetic resonance imaging

Prior neuroimaging studies on metaphor comprehension have tended to focus on the role of the right hemisphere, without reaching consensus and leaving aside the functional architecture of this process. The present work aimed to break down metaphor comprehension into its functional components. The study rationale is two-fold: on the one hand, the large-scale network model as emerging in cognitive neuroscience led us to a consideration of metaphor as supported by a distributed and bilateral network; on the other hand, we based on the accounts of figurative language put forward in pragmatics and cognitive science to postulate a decomposition of such a network into multiple sub-systems. During scanning, participants implicitly processed metaphorical (familiar and unfamiliar) and non-metaphorical passages, while being explicitly involved in an adjective matching task to be performed after reading the target passages. Several regions showed greater activity to metaphors as compared to non-metaphors, including left and right inferior frontal gyrus, right superior temporal gyrus, left angular gyrus, and anterior cingulate. This pattern of activations, markedly bilateral, can be decomposed into circumscribed functional sub-systems mediating different aspects of metaphor resolution, as foreseen in the pragmatic and cognitive literature: (a) the conceptual/pragmatic machinery in the bilateral inferior frontal gyrus and in the left angular gyrus, which supports the integration of linguistic material and world knowledge in context; (b) the attentional component in the anterior cingulate and prefrontal areas, which is set to monitor and filter for the relevant aspects of context and for the appropriate meanings; (c) the Theory of Mind system along the right superior temporal sulcus, which deals with the recognition of speakers' communicative intentions and is more extensively activated by unfamiliar metaphors. The results have several implications for the field of neuropragmatics, especially on the neuropsychological side and on the right hemisphere hypothesis.     

Brain processing of visual sexual stimuli in treated and untreated hypogonadal patients

OBJECTIVE: Although various brain regions have been shown to respond to the presentation of visual sexual stimuli (VSS), whether these regions are specifically mediating sexual arousal or whether they mediate general emotional or motivational arousal is unknown. To clarify this issue, our purpose was to map the regions where the response to VSS was related to plasma testosterone. Specific objectives were (i) to identify regions that respond differentially to VSS in untreated hypogonadal patients compared with healthy controls and (ii) to identify in hypogonadal patients the regions that respond differentially to VSS as a function of therapeutically induced increased testosterone levels. METHOD: In nine male hypogonadal patients, in the same patients under treatment, and in eight healthy males, we used Positron Emission Tomography to investigate responses of regional cerebral blood flow to VSS. Statistical Parametric Mapping was used to locate regions that demonstrated a differential response. RESULTS: Regions responding differentially both in untreated patients compared with controls and in untreated patients compared with themselves under treatment were the right orbitofrontal cortex, insula and claustrum, where the activation was higher in controls than in untreated patients and where activation increased under treatment, and the left inferior frontal gyrus, that demonstrated a deactivation only in controls and in patients under treatment. That these responses appear to depend on testosterone indicates that these regions mediate sexual arousal and not only a process of general emotional or motivational arousal.     

Acupuncture at the Taixi （KI3） acupoint activates cerebral neurons in elderly patients with mild cognitive impairment

Our previous ifndings have demonstrated that acupuncture at the Taixi （KI3） acupoint in healthy youths can activate neurons in cognitive-related cerebral cortex. Here, we investigated whether acupuncture at this acupoint in elderly patients with mild cognitive impairment can also activate neurons in these regions. Resting state and task-related functional magnetic resonance imaging showed that the pinprick senstation of acupuncture at the Taixi acupoint differed signiifcantly between elderly patients with mild cognitive impairment and healthy elderly controls. Results showed that 20 brain regions were activated in both groups of participants, including the bi-lateral anterior cingulate gyrus （Brodmann areas [BA] 32, 24）, left medial frontal cortex （BA 9, 10, 11）, left cuneus （BA 19）, left middle frontal gyrus （BA 11）, left lingual gyrus （BA 18）, right medial frontal gyrus （BA 11）, bilateral inferior frontal gyrus （BA 47）, left superior frontal gyrus （BA11）, right cuneus （BA 19, 18）, right superior temporal gyrus （BA 38）, left subcallosal gyrus （BA 47）, bilateral precuneus （BA 19）, right medial frontal gyrus （BA 10）, right superior frontal （BA 11）, left cingulate gyrus （BA 32）, left precentral gyrus （BA 6）, and right fusiform gyrus （BA 19）. These results suggest that acupuncture at the Taixi acupoint in elderly patients with mild cogni-tive impairment can also activate some brain regions.     

Listening under difficult conditions: An activation likelihood estimation meta‐analysis

The brain networks supporting speech identification and comprehension under difficult listening conditions are not well specified. The networks hypothesized to underlie effortful listening include regions responsible for executive control. We conducted meta‐analyses of auditory neuroimaging studies to determine whether a common activation pattern of the frontal lobe supports effortful listening under different speech manipulations. Fifty‐three functional neuroimaging studies investigating speech perception were divided into three independent Activation Likelihood Estimate analyses based on the type of speech manipulation paradigm used: Speech‐in‐noise (SIN, 16 studies, involving 224 participants); spectrally degraded speech using filtering techniques (15 studies involving 270 participants); and linguistic complexity (i.e., levels of syntactic, lexical and semantic intricacy/density, 22 studies, involving 348 participants). Meta‐analysis of the SIN studies revealed higher effort was associated with activation in left inferior frontal gyrus (IFG), left inferior parietal lobule, and right insula. Studies using spectrally degraded speech demonstrated increased activation of the insula bilaterally and the left superior temporal gyrus (STG). Studies manipulating linguistic complexity showed activation in the left IFG, right middle frontal gyrus, left middle temporal gyrus and bilateral STG. Planned contrasts revealed left IFG activation in linguistic complexity studies, which differed from activation patterns observed in SIN or spectral degradation studies. Although there were no significant overlap in prefrontal activation across these three speech manipulation paradigms, SIN and spectral degradation showed overlapping regions in left and right insula. These findings provide evidence that there is regional specialization within the left IFG and differential executive networks underlie effortful listening.     

Neural mechanisms of autonomic, affective, and cognitive integration

Influential theoretical models propose a central role for afferent information from the body in the expression of emotional feeling states. Feedback representations of changing states of bodily arousal influence learning and facilitate concurrent and prospective decision-making. Functional neuroimaging studies have increased understanding of brain mechanisms that generate changes in autonomic arousal during behavior and those which respond to internal feedback signals to influence subjective feeling states. In particular, anterior cingulate cortex is implicated in generating autonomic changes, while insula and orbitofrontal cortices may be specialized in mapping visceral responses. Independently, ventromedial prefrontal cortex is recognized to support processes of internal (self-) reference that predominate in states of rest and disengagement and which putatively serve as a benchmark for dynamic interactions with the environment. Lesion data further highlight the integrated role of these cortical regions in autonomic and motivational control. In computational models of control, forward (efference copies) and inverse models are proposed to enable prediction and correction of action and, by extension, the interpretation of the behavior of others. It is hypothesized that the neural substrate for these processes during motivational and affective behavior lies within the interactions of anterior cingulate, insula, and orbitofrontal cortices. Generation of visceral autonomic correlates of control reinforce experiential engagement in simulatory models and underpin concepts such as somatic markers to bridge the dualistic divide.     

The Effects of Acute Transcranial Direct Current Stimulation on Attentional Bias in Pedophilic Disorder: A Preregistered Pilot Study

ObjectivesIndividuals with pedophilic disorder (PD) experience personal and interpersonal difficulties and are at risk of sexually offending against children. As such, innovative and empirically validated treatments are needed. Recent studies have indicated that men who have sexually offended against children (SOC) with PD display an automatic attention bias for child-related stimuli as well as reduced activity in the dorsolateral prefrontal cortex (dlPFC), a brain area involved in cognitive control, including control over sexual arousal. In this preregistered pilot study, we are the first to investigate whether acutely increasing prefrontal activity could reduce the putative pedophilic attention bias.Materials and MethodsWe delivered a single 20-min session of active anodal versus sham transcranial direct current stimulation (tDCS) over the left dlPFC to 16 SOC with PD and 16 matched healthy controls, while they performed a task requiring controlled attention to computer-generated images of clothed and nude children and adults. We collected responses unobtrusively by recording eye movements.ResultsOur results did not support the presence of the expected automatic attention bias across outcome measures. Nonetheless, we found a response facilitation with child targets in patients and, unexpectedly, in controls, likely due to unwanted salience effects. Active versus sham tDCS reduced this bias across groups, as indicated by a significant group*condition interaction (p = 0.04). However, no attentional bias and no tDCS effects on attentional responses to child and adult images emerged following tDCS.ConclusionsThese results suggest enhanced cognitive control in response to salient stimuli during active tDCS. Thus, to assist future studies on neuromodulation in PD, we provide suggestions for design improvement.     

Brain pathology in pedophilic offenders: evidence of volume reduction in the right amygdala and related diencephalic structures

CONTEXT: Pedophilic crime causes considerable public concern, but no causative factor of pedophilia has yet been pinpointed. In the past, etiological theories postulated a major impact of the environment, but recent studies increasingly emphasize the role of neurobiological factors, as well. However, the role of alterations in brain structures that are crucial in the development of sexual behavior has not yet been systematically studied in pedophilic subjects. OBJECTIVE: To examine whether pedophilic perpetrators show structural neuronal deficits in brain regions that are critical for sexual behavior and how these deficits relate to criminological characteristics. DESIGN: Amygdalar volume and gray matter of related structures that are critical for sexual development were compared in 15 nonviolent male pedophilic perpetrators (forensic inpatients) and 15 controls using complementary morphometric analyses (voxel-based morphometry and volumetry). Psychosocial adjustment and sexual offenses were also assessed. RESULTS: Pedophilic perpetrators showed a significant decrease of right amygdalar volume, compared with healthy controls (P = .001). We observed reduced gray matter in the right amygdala, hypothalamus (bilaterally), septal regions, substantia innominata, and bed nucleus of the striae terminalis. In 8 of the 15 perpetrators, enlargement of the anterior temporal horn of the right lateral ventricle that adjoins the amygdala could be recognized by routine qualitative clinical assessment. Smaller right amygdalar volumes were correlated with the propensity to commit uniform pedophilic sexual offenses exclusively (P = .006) but not with age (P = .89). CONCLUSIONS: Pedophilic perpetrators show structural impairments of brain regions critical for sexual development. These impairments are not related to age, and their extent predicts how focused the scope of sexual offenses is on uniform pedophilic activity. Subtle defects of the right amygdala and closely related structures might be implicated in the pathogenesis of pedophilia and might possibly reflect developmental disturbances or environmental insults at critical periods.     

A parametric manipulation of factors affecting task-induced deactivation in functional neuroimaging

Task-induced deactivation (TID) refers to a regional decrease in blood flow during an active task relative to a "resting" or "passive" baseline. We tested the hypothesis that TID results from a reallocation of processing resources by parametrically manipulating task difficulty within three factors: target discriminability, stimulus presentation rate, and short-term memory load. Subjects performed an auditory target detection task during functional magnetic resonance imaging (fMRI), responding to a single target tone or, in the short-term memory load conditions, to target sequences. Seven task conditions (a common version and two additional levels for each of the three factors) were each alternated with "rest" in a block design. Analysis of covariance identified brain regions in which TID occurred. Analyses of variance identified seven regions (left anterior cingulate/superior frontal gyrus, left middle frontal gyrus, right anterior cingulate gyrus, left and right posterior cingulate gyrus, left posterior parieto-occipital cortex, and right precuneus) in which TID magnitude varied across task levels within a factor. Follow-up tests indicated that for each of the three factors, TID magnitude increased with task difficulty. These results suggest that TID represents reallocation of processing resources from areas in which TID occurs to areas involved in task performance. Short-term memory load and stimulus rate also predict suppression of spontaneous thought, and many of the brain areas showing TID have been linked with semantic processing, supporting claims that TID may be due in part to suspension of spontaneous semantic processes that occur during "rest" (Binder et al., 1999). The concept that the typical "resting state" is actually a condition characterized by rich cognitive activity has important implications for the design and analysis of neuroimaging studies.     

A cortical network for directed attention and unilateral neglect

Unilateral neglect reflects a disturbance in the spatial distribution of directed attention. A review of unilateral neglect syndromes in monkeys and humans suggests that four cerebral regions provide an integrated network for the modulation of directed attention within extrapersonal space. Each component region has a unique functional role that reflects its profile of anatomical connectivity, and each gives rise to a different clinical type of unilateral neglect when damaged. A posterior parietal component provides an internal sensory map and perhaps also a mechanism for modifying the extent of synaptic space devoted to specific portions of the external world; a limbic component in the cingulate gyrus regulates the spatial distribution of motivational valence; a frontal component coordinates the motor programs for exploration, scanning, reaching, and fixating; and a reticular component provides the underlying level of arousal and vigilance. This hypothetical network requires at least three complementary and interacting representations of extrapersonal space: a sensory representation in posterior parietal cortex, a schema for distributing exploratory movements in frontal cortex, and a motivational map in the cingulate cortex. Lesions in only one component of this network yield partial unilateral neglect syndromes, while those that encompass all the components result in profound deficits that transcend the mass effect of the larger lesion. This network approach to the localization of complex functions offers an alternative to more extreme approaches, some of which stress an exclusive concentration of function within individual centers in the brain and others which advocate a more uniform (equipotential or holistic) distribution. In human beings, unilateral neglect syndromes are more frequent and severe after lesions in the right hemisphere. Also, right hemisphere mechanisms appear more effective in the execution of attentional tasks. Furthermore, the attentional functions of the right hemisphere span both hemispaces, while the left hemisphere seems to contain the neural apparatus mostly for contralateral attention. This evidence indicates that the right hemisphere of dextrals has a functional specialization for the distribution of directed attention within extrapersonal space.     

Interconnected large-scale systems for three fundamental cognitive tasks revealed by functional MRI

The specific brain areas required to execute each of three fundamental cognitive tasks - object naming, same-different discrimination, and integer computation - are determined by whole-brain functional magnetic resonance imaging (fMRI) using a novel technique optimized for the isolation of neurocognitive systems. This technique (1) conjoins the activity associated with identical or nearly identical tasks performed in multiple sensory modalities (conjunction) and (2) isolates the activity conserved across multiple subjects (conservation). Cortical regions isolated by this technique are, thus, presumed associated with cognitive functions that are both distinguished from primary sensory processes and from individual differences. The object-naming system consisted of four brain areas: left inferior frontal gyrus, Brodmann's areas (BAs) 45 and 44; left superior temporal gyrus, BA 22; and left medial frontal gyrus, BA 6. The same-different discrimination system consisted of three brain areas: right inferior parietal lobule, BA 40; right precentral gyrus, BA 6; and left medial frontal gyrus, BA 6. The integer computation system consisted of five brain areas: right middle frontal gyrus, BA 6; right precentral gyrus, BA 6; left inferior parietal lobule, BA 40; left inferior frontal gyrus, BA 44; and left medial frontal gyrus, BA 6. All three neurocognitive systems shared one common cortical region, the left medial frontal gyrus, the object-naming and integer computation systems shared the left inferior frontal gyrus, and the integer computation and same-different discrimination systems shared the right precentral gyrus. These results are consistent with connectionist models of cognitive processes where specific sets of remote brain areas are assumed to be transiently bound together as functional units to enable these functions, and further suggest a superorganization of neurocognitive systems where single brain areas serve as elements of multiple functional systems.     

Regional cerebral blood flow changes associated with clitorally induced orgasm in healthy women

There is a severe lack of knowledge regarding the brain regions involved in human sexual performance in general, and female orgasm in particular. We used [15O]-H2O positron emission tomography to measure regional cerebral blood flow (rCBF) in 12 healthy women during a nonsexual resting state, clitorally induced orgasm, sexual clitoral stimulation (sexual arousal control) and imitation of orgasm (motor output control). Extracerebral markers of sexual performance and orgasm were rectal pressure variability (RPstd) and perceived level of sexual arousal (PSA). Sexual stimulation of the clitoris (compared to rest) significantly increased rCBF in the left secondary and right dorsal primary somatosensory cortex, providing the first account of neocortical processing of sexual clitoral information. In contrast, orgasm was mainly associated with profound rCBF decreases in the neocortex when compared with the control conditions (clitoral stimulation and imitation of orgasm), particularly in the left lateral orbitofrontal cortex, inferior temporal gyrus and anterior temporal pole. Significant positive correlations were found between RPstd and rCBF in the left deep cerebellar nuclei, and between PSA and rCBF in the ventral midbrain and right caudate nucleus. We propose that decreased blood flow in the left lateral orbitofrontal cortex signifies behavioural disinhibition during orgasm in women, and that deactivation of the temporal lobe is directly related to high sexual arousal. In addition, the deep cerebellar nuclei may be involved in orgasm-specific muscle contractions while the involvement of the ventral midbrain and right caudate nucleus suggests a role for dopamine in female sexual arousal and orgasm.