Abnormal Sensory Perception Research Articles

Dysregulation of parvalbumin expression and neurotransmitter imbalance in the auditory cortex of the BTBR mouse model of autism spectrum disorder.

Individuals diagnosed with autism spectrum disorder (ASD) frequently exhibit abnormalities in auditory perception, a phenomenon potentially attributed to alterations in the excitatory and inhibitory cells constituting cortical circuits. However, the exact genetic factors and cell types affected by ASD remain unclear. The present study investigated the balance of excitatory and inhibitory activity in the auditory cortex using BTBR T+ Itpr3tf/J (BTBR) mice, a well-established model for autism research. Our investigation unveiled a reduction in parvalbumin-positive (PV+) neurons within the AC of BTBR mice. Remarkably, in vivo magnetic resonance spectroscopy studies disclosed an elevation in glutamate (Glu) levels alongside a decrement in γ-aminobutyric acid (GABA) levels in this cortical region. Additionally, transcriptomic analysis of the mouse model facilitated the classification of several ASD-associated genes based on their cellular function and pathways. By comparing autism risk genes with RNA transcriptome sequencing data from the ASD mouse model, we identified the recurrent target gene Scn1a and performed validation. Intriguingly, we uncovered the specific expression of Scn1a in cortical inhibitory neurons. These findings hold significant value for understanding the underlying neural mechanisms of abnormal sensory perception in animal models of ASD.

A multidimensional investigation of the relationship between skin-mediated somatosensory signals, emotion regulation and behavior problems in autistic children.

Autistic children may have abnormal sensory perception, emotion dysregulation and behavior problems. The aim of this cross-sectional study was to explore the relationship between skin-mediated somatosensory signals and emotion/behavior difficulties in autistic children and adolescents, in comparison typically developing peers (TDP). Thirty-eight autistic children and adolescents and 34 TDP completed a multidimensional assessment consisting of the measurement of somatosensory thresholds of touch, pain and temperature, a task on emotion knowledge and parent-reported questionnaires on sensory reactivity, emotion regulation and behavior. Autistic children had higher pain sensitivity, less sensory reactive behaviors and more behavior problems than their TDP. In contrast to TDP, several somatosensory thresholds of autistic children correlated with emotion regulation and behavior problems. Sensory dysfunction may affect the development of emotional processing and behavior in autistic children and adolescents. This knowledge can lay the foundation for future studies on co-occurring alterations in corresponding neural networks and for the implementation of early interventions, including sensory rehabilitation therapy, for promoting regulated behaviors in autistic children and adolescents.

Protocolo diagnóstico de las parestesias y disestesias

Paresthesias are abnormal sensory perceptions in the absence of specific sensory stimuli whereas dysesthesias are abnormal perceptions of real sensory stimuli. When a patient presents with paresthesias and dysesthesias, the manner in which the symptoms started must first be determined and a neurological examination be performed to determine if the abnormality is central or peripheral and if it requires urgent, time-sensitive care (vascular symptoms, spinal cord injuries, acute inflammatory demyelinating polyradiculopathy). If the paresthesia or dysesthesia affect the majority of a limb or if they are associated with signs of cortical dysfunction (hemianopia, sensory extinction, etc.) or signs of primary motor neuron involvement (hyperreflexia, clonus, or extension plantar reflex), they would initially point to a central abnormality. On the other hand, if the paresthesia or dysesthesia is limited to part of a limb and the area affected is concordant with the skin area innervated by one or several sensory roots of the spinal nerves (dermatome) or by one or various sensory skin nerves and, on the neurological examination, there are no signs of primary motor neuron involvement (normal reflexes, areflexia, hyporeflexia, flexion plantar reflex), they would initially point to a peripheral abnormality.

Perspectives on pain in Down syndrome.

Down syndrome (DS) or trisomy 21 is a genetic condition often accompanied by chronic pain caused by congenital abnormalities and/or conditions, such as osteoarthritis, recurrent infections, and leukemia. Although DS patients are more susceptible to chronic pain as compared to the general population, the pain experience in these individuals may vary, attributed to the heterogenous structural and functional differences in the central nervous system, which might result in abnormal pain sensory information transduction, transmission, modulation, and perception. We tried to elaborate on some key questions and possible explanations in this review. Further clarification of the mechanisms underlying such abnormal conditions induced by the structural and functional differences is needed to help pain management in DS patients.

Characterisation of Physiological Responses to Odours in Autism Spectrum Disorders: A Preliminary Study

Abnormal sensory perception is among the earliest symptoms of autism spectrum disorders (ASD). Despite mixed findings, olfactory perception seems to be altered in ASD. There is also evidence that automatic responses to odours can serve as biomarkers of ASD. However, this potential use of odour-based biomarkers for ASD is still underexplored. In this study, we aimed to investigate whether physiological responses to social and non-social odours, measured with electrocardiography (ECG) and facial electromyography (EMG), can be used to characterise and predict ASD in adults. For that, we extracted 32 signal features from a previously collected database of 11 adults with ASD and 48 adults with typical development (TD). Firstly, non-parametric tests were performed, showing significant differences between the ASD and the TD groups in 10 features. Secondly, a k-nearest-neighbour classifier with a leave-one-out strategy was employed, obtaining an F1-score of 67%. Although caution is needed due to the small sample size, this study provides preliminary evidence supporting the use of physiological responses to social and non-social odours as a potential diagnostic tool for ASD in adults.

Prediction Model for Sensory Perception Abnormality in Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by heterogeneous clinical phenotypes. Patients often experience abnormal sensory perception, which may further affect the ASD core phenotype, significantly and adversely affecting their quality of life. However, biomarkers for the diagnosis of ASD sensory perception abnormality are currently elusive. We sought to identify potential biomarkers related to ASD sensory perception abnormality to construct a prediction model that could facilitate the early identification of and screening for ASD. Differentially expressed genes in ASD were obtained from the Gene Expression Omnibus database and were screened for genes related to sensory perception abnormality. After enrichment analysis, the random forest method was used to identify disease-characteristic genes. A prediction model was constructed with an artificial neural network. Finally, the results were validated using data from the dorsal root ganglion, cerebral cortex, and striatum of the BTBR T+ Itpr3tf/J (BTBR) ASD mouse model. A total of 1869 differentially expressed genes in ASD were screened, among which 16 genes related to sensory perception abnormality were identified. According to enrichment analysis, these 16 genes were mainly related to actin, cholesterol metabolism, and tight junctions. Using random forest, 15 disease-characteristic genes were screened for model construction. The area under the curve of the training set validation result was 0.999, and for the model function validation, the result was 0.711, indicating high accuracy. The validation of BTBR mice confirmed the reliability of using these disease-characteristic genes for prediction of ASD. In conclusion, we developed a highly accurate model for predicting ASD sensory perception abnormality from 15 disease-characteristic genes. This model provides a new method for the early identification and diagnosis of ASD sensory perception abnormality.

Abnormal sensory perception masks behavioral performance of Grin1 knockdown mice.

The development and function of sensory systems require intact glutamatergic neurotransmission. Changes in touch sensation and vision are common symptoms in autism spectrum disorders, where altered glutamatergic neurotransmission is strongly implicated. Further, cortical visual impairment is a frequent symptom of GRIN disorder, a rare genetic neurodevelopmental disorder caused by pathogenic variants of GRIN genes that encode NMDA receptors. We asked if Grin1 knockdown mice (Grin1KD), as a model of GRIN disorder, had visual impairments resulting from NMDA receptor deficiency. We discovered that Grin1KD mice had deficient visual depth perception in the visual cliff test. Since Grin1KD mice are known to display robust changes in measures of learning, memory, and emotionality, we asked whether deficits in these higher-level processes could be partly explained by their visual impairment. By changing the experimental conditions to improve visual signals, we observed significant improvements in the performance of Grin1KD mice in tests that measure spatial memory, executive function, and anxiety. We went further and found destabilization of the outer segment of retina together with the deficient number and size of Meissner corpuscles (mechanical sensor) in the hind paw of Grin1KD mice. Overall, our findings suggest that abnormal sensory perception can mask the expression of emotional, motivational and cognitive behavior of Grin1KD mice. This study demonstrates new methods to adapt routine behavioral paradigms to reveal the contribution of vision and other sensory modalities in cognitive performance.

Transcriptomic analysis supports collective endometrial cell migration in the pathogenesis of adenomyosis

Research questionAdenomyosis is a common uterine disorder of uncertain causes. Can transcriptomic analyses of the endometrium and myometrium reveal potential mechanisms underlying adenomyosis pathogenesis? DesignTranscriptomic profiles of eutopic endometrium and myometrium from women with and without diffuse adenomyosis and with symptomatic FIGO type 2–5 fibroids in the proliferative phase of the menstrual cycle were assessed using RNA sequencing and bioinformatic analysis. Differentially expressed genes (DEG) and potential pathways were validated by quantitative reverse transcription polymerase chain reaction, immunoblotting and Masson staining, using additional clinical samples. ResultsTop biological processes in the endometrium of women with versus without adenomyosis, enriched from DEG, comprised inflammation, extracellular matrix (ECM) organization, collagen degradation and hyaluronan synthesis, which are key in cell migration and cell movement. Top biological processes enriched from DEG in the myometrium of women with versus without adenomyosis revealed ECM organization dysfunction, abnormal sensory pain perception and gamma aminobutyric acid (GABA) synaptic transmission. Dysregulation of prolactin signalling was also enriched in eutopic endometrium and in the myometrium of women with adenomyosis. ConclusionsOverall, our results support the invasive endometrium theory in the pathogenesis of adenomyosis, in which inflammation induces ECM remodelling resulting in a track for subsequent endometrial collective cell migration and onset of adenomyosis. Moreover, abnormal myometrial GABA synaptic transmission may contribute to dysmenorrhoea in women with adenomyosis and is a possible target for novel therapeutic development. Prolactin signalling abnormalities may serve as another opportunity for therapeutic intervention.

Basic mechanisms of peripheral nerve injury and treatment via electrical stimulation.

Previous studies on the mechanisms of peripheral nerve injury (PNI) have mainly focused on the pathophysiological changes within a single injury site. However, recent studies have indicated that within the central nervous system, PNI can lead to changes in both injury sites and target organs at the cellular and molecular levels. Therefore, the basic mechanisms of PNI have not been comprehensively understood. Although electrical stimulation was found to promote axonal regeneration and functional rehabilitation after PNI, as well as to alleviate neuropathic pain, the specific mechanisms of successful PNI treatment are unclear. We summarize and discuss the basic mechanisms of PNI and of treatment via electrical stimulation. After PNI, activity in the central nervous system (spinal cord) is altered, which can limit regeneration of the damaged nerve. For example, cell apoptosis and synaptic stripping in the anterior horn of the spinal cord can reduce the speed of nerve regeneration. The pathological changes in the posterior horn of the spinal cord can modulate sensory abnormalities after PNI. This can be observed in cases of ectopic discharge of the dorsal root ganglion leading to increased pain signal transmission. The injured site of the peripheral nerve is also an important factor affecting post-PNI repair. After PNI, the proximal end of the injured site sends out axial buds to innervate both the skin and muscle at the injury site. A slow speed of axon regeneration leads to low nerve regeneration. Therefore, it can take a long time for the proximal nerve to reinnervate the skin and muscle at the injured site. From the perspective of target organs, long-term denervation can cause atrophy of the corresponding skeletal muscle, which leads to abnormal sensory perception and hyperalgesia, and finally, the loss of target organ function. The mechanisms underlying the use of electrical stimulation to treat PNI include the inhibition of synaptic stripping, addressing the excessive excitability of the dorsal root ganglion, alleviating neuropathic pain, improving neurological function, and accelerating nerve regeneration. Electrical stimulation of target organs can reduce the atrophy of denervated skeletal muscle and promote the recovery of sensory function. Findings from the included studies confirm that after PNI, a series of physiological and pathological changes occur in the spinal cord, injury site, and target organs, leading to dysfunction. Electrical stimulation may address the pathophysiological changes mentioned above, thus promoting nerve regeneration and ameliorating dysfunction.

VGF: a biomarker and potential target for the treatment of neuropathic pain?

Neuropathic pain (NP) remains an area of considerable unmet medical need. A persistent challenge in the management of NP is to target the specific mechanisms leading to a change from normal to abnormal sensory perception while ensuring that the defensive pain perception remains intact. Targeting VGF-derived neuropeptides may offer this opportunity. VGF was first identified in 1985 and is highly expressed after nerve injury and inflammation in neurons of both the peripheral and central nervous system. Subsequent studies implicate the vgf gene and its products in pain pathways. This narrative review was supported by a systematic search to identify, select, and critically appraise all relevant research investigating the role of VGF-derived neuropeptides in pain pathways. It predominantly focuses on in vivo investigations of the role of VGF in the initiation and maintenance of NP. VGF expression levels are very low under normal physiological conditions and nerve injury results in rapid and robust upregulation, increasing mechanical and thermal hypersensitivity. The identification of the 2 complement receptors with which VGF neuropeptides interact suggests a novel interplay of neuronal and immune signalling mediators. The understanding of the molecular mechanisms and signalling events by which VGF-derived active neuropeptides exert their physiological actions is in its infancy. Future work should aim to improve understanding of the downstream consequences of VGF neuropeptides thereby providing novel insights into pain mechanisms potentially leading to the identification of novel therapeutic targets.

Functional Alterations of Postcentral Gyrus Modulated by Angry Facial Expressions during Intraoral Tactile Stimuli in Patients with Burning Mouth Syndrome: A Functional Magnetic Resonance Imaging Study.

Previous findings suggest that negative emotions could influence abnormal sensory perception in burning mouth syndrome (BMS). However, few studies have investigated the underlying neural mechanisms associated with BMS. We examined activation of brain regions in response to intraoral tactile stimuli when modulated by angry facial expressions. We performed functional magnetic resonance imaging on a group of 27 BMS patients and 21 age-matched healthy controls. Tactile stimuli were presented during different emotional contexts, which were induced via the continuous presentation of angry or neutral pictures of human faces. BMS patients exhibited higher tactile ratings and greater activation in the postcentral gyrus during the presentation of tactile stimuli involving angry faces relative to controls. Significant positive correlations between changes in brain activation elicited by angry facial images in the postcentral gyrus and changes in tactile rating scores by angry facial images were found for both groups. For BMS patients, there was a significant positive correlation between changes in tactile-related activation of the postcentral gyrus elicited by angry facial expressions and pain intensity in daily life. Findings suggest that neural responses in the postcentral gyrus are more strongly affected by angry facial expressions in BMS patients, which may reflect one possible mechanism underlying impaired somatosensory system function in this disorder.

CNTN6 mutations are risk factors for abnormal auditory sensory perception in autism spectrum disorders

Contactin genes CNTN5 and CNTN6 code for neuronal cell adhesion molecules that promote neurite outgrowth in sensory-motor neuronal pathways. Mutations of CNTN5 and CNTN6 have previously been reported in individuals with autism spectrum disorders (ASDs), but very little is known on their prevalence and clinical impact. In this study, we identified CNTN5 and CNTN6 deleterious variants in individuals with ASD. Among the carriers, a girl with ASD and attention-deficit/hyperactivity disorder was carrying five copies of CNTN5. For CNTN6, both deletions (6/1534 ASD vs 1/8936 controls; P=0.00006) and private coding sequence variants (18/501 ASD vs 535/33480 controls; P=0.0005) were enriched in individuals with ASD. Among the rare CNTN6 variants, two deletions were transmitted by fathers diagnosed with ASD, one stop mutation CNTN6W923X was transmitted by a mother to her two sons with ASD and one variant CNTN6P770L was found de novo in a boy with ASD. Clinical investigations of the patients carrying CNTN5 or CNTN6 variants showed that they were hypersensitive to sounds (a condition called hyperacusis) and displayed changes in wave latency within the auditory pathway. These results reinforce the hypothesis of abnormal neuronal connectivity in the pathophysiology of ASD and shed new light on the genes that increase risk for abnormal sensory perception in ASD.

Arsenic groundwater contamination and its health effects in Patna district (capital of Bihar) in the middle Ganga plain, India

We investigated the extent and severity of groundwater arsenic (As) contamination in five blocks in Patna district, Bihar, India along with As in biological samples and its health effects such as dermatological, neurological and obstetric outcome in some villages. We collected 1365 hand tube-well water samples and analyzed for As by the flow injection hydride generation atomic absorption spectrometer (FI-HG-AAS). We found 61% and 44% of the tube-wells had As above 10 and 50 μg/l, respectively, with maximum concentration of 1466 μg/l. Our medical team examined 712 villagers and registered 69 (9.7%) with arsenical skin lesions. Arsenical skin lesions were also observed in 9 children of 312 screened. We analyzed 176 biological samples (hair, nail and urine). Out of these, 69 people had arsenical skin lesions and rest without skin lesions. We found 100% of the biological samples had As above the normal levels (concentrations of As in hair, nail and urine of unexposed individuals usually ranges from 20 to 200 μg/kg, 20–500 μg/kg and <100 μg/l, respectively), indicating many people are sub-clinically affected. Arsenical neuropathy was observed in 40.5% of 37 arsenicosis patients with 73.3% prevalence for predominant sensory neuropathy and 26.7% for sensor-motor. Among patients, different clinical and electrophysiological neurological features and abnormal quantitative sensory perception thresholds were also noted. The study also found that As exposed women with severe skin lesions had adversely affected their pregnancies. People including children in the affected areas are in danger. To combat As situation in affected areas, villagers urgently need (a) provision of As-safe water for drinking and cooking, (b) awareness about the danger of As toxicity, and (c) nutritious food.

Abnormal tactile pressure perception in Parkinson’s disease

Background/objective: Some of the behavioral disorders associated with Parkinson’s disease (PD), such as the reduced magnitude of actions (hypometria) may be related to an impairment in cognitive disengagement. A reduced ability to disengage attention from previous sensory stimuli will alter perception with a reduced range of estimated stimulus magnitudes (contraction to the mean). To test this disengagement hypothesis, participants with PD were tested to learn whether they had abnormal sensory perception with overestimation of the relative magnitude of weaker tactile stimuli and underestimation of the relative magnitude of stronger tactile stimuli in relation to a reference stimulus. Design/method: The participants were 12 people with PD and 12 healthy adults. Test stimuli were applied to the palm using Semmes–Weinstein monofilaments (SWM) of 6 magnitudes, 3 greater and 3 less than a standard stimulus. In each trial, after being stimulated with the reference (standard) stimulus, a test monofilament was applied, and the participant was asked to provide a numerical estimate of the magnitude of the second stimulus relative to the standard. Results: Compared to the control group, participants with PD overestimated the magnitudes of the tactile stimuli below the standard stimulus and underestimated the magnitudes of stimuli above the standard stimulus. Conclusions: These results demonstrate that people with PD likely have a reduced ability to estimate the relative magnitudes of tactile sensory stimuli. Whereas deafferentation would alter perception in one direction, the impairment of these participants with PD may result from a disorder of disengagement, and disorders of disengagement are often due to frontal-executive dysfunction.

29. Impaired VEP after photostress in migraine patients between attacks

Subtle impaired macular vision was observed among different psychophysical experimental tasks in migraine. Here we studied visual evoked potential (VEP) after photostress (PS) representing an objective index of the dynamic properties of macular performance after exposure to intense light stimulation. We recorded VEPs in basal condition and after PS in 43 migraineurs patients (19 with and 24 without aura) and 14 healthy volunteers (HV). We compared P100 implicit time and N75-P100 amplitude of baseline VEP with those collected every 20 s up to 200 s after PS. In HV, N75-P100 amplitude significantly decreased 20 s after PS, and recovered subsequently. There was no effect in the migraine groups. In fact, the percentage reduction in N75-P100 amplitude observed at 20s after photostress in MO and MA patients were lower than in HV (MO vs HV P < 0.05, MA vs HV P < 0.05). In migraine, the percentage of amplitude change at 20 s was negatively correlated with number of days since the last migraine attack (r = −0.525, p = 0.02). We documented altered recovery after PS under the influence of imminent attack. Whether present VEP findings are related to the ictal/interictal migraineur susceptibility to abnormal sensory perception, such as visual discomfort, remains to be determined.

Abnormal sensory perception or peristaltic dysfunction: which one is associated with symptoms?

Summary The generation of esophageal symptoms while swallowing is a multifactorial phenomenon. Previous studies tried to analyze the correlation between objective esophageal functions using high-resolution manometry (HRM) and abnormal esophageal perceptions such as pain or dysphagia, but they were unable to verify the relationship between them. Recently, Xiao et al 1 investigated whether new manometric metrics can show a relationship between symptoms and abnormal motor function while swallowing. HRM studies included 10 supine liquids, 5 upright liquids, 2 upright viscous and 2 upright solid swallows. All patients evaluated their esophageal symptoms for each upright swallow. Symptoms were graded on a 4-point likert score (0, none; 1, mild; 2, moderate; 3, severe). HRM metrics were compared between groups with and without symptoms during the upright liquid protocol. Of the 269 patients, 116 recorded symptoms during viscous or solid swallows. HRM metrics were similar between swallows with and without associated symptoms in the upright, viscous and solid swallows. No correlation was noted between the HRM metrics and the symptom scores among swallow types. Finally, they concluded that esophageal symptoms are not related to abnormal motor functions defined by HRM. Also, other factors beyond circular muscle contraction patterns should be explored as possible causes of symptom generation.

Functional Dyspepsia in Children

Functional dyspepsia (FD) is a widely prevalent problem in pediatrics, reportedly occurring in 3% to 27% of children and accounting for considerable impact on quality of life and health care costs. FD is defined by the Rome III classification as persistent upper abdominal pain or discomfort, not related to bowel movements, and without an organic cause, that is present for at least 2 months prior to diagnosis. Abnormal sensory perception, motor dysfunction, and psychosocial factors have been implicated in the causation of FD. Hypersensitivity to gastric distension, delayed gastric emptying, antral hypomotility, and gastric dysrhythmia are some abnormalities that have been noted in FD. Diagnosis of FD is based on a thorough history and examination, and an appropriate selection of tests based on clinical judgment, the presence of alarm signs, and response to treatment. A positive diagnosis of FD helps to shift focus from further testing to treatment of symptoms. The majority of children with dyspepsia do not have mucosal lesions on endoscopy; hence, endoscopy is not mandatory for the diagnosis of FD. Helicobacter pylori is an uncommon cause of dyspepsia in children, and test and treat strategy is discouraged. Delayed gastric emptying may be present in up to 70% of children with dyspepsia. A biopsychosocial approach to treatment involving medications, psychological and social supports, and complementary therapies is advocated. Proton pump inhibitors (PPIs) and prokinetics are commonly used first-line medications. PPIs are preferred when epigastric pain is the predominant symptom, whereas prokinetics may be chosen when postprandial fullness or early satiety is the main symptom. PPIs may be more efficacious and cost-effective than H2 blockers according to adult data.

Once more with feeling: Tactility and cognitive alterity, medieval and modern

This essay compares medieval and modern narratives of abnormal sensory perception with a focus on ‘phantom’ tactility. After considering the ways in which tactile perception is represented and managed in recent neuroscientific literature, particularly in Ramachandran and Blakeslee's popular work, Phantoms in the Brain, it turns to an account of extraordinary tactility in the Life of the twelfth-century English anchorite, Christina of Markyate. It argues that the medieval text can point to some of the sensory biases and disabling practices of current medical discourses about abnormal perception.

Alice in Wonderland Syndrome and Lyme Disease

In the 1865 novel, Alice in Wonderland , Alice proclaims it “curiouser and curiouser!” as she grows bigger and expands like a telescope after eating the cake she finds in a rabbit hole. Such distortions of form, size, and movement are characteristic of an abnormal sensory aura or perception termed “metamorphopsia” or “Alice in Wonderland syndrome.”1 Metamorphopsia can occur as a symptom of migraine or frontal lobe epilepsy.2,3 …

Intrinsic Network Connectivity Reflects Consistency of Synesthetic Experiences

Studying cognitive processes underlying synesthesia, a condition in which stimulation of one sensory modality automatically leads to abnormal additional sensory perception, allows insights into the neural mechanisms of normal and abnormal cross-modal sensory processing. Consistent with the notion that synesthesia results from hyperconnectivity, functional connectivity analysis (adopting independent component analysis and seed-based correlation analysis) of resting-state functional magnetic resonance imaging data of 12 grapheme-color synesthetes and 12 nonsynesthetic control subjects revealed, in addition to increased intranetwork connectivity, both a global and a specific (medial and lateral visual networks to a right frontoparietal network) increase of intrinsic internetwork connectivity in grapheme-color synesthesia. Moreover, this increased intrinsic network connectivity reflected the strength of synesthetic experiences. These findings constitute the first direct evidence of increased functional network connectivity in synesthesia. In addition to this significant contribution to the understanding of the neural mechanisms of synesthesia, our results have important general implications. In combination with data derived from clinical populations, our data strongly suggest that altered differences in intrinsic network connectivity are directly related to the phenomenology of human experiences.